EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression.

Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

TM4SF19 aggravates LPS-induced attenuation of vascular endothelial cell adherens junctions by suppressing VE-cadherin expression.

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.

The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: a systematic review and meta-analysis of randomized controlled trials.

Background: Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health. Aims: In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis. Methods: A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence. Results: Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), p < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), p = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), p < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), p < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), p = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), p = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), p < 0.00001] without affecting blood levels of glucose and inflammatory cytokines. Conclusion: Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required. Systematic review registration: PROSPERO, identifier CRD42023438460.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain.

BACKGROUND: Urological calculi often cause renal colic, which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region. Development of methods to quickly relieve these pain symptoms has garnered clinical attention. Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas, and it has good pain-relieving effects. We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety. AIM: To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain. METHODS: Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences, each with 41 cases. The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs, whereas the observation group received pain management nursing and wrist-ankle acupuncture. Subsequently, the pain-relieving effect was compared between the two groups. RESULTS: The score on the visual analog scale (VAS) at 24, 48, and 72 h postintervention was decreased in both groups compared with the baseline data; moreover, the observation group scored significantly lower than the control group on the VAS at each time point after the intervention (P < 0.05). The clinical efficacy at 24 h postintervention was not significantly different between the two groups (P > 0.05). In turn, the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group (P < 0.05). Finally, the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group (P < 0.05). No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups. CONCLUSION: Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate, which was worthy of clinical application.

LncRNA NIPA1-SO confers atherosclerotic protection by suppressing the transmembrane protein NIPA1.

Long non-coding RNAs (lncRNAs) are emerging as important players in gene regulation and cardiovascular diseases. However, the roles of lncRNAs in atherosclerosis are poorly understood. In the present study, we found that the levels of NIPA1-SO were decreased while those of NIPA1 were increased in human atherosclerotic plaques. Furthermore, NIPA1-SO negatively regulated NIPA1 expression in human umbilical vein endothelial cells (HUVECs). Mechanistically, NIPA1-SO interacted with the transcription factor FUBP1 and the NIPA1 gene. The effect of NIPA1-SO on NIPA1 protein levels was reversed by the knockdown of FUBP1. NIPA1-SO overexpression increased, whilst NIPA1-SO knockdown decreased BMPR2 levels; these effects were enhanced by the knockdown of NIPA1. The overexpression of NIPA1-SO reduced while NIPA1-SO knockdown increased monocyte adhesion to HUVECs; these effects were diminished by the knockdown of BMPR2. The lentivirus-mediated-overexpression of NIPA1-SO or gene-targeted knockout of NIPA1 in low-density lipoprotein receptor-deficient mice reduced monocyte-endothelium adhesion and atherosclerotic lesion formation. Collectively, these findings revealed a novel anti-atherosclerotic role for the lncRNA NIPA1-SO and highlighted its inhibitory effects on vascular inflammation and intracellular cholesterol accumulation by binding to FUBP1 and consequently repressing NIPA1 expression.

Suspicious symptom monitoring for leprosy: an optimal practice for early detection under a low endemic situation in Zhejiang Province, China.

BACKGROUND: Leprosy is a chronic infectious disease that causes disabilities and deformities. Early detection is a major strategy for leprosy control. This study reported a new practice of suspicious symptom monitoring for early detection of leprosy. METHODS: A descriptive and comparative analysis between a non-strategy group of pre-implementation of suspicious symptom monitoring in 2005-2011 and a strategy group of strategy implementation in 2012-2018 was conducted through indicators of the number of times of misdiagnoses, delayed period, proportion of early detected cases, and proportion of disabilities. RESULT: Compared with the non-strategy group in 2005-2011, the median number of times of misdiagnoses was decreased from two times to zero times (z = 4.387, P < 0.001), and the median delayed period of newly detected cases were shortened from 24 months to 13 months (z = 2.381, P < 0.001), the proportion of early detected cases was increased from 43.7% to 75.2% (χ2 = 29.464, P < 0.001), the proportion of grade 2 disabilities was decreased from 28.6% in the highest year of 2005 to 4.0% in the lowest year of 2014, and the average proportion of disabilities was decreased from 33.5% to 17.6% (χ2 = 9.421, P = 0.002) in the strategy group in 2012-2018, respectively. CONCLUSION: Suspicious symptom monitoring promoted early detection of cases by reducing the number of times misdiagnosis of leprosy patients, shortening the delayed period, increasing the proportion of early detection, and decreasing the proportion of disabilities. It is an important and recommendable public health strategy for leprosy prevention and control in a low epidemic condition.

Thinning or Opening: A Randomized Sibling-Embryo Pilot Trial on the Efficacy of Two Laser-Assisted Hatching Modes During the Extended Culture of Highly Fragmented Cleavage Embryos.

A randomized sibling-embryo pilot trial investigated whether two ways of laser-assisted hatching result in different blastulation and clinical outcomes after extended in vitro culture process of highly fragmented day-3 cleavage embryos. From 92 couples, a total of 315 highly fragmented day-3 embryos (the fragmentation >25%) were recruited and randomized into laser-assisted zona thinning (LAT, n=157) and opening (LAO, n=158) groups, and then underwent a blastocyst culture in vitro. The main endpoint measurements including blastocyst formation and grading as well as the clinical pregnancy after blastocyst transfer were obtained during the treatment procedure of in vitro fertilization and embryo transfer, and then analyzed with generalized estimating equation (GEE) and/or time-to blastocyst analysis models. A total of 166 day-3 embryos developed into blastocyst stage (52.70%), of which 97 were viable blastocysts (30.79%), and 42 top-quality ones (13.33%). LAT did not have any inferior or superior to LAO in the endpoints of either total, viable, top-quality or hatched blastocyst formation, with the ORs (95%CI) from GEE model as 0.89 (0.55-1.45), 0.71 (0.42-1.21), 1.12 (0.56-2.25) and 0.68 (0.42-1.12) respectively for LAT treatment. And the time-to-blastocyst analysis showed a similar result. Additionally, no difference in clinical outcomes after blastocyst transfer was found between the two groups. The author concluded that when applying the LAHs during the extended culture of highly fragmented embryos, both LAT and LAO can generate a promising clinical outcome, and the LAT operation be equivalent to the LAO. Future well-designed, multiple-center, larger-sample investigations are required to ascertain above conclusion.

Status of maternal serum B vitamins and pregnancy outcomes: New insights from in vitro fertilization and embryo transfer (IVF-ET) treatment.

The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with IVF-ET outcomes. A total of 216 subjects aged <35 year in their first oocyte retrieval cycle were recruited. Blood samples from the participants were collected before the oocyte pick-up procedure, and serum levels of riboflavin, niacin, pantothenic acid, vitamin B6 (including PA and PLP), folate, and methylmalonic acid (MMA) were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Endpoints were classified into three groups according to tertiles (lower, middle, and upper) of each vitamin index, and the association of the serum vitamin status with intermediate and clinical outcomes was analyzed using a generalized estimating equation model. Higher riboflavin levels were associated with elevated probabilities of high-quality embryos, as well as clinical pregnancy after embryo transfer. A greater likelihood of transferable embryos was found in the middle tertile of serum folate. Similarly, a negative correlation of serum MMA, a marker of vitamin B12 deficiency, with high-quality embryos was identified. No significance was observed for other vitamins in terms of all endpoints. Therefore, sufficient levels of pre-conception riboflavin, folate, and vitamin B12 are recommended for successful infertility treatment and pregnancy planning; further evidence is needed to confirm our conclusion.

The patterns of distant metastasis and prognostic factors in patients with primary metastatic Ewing sarcoma of the bone.

BACKGROUND: Ewing sarcoma (ES) of bone is accounting for the second most common type of primary bone cancer in children and adolescents. However, the patterns of distant metastasis (DM) and the effect of the sites of DM on survival outcomes were not investigated. AIMS: This study aimed to investigate the patterns of DM and the prognostic factors related to outcomes in primary metastatic ES of the bone. METHODS: Patients who were diagnosed with primary metastatic ES between 2010 and 2018 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, log-rank tests, and Cox proportional-hazards regression models were used for statistical analyses. RESULTS: We identified 277 patients in this study and 95.3% of them (n = 264) receiving chemotherapy. A total of 371 sites of DM were observed. Lung was the most common distant metastatic site (n = 182, 49.1%), followed by bone (n = 139, 37.5%), distant lymph node (n = 26, 7.0%), liver (n = 14, 3.8%), and brain (n = 10, 2.7%). Three-year cause-specific survival (CSS) was 56.1% in the entire cohort. Older age (hazard ratio [HR] 2.210, P < 0.001) and bone metastasis (HR 1.903, P = 0.002) were the independent prognostic factors associated with inferior CSS. Similar results were found in those with bone-only metastasis (n = 80) or lung-only metastasis (n = 117), which showed that patients with bone-only metastasis had an inferior CSS compared to those with metastases only to the lung (HR 1.926, P = 0.005). CONCLUSIONS: Lung and bone are the most frequently distant metastatic sites in patients with primary metastatic ES of bone. Bone metastasis is an independent risk factor for inferior survival.

Long non-coding RNA RP11-490M8.1 inhibits lipopolysaccharide-induced pyroptosis of human umbilical vein endothelial cells via the TLR4/NF-κB pathway.

BACKGROUND AND AIMS: Pyroptosis is a relatively newly discovered form of programmed cell death that plays an important role in the development of atherosclerosis. Many studies have reported that lncRNAs participated in the regulation of atherosclerosis development. However, the regulatory mechanism of lncRNAs in pyroptosis must be studied further. METHODS: In a previous study, microarray analysis was used to detect the lncRNA expression profile in three human advanced atherosclerotic plaques and three normal arterial intimae. In the present research, in vitro assays were performed to investigate the role of lncRNA RP11-490M8.1 on pyroptosis. The relative gene mRNA and lncRNA expression levels were tested by quantitative real-time PCR, and protein levels were evaluated by western blot analysis. The RNA hybrid structure was analyzed using the DINAMelt server. RESULTS: The lncRNA RP11-490M8.1 was significantly downregulated in atherosclerotic plaques and serum. Lipopolysaccharide (LPS) markedly reduced the expression of lncRNA RP11-490M8.1 and induced pyroptosis by increasingthe mRNA and protein levels of NLRP3, caspase-1, ASC, IL-1ß, and IL-18 in HUVECs. The promotion effects ofLPS on pyroptosis were markedly suppressed by overexpression of lncRNA RP11-490M8.1. In addition, LPS increased the mRNA and protein levels ofTLR4 and NF-κB, which was also markedly offsetby overexpression of lncRNA RP11-490M8.1. CONCLUSIONS: These findings indicated that lncRNA RP11-490M8.1 inhibited LPS-induced pyroptosis via the TLR4/NF-κB pathway. Thus, lncRNA RP11-490M8.1 may provide a therapeutic target to ameliorate atherosclerosis.

Single-Nucleotide Polymorphisms in Genes Predisposing to Leprosy in Leprosy Household Contacts in Zhejiang Province, China.

PURPOSE: Genome-wide association studies (GWAS) have identified multiple genetic variants associated with leprosy. To investigate the single and combined associations between single-nucleotide polymorphisms (SNPs) and the development of leprosy, we therefore performed generalized multi-analytical (GMDR) analysis in Chinese leprosy household contacts and constructed a risk prediction model. PATIENTS AND METHODS: This case-control study included 229 leprosy cases and 233 healthy household contacts in Zhejiang province, China. Participants were genotyped for 17 polymorphisms selected from GWAS. The Pearson χ2 test, logistic regression and GMDR analysis were performed to investigate gene-gene interactions and construct a risk prediction model for leprosy. RESULTS: The genotype and the allele distributions of rs142179458, rs2275606, rs663743 and rs73058713 were significantly different between patients and controls. rs2275606, rs6478108, rs663743 and rs73058713 showed an association after adjusting for sex and age in the logistic regression. A five-way interaction model consisting of rs2058660, rs2275606, rs4720118, rs6478108 and rs780668 was chosen as the optimal model for determining leprosy susceptibility. The model classified 237 (51.3%) into the low-risk group and 225 (48.7%) individuals into the high-risk group. The area under the curve (AUC) of this model was 0.757 (95% CI: 0.712-0.803), and the odds ratio for leprosy between the high- and low-risk groups was 9.733 (95% CI: 6.384-14.960; P<0.001). The sensitivity and specificity of the model were observed to be 74.7% and 76.8%, respectively. CONCLUSION: Our results suggest that rs2058660, rs2275606, rs4720118, rs6478108 and rs780668, five SNPs with a significant sole effect on leprosy, interact to confer a higher risk for the disease in leprosy household contacts (HHCs).

Parthenolide Augments the Chemosensitivity of Non-small-Cell Lung Cancer to Cisplatin via the PI3K/AKT Signaling Pathway.

The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC.

Lipopolysaccharide Promotes Inflammatory Response via Enhancing IFIT1 Expression in Human Umbilical Vein Endothelial Cells.

Atherosclerosis is an immune inflammatory disease and a major cause of mortality and morbidity worldwide. It is generally considered that a number of potent proinflammatory cytokines have a great influence on its pathogenesis, including IL-1ß, IL-6, TNF-α, and NF-κB. A growing amount of empirical evidence indicates that the mechanism of cardiac dysfunction caused by lipopolysaccharide (LPS) is the activation of inflammation, but the exact mechanism in atherosclerosis is still unclear. Previous studies have shown that interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) participates in inflammation, but the effects and possible mechanism of action of IFIT1 on proinflammatory response remain largely unexplained. We found that LPS induced upregulation of IFIT1 expression in a time- and concentration-dependent manner in human umbilical vein endothelial cells (HUVECs). Overexpression of IFIT1 significantly upregulated LPS-induced expression of IL-1ß, IL-6, TNF-α, and NF-κB in HUVECs. IFIT1-siRNA treatment dramatically decreased LPS-induced expression of IL-1ß, IL-6, TNF-α, and NF-κB in HUVECs. The above results show that LPS induces expression of IL-1ß, IL-6, TNF-α, and NF-κB through upregulating IFIT1 expression in HUVECs, and suggested that IFIT1 could act as potential therapeutic target to ameliorate atherosclerosis-related diseases.

MLKL Aggravates Ox-LDL-Induced Cell Pyroptosis via Activation of NLRP3 Inflammasome in Human Umbilical Vein Endothelial Cells.

Atherosclerosis is a progressive chronic inflammation in the arterial walls. It is believed that the deposition of low-density lipoprotein (LDL) and its damage to endothelial cells play a vital role in atherosclerosis. Oxidized LDL (Ox-LDL) was confirmed to induce endothelial cell pyroptosis which plays an important role in intima inflammation and the development of atherosclerosis, but the underlying molecular mechanism needs to be explored. Here, we showed that ox-LDL upregulated the expression of mixed lineage kinase domain-like (MLKL) protein at both the mRNA and protein levels in endothelial cells, associated with the augment of pro-caspase-1 cleavage, interleukin-1ß (IL-1ß) maturation, pro-IL-1ß production, and lactate dehydrogenase (LDH) release. Overexpression of MLKL substantially aggravated ox-LDL-induced increasing levels of caspase-1, IL-1ß, pro-IL-1ß, and LDH. MLKL-induced caspase-1 activation and IL-1ß maturation were abolished by NLR family, pyrin domain-containing 3 (NLRP3) specific inhibitor MCC950, or extracellular high potassium concentration. Our findings indicated that MLKL is essential for regulation of ox-LDL-induced pyroptosis and inflammation through the activation of NLRP3 inflammasome, and suggested that MLKL could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.

Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells.

BACKGROUND AND AIMS: Many clinical trials have demonstrated that statins convey protective effects against atherosclerosis independent of cholesterol-lowering capacities. Other evidence indicates that pyroptosis, a type of programmed cell death, is likely involved in atherosclerosis, but the effects and mechanisms of statins on pyroptosis must be further revealed. METHODS: Here, we explored the effects and mechanisms of atorvastatin on pyroptosis in human vascular endothelial cells by quantitative real-time polymerase chain reaction and Western blot analyses. RESULTS: Atorvastatin upregulated long non-coding RNA (lncRNA) NEXN-AS1 and the expression of NEXN at both the mRNA and protein levels in a concentration- and time-dependent manner. Atorvastatin inhibited pyroptosis by decreasing the expression levels of the canonical inflammasome pathway biomarkers NLRP3, caspase-1, GSDMD, IL-1ß, and IL-18 at both the mRNA and protein levels. The promotion effects of atorvastatin on NEXN-AS1 and NEXN expression could be significantly abolished by knockdown of lncRNA NEXN-AS1 or NEXN, and its inhibitory effects on pyroptosis were also markedly offset by knock-down of lncRNA NEXN-AS1 or interference of NEXN. CONCLUSIONS: These results demonstrated that atorvastatin regulated pyroptosis via the lncRNA NEXN-AS1-NEXN pathway, which provides a new insight into the mechanism of how atorvastatin promotes non-lipid-lower effects against the development of atherosclerosis and gives new directions on how to reverse atherosclerosis.

Damage Detection of Asphalt Concrete Using Piezo-Ultrasonic Wave Technology.

Asphalt concrete has been widely used in road engineering as a surface material. Meanwhile, ultrasonic testing technology has also been developed rapidly. Aiming to evaluate the feasibility of the ultrasonic wave method, the present work reports a laboratory investigation on damage detection of asphalt concrete using piezo-ultrasonic wave technology. The gradation of AC-13 was selected and prepared based on the Marshall's design. The ultrasonic wave velocities of samples were tested with different environmental conditions firstly. After that, the samples were destroyed into two types, one was drilled and the other was grooved. And the ultrasonic wave velocities of pretreated samples were tested again. Furthermore, the relationship between velocity and damaged process was evaluated based on three point bending test. The test results indicated that piezoelectric ultrasonic wave is a promising technology for damage detection of asphalt concrete with considerable benefits. The ultrasonic velocity decreases with the voidage increases. In a saturated water environment, the measured velocity of ultrasonic wave increased. In a dry environment (50 °C), the velocity the ultrasonic waves increased too. After two freeze-thaw cycles, the voidage increased and the ultrasonic velocity decreased gradually. After factitious damage, the wave must travel through or most likely around the damage, the ultrasonic velocity decreased. During the process of three point bending test, the ultrasonic velocity increased firstly and then decreased slowly until it entered into a steady phase. At last the velocity of ultrasonic wave decreased rapidly. In addition, the errors of the results under different test conditions need to be further studied.

Comparative studies on the surface/interface properties and aggregation behavior of mono-rhamnolipid and di-rhamnolipid.

The surface properties of mono-rhamnolipid (Rha-C10-C10, R1) and di-rhamnolipid (Rha-Rha-C10-C10, R2) were investigated after separation and purification. The effects of environmental factors on equilibrium surface tension of these surfactants were studied by changing the temperature, salinity, and pH. Results show that R1 possesses a better surface activity than R2, but both are stable at low pH values and high temperature. Moreover, the diffusion and adsorption processes of R1 and R2 were studied by dynamic surface tension measurements. The initial adsorption processes of R1 and R2 were diffusion-controlled, and the effective diffusion coefficient of R1 was higher than that of R2 at the same concentration. We also monitored the dynamic interfacial tension curves of R1 and R2 with or without aging at high temperature, revealing that both feature high temperature resistance, but R1 exhibited a better interfacial activity than R2. For aggregation behavior in the bulk phase, dynamic light scattering and UV - vis spectrophotometry were used to measure and observe the aggregation of rhamnolipids R1 and R2 at different temperatures and pH values. Results show the vesicle-to-micelle transformation of R1 and R2 aggregates with decreasing pH. This result is attributed to the considerable influence of solution pH to the dissociation degree of rhamnolipids. Thus, pH values significantly influence particle size distribution.

Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN.

Noncoding RNAs are emerging as important players in gene regulation and disease pathogeneses. Here, we show that a previously uncharacterized long noncoding RNA, nexilin F-actin binding protein antisense RNA 1 (NEXN-AS1), modulates the expression of the actin-binding protein NEXN and that NEXN exerts a protective role against atherosclerosis. An expression microarray analysis showed that the expression of both NEXN-AS1 and NEXN was reduced in human atherosclerotic plaques. In vitro experiments revealed that NEXN-AS1 interacted with the chromatin remodeler BAZ1A and the 5' flanking region of the NEXN gene and that it also upregulated NEXN expression. Augmentation of NEXN-AS1 expression inhibited TLR4 oligomerization and NF-κB activity, downregulated the expression of adhesion molecules and inflammatory cytokines by endothelial cells, and suppressed monocyte adhesion to endothelial cells. These inhibitory effects of NEXN-AS1 were abolished by knockdown of NEXN. In vivo experiments using ApoE-knockout mice fed a Western high-fat diet demonstrated that NEXN deficiency promoted atherosclerosis and increased macrophage abundance in atherosclerotic lesions, with heightened expression of adhesion molecules and inflammatory cytokines, whereas augmented NEXN expression deterred atherosclerosis. Patients with coronary artery disease were found to have lower blood NEXN levels than healthy individuals. These results indicate that NEXN-AS1 and NEXN represent potential therapeutic targets in atherosclerosis-related diseases.

A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells.

UNLABELLED: Regulation on the function of the hepatic stellate cells (HSCs) is one of the proposed therapeutic approaches to liver fibrosis. In the present study, we examined the in vitro and in vivo effects of CPU-II2, a novel synthetic oleanolic acid (OLA) derivative with nitrate, on hepatic fibrosis. This compound alleviated CCl4-induced hepatic fibrosis in mice with a decrease in hepatic hydroxyproline (Hyp) content and histological changes. CPU-II2 also attenuated the mRNA expression of alpha-smooth muscle actin (alpha-SMA) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) induced by CCl4 in mice and reduced both mRNA and protein levels of alpha-SMA in HSC-T6 cells. Interestingly, CPU-II2 did not affect the survival of HSC-T6 cells but decreased the expression of procollagen-alpha1 (I) in HSC-T6 cells through down-regulating the phosphorylation of p38 MAPK. CONCLUSION: CPU-II2 attenuates the development of liver fibrosis rather by regulating the function of HSCs through p38 MAPK pathway than by damaging the stellate cells.