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Abstract Background Platelet activation plays a crucial role in the pathogenesis of coronary artery disease (CAD). Platelet P-selectin (CD62P) is a classic platelet activation indicator on the platelet surface, and soluble TREM-like transcript-1 (sTLT-1) is a new indicator. However, the relationship between these two markers and CAD, especially in acute coronary syndrome (ACS), has not been elucidated. This study aimed to investigate CD62P expression on the platelet surface and sTLT-1 expression in serum, as well as to assess their relationship with CAD. Methods We measured the levels of CD62P and sTLT-1 in 83 patients with CAD compared to 49 controls. The association of these indicators with age, blood pressure, lipid profile, body mass index, and liver injury marker level were also examined. Results CD62P concentration was higher in CAD patients than in the control group (P

Cardiovascular disease is the leading cause of death worldwide, with an annual mortality incidence predicted to rise to 23.3 million worldwide by 2030. Synthetic vascular grafts as an alternative to autologous vessels have shown satisfactory long-term results for replacement of large- and medium-diameter arteries, but have poor patency rates when applied to small-diameter vessels. Nanoparticles with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli- response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made possible their use for improving engineered tissues. Poly (styrene-block-butadiene-block-styrene) (SBS) is a kind of widely used thermoplastic elastomer with good mechanical properties and biocompatibility. Here, we synthesized anthracene-grafted SBS (SBS-An) by the method for the fabrication of a biomimetic elastic membrane with a switchable Janus structure, and formed the patterns on the surface of SBS-An under ultraviolet (UV) light irradiation. By irradiating the SBS-An film at different times (0, 10, 20, 30, 60, and 120 s), we obtained six well-ordered surface-patterned biomimetic elastic film with SBS-An at different heights in the thickness direction and the same distances of intervals (named sample-0, 10, 20, 30, 60, and 120 s). The structural effects of the SBS-An films on the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) were studied, and the possible mechanism was explored. When the HUVECs were cultured on the SBS-An films at different heights in the thickness direction, the sample-30 s with approximately 4 μm height significantly promoted adhesion of the HUVECs at the early stage and proliferation during the culture period compared with the samples of the lower (0, 10, and 20 s) and higher (60 and 120 s) heights. Consistent with this, the sample 30 s showed a higher stimulatory effect on the proliferation- and angiogenesis-related genes. These results suggest that SBS-An with appropriate height could efficiently control bioactivities of the biomimetic elastic membrane and might have great potential in vascular tissue engineering application.

An antimicrobial peptide, known as V13K, was utilized as the framework to study the effects of charge, hydrophobicity and helicity on the biophysical properties and biological activities of α-helical peptides. Six amino acids (Lys, Glu, Gly, Ser, Ala, and Leu) were individually used to substitute the original hydrophobic valine at the selected sixteenth location on the non-polar face of V13K. The results showed that the single amino acid substitutions changed the hydrophobicity of peptide analogs as monitored by RP-HPLC, but did not cause significant changes on peptide secondary structures both in a benign buffer and in a hydrophobic environment. The biological activities of the analogs exhibited a hydrophobicity-dependent behavior. The mechanism of peptide interaction with the outer membrane and cytoplasmic membrane of Gram-negative bacteria was investigated. We demonstrated that this single amino acid substitution method has valuable potential for the rational design of antimicrobial peptides with enhanced activities.

Abstract Patients with Type 2 diabetes mellitus(T2DM) typically have an average or higher bone mineral density (BMD) but are at a significantly higher risk of fracture than patients without diabetes. Trabecular bone score (TBS) is a textural index derived from pixel gray-level variations in lumbar spine DXA image, which has been introduced as an indirect measure of bone quality. This study aimed to discuss the trends and annual rates of change in BMD and TBS with age in Chinese men with T2DM and men without diabetes mellitus. Lumbar spine(LS) TBS was significantly lower in males with T2DM compared to men without diabetes(1.279 ± 0.117 vs. 1.299 ± 0.090, P = 0.005). However, TBS in men with T2DM peaked around age 60, which occurred later and was lower than the peak observed in men without diabetes, who reached their peak TBS around age 50 (1.294 ± 0.126 vs. 1.328 ± 0.088). Femoral neck, total hip, and lumbar spine BMD in men with T2DM were not significantly different from those in men without diabetes. The results showed that both men with or without T2DM exhibited the lowest annual rates of change in TBS at 66–75 years of age, with values of -1.05%(P

Abstract Objectives This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. Methods We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. Findings We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T‐cell related markers, including CD3, CD4, CD8, CD45RO; B‐cell related markers, such as CD11c and CD20; and dendritic cell‐related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor‐infiltrating lymphocytes. Conclusion The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high‐quality and multicenter clinical studies need to be conducted.

Research has identified volatility transmission from the oil market to the tanker freight market through external shocks. However, in the presence of intricate nonlinear structures, the academic literature often encounters difficulties in identifying cycles and their correlations across various timescales. This paper provides a multi-market analysis to comprehend the information from shock effects on different tanker routes and multi-peak fitting. Under different shock regimes, crude oil market and tanker freight rate shocks could transit bi-directly. When events occur, the crude oil market prices the expectations. However, when the actual performance of the future market differs from the traders’ predictions of the future market, a price gap exists. Generally, the trade opportunity is tough to catch up on because only partial information can be found. In this study, we investigate the volatility connection of multi-markets and shock effects to clarify previously undisclosed information using multi-peak analysis. The information gathered and double-checked by cargo markets, crude oil supply-demand balance, and tanker freight prices of various tanker types could assist us in identifying prospective trends and investment opportunities. The volatility of each market, as well as the correlation of multi-markets, gives insights to crude oil dealers, tanker market participants, and energy regulators.

Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a common hematopoietic malignancy, and platelet transfusion plays a crucial role in its treatment. This study aimed to investigate the changes in inflammatory response and autophagy during the preservation of apheresis platelets (AP) and their correlation with platelet transfusion refractoriness (PTR) in ALL. ALL patients were included, and APs were categorized based on the preservation period (day 0, day 1, days 2-3, and days 4-5). The activation factors procaspase-activating compound 1 (PAC-1) and P-selectin (CD62P), AP aggregation function, inflammation levels (interleukin 1 beta [IL-1β], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α] and NOD-like receptor thermal protein domain associated protein 3 [NLRP3]), and autophagy-related genes (p62) during AP preservation were assessed. Following co-culturing APs with peripheral blood mononuclear cells (PBMCs), specific activation markers were studied to observe APs influence on immune cells activation. The effectiveness of platelet transfusion was assessed, and risk factors for PTR were analyzed. As the storage duration of AP increased, the activation factors, coagulation factor activity, inflammation levels, and the activation of immune cells in AP increased, while fibrinogen levels and AP aggregation function decreased. The expression levels of autophagy-related genes (the autophagy marker light chain 3B gene [LC3B] and Beclin 1 gene) decreased with prolongation preservation. The effective rate of AP transfusion in ALL patients was 68.21%. AP preservation time, IL-6, p62, and Beclin 1 were identified as independent risk factors affecting PTR in ALL patients. In conclusion, during AP preservation, inflammation, autophagy, and activation of immune cells were observed to increase. AP preservation time, IL-6, p62, and Beclin 1 were independent risk factors for PTR.

Contractors play a crucial role in ensuring efficient innovation within construction projects but limited research has focused on the innovation capability of contractors. This study utilizes a multi-method approach, including case studies, surveys, and interviews to collect data for analysis. Based on this, a conceptual model is proposed and a simulation mode which utilizes agent-based modeling (ABM) is constructed. ABM is the microscopic bottom-up approach which can describe and follow the agents and interactions. This study proposes a novel conceptual model to examine the emergence of contractor innovation capability at the project level, from a knowledge flow perspective. It fills the research gap regarding innovation capability in temporary cross-organizational projects. Additionally, an ABM simulation model is developed considering project and participant characteristics, providing insights into the formation rule and development mechanisms of contractors’ innovation capability at the project level. The conclusions are as follows: (1) The demand for innovation drives the innovative behavior of different entities within the project. (2) Knowledge availability in public domains and other entities’ knowledge creation capability provide critical support for contractor innovation. (3) Contractors’ capability to absorb and integrate knowledge serves as the foundation for achieving innovation. (4) When contractors possess strong capabilities, effective synergy among organizations facilitates the generation of innovative outcomes.

Abstract The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 μg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 μg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.

Abstract Background Hepatic stellate cell (HSC) activation plays a pivotal role in hepatic inflammation and liver fibrosis. TLR4 pathway activation has been reported to be involved in mice liver fibrosis induced by hepatitis virus infection, alcohol abuse, biliary ligation, carbon tetrachloride 4 treatment, and Schistosoma japonicum (Sj) infection. The effect and mechanisms of the cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear. Methods Mice liver fibrosis were induced by cutaneous infection of Sj cercariae. COX-2 inhibitor, NS398 were injected from week 5 to week 7, while TLR4 inhibitor TAK242 were injected from week 4 to week 8 post Sj infection. Human HSCs line, LX-2 cells were cultured and exposed to LPS or synthetic PGE2, or pretreated by TAK242, TLR4-siRNA or NS398. Liver tissue and serum or in vitro cultured cell lysaste were collected at indicated time courses for exploring the relationship between TLR4 and COX2-PGE2 axis through qPCR, western blot, immunohistochemical assay, ect. One-way analysis of variance among multiple groups followed by Uncorrected Fisher’s LSD-t test or paired comparisons through t test were performed to tell the statistical differences. Results This study investigated the link between the COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culture of HSC strain-LX-2. The COX2/PGE2 axis was positively associated with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis in Sj-infected mice and in lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated cultured HSCs through upregulation of alpha smooth muscle actin (α-SMA) expression. In LPS-triggered HSCs, NS398, a COX2 inhibitor, led to suppression of PGE2 synthesis and reduced expression of α-SMA and type I collagen (COL I). Conclusions These results indicate firstly the positive association of the COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may at least partially control the COX2/PGE2 axis in Sj-infected mice liver and in vitro cultured HSCs. The COX2/PGE2-EP2/EP4 axis might be a good drug target against liver fibrosis induced by Sj infection. Graphic abstract

BackgroundParkinson’s disease (PD) is a multifactorial degenerative disease of the central nervous system, which affects mostly older adults. To date, research has focused on the progression of PD. Simultaneously, it was confirmed that the imbalances in gut microbiota are associated with the onset and progression of PD. Accurate diagnosis and precise treatment of PD are currently deficient due to the absence of effective biomarkers.MethodsIn this study, the pharmacodynamic study of cyanidin-3-O-glucoside in PD mice was used. It intends to use the “imbalance” and “balance” of intestinal microecology as the starting point to investigate the “gut-to-brain” hypothesis using metabolomic-combined 16S rRNA gene sequencing methods. Simultaneously, metabolomic analysis was implemented to acquire differential metabolites, and microbiome analysis was performed to analyze the composition and filter the remarkably altered gut microbiota at the phylum/genera level. Afterward, metabolic pathway and functional prediction analysis of the screened differential metabolites and gut microbiota were applied using the MetaboAnalyst database. In addition, Pearson’s correlation analysis was used for the differential metabolites and gut microbiota. We found that cyanidin-3-O-glucoside could protect 1-methyl-4-phenyl-1,2,3,6− tetrahydropy ridine (MPTP)-induced PD mice.ResultsMetabolomic analysis showed that MPTP-induced dysbiosis of the gut microbiota significantly altered sixty-seven metabolites. The present studies have also shown that MPTP-induced PD is related to lipid metabolism, amino acid metabolism, and so on. The 16S rRNA sequencing analysis indicated that 5 phyla and 22 genera were significantly altered. Furthermore, the differential gut microbiota was interrelated with amino acid metabolism, and so on. The metabolites and gut microbiota network diagram revealed significant correlations between 11 genera and 8 differential metabolites.ConclusionIn combination, this study offers potential molecular biomarkers that should be validated for future translation into clinical applications for more accurately diagnosing PD. Simultaneously, the results of this study lay a basis for further study of the association between host metabolisms, gut microbiota, and PD.

Abstract Background Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established. Results This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection. Conclusions These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.

Thermoplastic polyurethane (TPU)/organoclay nanocomposites are prepared through a melt extrusion process. The TPU is combined with four differently modified organoclays, namely, I.28E, I.30P, I.34TCN, and I.44P. Wide-angle X-ray diffraction and transmission electron microscopy results show that the addition of I.34TCN and I.30P to TPU/organoclay nanocomposites results in the nearly exfoliated structures of the nanocomposites. Addition of I.28E leads to partially intercalated nanocomposites, whereas I.44P cannot disperse effectively in the nanocomposites. Organoclay can enhance the mechanical and gas barrier properties of TPU. The enhancement follows the order TPU/I.34TCN ≥ TPU/I.30P > TPU/I.28E > TPU/I.44P, which is consistent with the degree of dispersion and exfoliation of silicate layers. In addition, Fourier transform infrared absorption spectra show that more hydrogen bonding sites are introduced between the clay modifiers and TPU chains in the TPU/I.34TCN and TPU/I.30P nanocomposites; this has a positive impact on the dispersion of the organoclay and, consequently, the mechanical and gas barrier properties of the nanocomposites. [ABSTRACT FROM AUTHOR]

Background: Fast-onset antidepressants are urgently needed. Chaihu-jia-Longgu-Muli-tang (CLM), a classic Chinese herbal medicine, has been used for antidepressant treatment with long history. Olfactory bulbectomization (OB) model is validated for identification of rapid antidepressant efficacy. Here we used OB model for investigating the rapid onset activity of CLM in mice, and also tested the involvement of prefrontal Akt-mTOR and associated AMPA/NMDA receptors as well as hippocampal BDNF in the rapid antidepressant-like effect of CLM.Methods: The OB model was first characterized with depression-like behaviors and the time course changes of the behaviors. The fast onset of antidepressant effect of CLM was evaluated using sucrose preference test, tail suspension test and forced swim test in OB mice after a single administration. The expression of synaptic proteins of AMPA and NMDA subunits as well as Akt/mTOR signaling in the prefrontal cortex, and hippocampal BDNF was evaluated with the immunoblotting method.Results: A single dose of CLM significantly improved the deficiency in the sucrose preference and decreased the immobility time in the tail suspension test in OB mice. In the prefrontal cortex (PFC) in OB mice, there was lower expression level of the AMPA receptor subunit GluR1, rescued by a single dose of CLM. Additionally, the expression of NMDA subunit NR1 was up-regulated in OB mice, whereas mTOR and its upstream Akt signalings were both down-regulated. These deficiencies were reversed by a single dose of CLM. The CLM treatment also attenuated the expressions of NMDA receptor subunits NR2A and NR2B, which did not change in OB mice. In the hippocampus, expressions of GluR1 and brain derived neurotrophic factor (BDNF) were both up-regulated in OB mice, although CLM increased GluR1, but not BDNF.Conclusion: CLM elicited rapid antidepressant-like effects in the OB model mice, and CLM reversal of the abnormality in PFC expression of AMPA and NMDA receptors and associated Akt-mTOR signaling may underlie the effects.

Stability criterion and its calculation are the crucial issue in the application of sail-assisted ship. How- ever, there is at present no specific criterion and computational methods for the stability of sail-assisted ship. Based on the stability requirements for seagoing ships, the stability criterion of the sail-assisted ships is suggested in this paper. Furthermore, how to calculate the parameters and determine some specific coefficients for the ship stability calculation, as well as how to redraw stability curve are also discussed in this paper. Finally, to give an illustration, the proposed method is applied on a sail assisted-ship model with comments and recommendations for improvement.

Liver fibrosis induced by Schistosoma japonicum (Sj) infection is characterized by the accumulation of extracellular matrix (ECM). The activated and differentiated hepatic stellate cells (HSCs) are the predominant ECM-producing cell type in the liver. Toll-like receptor (TLR) 4 pathway activation plays a key role in mice liver fibrosis models induced by alcohol, biliary ligation, and carbon tetrachloride 4. In this work, we found that TLR4 pathway activation correlated with the severity of liver fibrosis post Sj infection. The TLR4 receptor inhibitor TAK242 reduced the extent of liver fibrosis. The increased expression of TLR4, α-smooth muscle actin (α-SMA), and cytoglobin was observed in the HSCs of mouse liver after Sj infection. In response to stimulation with either lipopolysaccharide or Sj’s soluble egg antigen (SEA), high levels of TLR4 and α-SMA were induced in HSCs and were inhibited by TAK242 treatment. In previous work, we had reported that a high level of transglutaminase 2 (TGM2) is crucial for liver fibrosis post Sj infection. Herein, we found that TLR4 signaling also controlled Tgm2 expression. Inhibition of TGM2 activity by cystamine (CTM) in Sj-infected mice or in HSCs induced with all-trans-retinoic acid (ATRA) stimulation led to a lowered activation of TLR4 signaling and a reduced α-SMA expression. These results were confirmed by downregulating the Tgm2 gene by specific siRNA. These observations implied the presence of a positive feedback regulation between TGM2 and TLR4 signaling in HSCs that correlated with liver fibrosis post Sj infection. This novel connection between TGM2 and TLR4 pathway activation in liver fibrosis induced by Sj infection enhances our understanding of liver diseases.

Recently, the worldwide demand for romaine lettuce (Lactuca sativa L.) has been increasing. Thus, regulation measures of supplementary or shading light are often used in the production of lettuce in some regions. However, inconsistent results on the light saturation point of lettuce from previous studies do not facilitate the regulation of light intensity. In the present study, the effects of different light intensities on anti-oxidative enzyme activity, yield and quality of lettuce were investigated. The results reveal the following: (1) judged by the dynamics of anti-oxidative enzyme activity, there was no light stress to occurr in the 100, 200 and 400 μmol/m2s treatments, a mild light stress occurred in the 600 μmol/m2s treatment, and a serious light stress occurred in the 800 μmol/m2s treatment; (2) increased light intensity gradually reduced the contents of soluble protein and nitrate in lettuce, whereas the content of soluble sugar remarkably increased. The biomass of a single plant of lettuce in the 600 µmol/m2streatment was the highest and second highest in the 400 µmol/m2streatment but was the lowest in the 100 µmol/m2s treatment. No significant difference in the biomass of single plant was observed between the 400 and 600 µmol/m2s treatments. Based on these results, the range of 400 µmol/m2s to 600 µmol/m2s is a recommendablelight intensity for lettuce production.

Transforming growth factor (TGF-β1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-β1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-β1 and TGF-β1 source and its correlation with liver fibrosis after Sj-infection. TGF-β1 was upregulated at weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice. TGF-β1 showed positive staining in liver containing Sj adult worms and eggs. TGF-β1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms’ culture medium. The TGF-β1 mature peptide cDNA sequence and its extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as template, and sequence is analyzed and loaded to NCBI GenBank (number GQ338152.1). TGF-β1 transcript in Sj eggs was higher than in adult worms. In Sj-infected liver, transcriptional level of TGF-β1 from Sj, but not mouse liver, correlated with liver fibrosis extent. This study provides evidence that tTG regulates TGF-β1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis.