Hyaluronan and Glucose Dual-targeting Probe: Synthesis and Application.

In this work, we developed a dual-targeting probe consisted of well-defined hyaluronan (HA) oligosaccharide and glucose (Glc) labeled with Rhodamine B (HGR). The probe was designed to enhance tumor targeting both in vitro and in vivo, by simultaneously targeting CD44 and Glc transporter 1 (GLUT1). The HA oligosaccharide component was crucial for accurately assessing the impact of sugar chain structure on targeting efficacy, while its unoccupied carboxyl groups could minimize interference with HA's binding affinity to CD44. In vitro studies demonstrated that HGR possessed remarkable cytocompatibility and superior targeting abilities compared to single-targeting probes. It displayed a marked preference for CD44high/GLUT1high cells rather than CD44low/GLUT1low cells. In vivo studies using murine models further confirmed the significantly enhanced targeting efficacy and excellent biocompatibility of HGR. Therefore, this designed dual-targeting probe holds potential for clinical tumor detection.

The efficacy of different types of cerebral embolic protection device during transcatheter aortic valve implantation: a meta-analysis.

Aims: Perioperative stroke remains a devastating complication after transcatheter aortic valve implantation (TAVI), and using a cerebral embolic protection device (CEPD) during TAVI may reduce the occurrence of stroke according to some studies. Therefore, we conducted this meta-analysis to determine whether CEPD should be routinely used during TAVI. Methods and results: The inclusion criteria for this study were randomized controlled trials (RCTs) that examined the outcome of stroke with or without CEPD during TAVI, with a minimum follow-up period of 30 days. The primary endpoint was the occurrence of stroke (including both cerebrovascular accidents and death due to cerebrovascular accidents). The risk of stroke was lower in the CEPD group: RR 0.68, 95% CI 0.49-0.96, p = 0.03, I2 = 0%. A subgroup analysis was conducted according to the type of CEPD. The risk of stroke was lower in the I&LCCA (filter cover the innominate and the left common carotid arteries) type CEPD group: RR 0.66, 95% CI 0.49-0.96, p = 0.03, I2 = 36%. However, there was no statistically significant difference in the risk of stroke in the TMCA [filter cover the three major cerebral arteries (innominate, left common carotid, and subclavian arteries)] type CEPD group: RR 0.81, 95% CI 0.36-1.80, p = 0.60, I2 = 0%. Conclusions: In this meta-analysis, the I&LCCA-type CEPD can reduce the risk of stroke within 30 days following TAVI, but the TMCA type cannot.

Boundedness of Complements for Log Calabi-Yau Threefolds.

In this paper, we study the theory of complements, introduced by Shokurov, for Calabi-Yau type varieties with the coefficient set [0, 1]. We show that there exists a finite set of positive integers N, such that if a threefold pair (X/Z∋z,B) has an R-complement which is klt over a neighborhood of z, then it has an n-complement for some n∈N. We also show the boundedness of complements for R-complementary surface pairs.

ZBTB20 Positively Regulates Oxidative Stress, Mitochondrial Fission, and Inflammatory Responses of ox-LDL-Induced Macrophages in Atherosclerosis.

Atherosclerosis (AS) is one of the most serious and common cardiovascular diseases affecting human health. AS is featured by the accumulation of plaques in vessel walls. The pathophysiology of AS is relevant in the low-density lipoprotein (LDL) uptake by macrophages, as well as the conversion of macrophages to foam cells. However, the mechanisms about how macrophages regulate AS have not been fully elucidated. In this study, we aimed to illuminate the roles of ZBTB20 and to excavate the underlying regulative mechanisms of ZBTB20 in AS. The microarray analysis revealed that ZBTB20 was a hub gene in the oxidative stress and inflammatory responses induced by oxidized LDL (ox-LDL) in AS. Correspondingly, our validation studies showed that ZBTB20 increased in either the human atherosclerotic lesion or the ox-LDL-stimulated macrophages. Moreover, the knockdown of ZBTB20 decreased M1 polarization, suppressed the proinflammatory factors, inhibited mitochondrial fission, and reduced the oxidative stress level of macrophages induced by ox-LDL. The mechanistic studies revealed that the ZBTB20 knockdown suppressed NF-κB/MAPK activation and attenuated the mitochondrial fission possibly via regulating the nucleus translocation of NRF2, a pivotal transcription factor on redox homeostasis. Our in vivo studies showed that the sh-ZBTB20 adenovirus injection could reduce the progression of AS in apolipoprotein E-deficient (ApoE-/-) mice. All in all, these results suggested that ZBTB20 positively regulated the oxidative stress level, mitochondrial fission, and inflammatory responses of macrophages induced by ox-LDL, and the knockdown of ZBTB20 could attenuate the development of AS in ApoE-/- mice.

A study on the association of rs7950273 polymorphism in the PDGFD with ischaemic stroke in the Chinese Han population.

BACKGROUND: The association between the platelet-derived growth factor D (PDGFD) gene and atherosclerosis has been widely proven, whereas the relationship between the PDGFD gene and ischaemic stroke remains unconfirmed. AIM: A case-control study was performed to further evaluate the association of the C → G mutation of rs7950273 in the PDGFD gene with ischaemic stroke (IS) in a Chinese Han population. SUBJECTS AND METHODS: This study recruited 3033 cases and 2807 controls from general hospitals in the southern, central and northern areas of China. The MGB probe and Taqman 7900HT Sequence Detection System were applied for genotyping. RESULTS: Genotype was not significantly associated with ischaemic stroke in total. After adjustment for gender, age, BMI, hypertension, diabetes mellitus and smoking, the CG and GG genotypes were still not associated with ischaemic stroke (p = 0.892 and p = 0.582 for CG and GG, respectively). CONCLUSION: This study suggests that the polymorphism of rs7950273 in the PDGFD gene is not associated with ischaemic stroke in the Chinese Han population. Further studies on the gene-gene and gene-environment interactions for the PDGFD gene and ischaemic stroke are needed.

Two novel susceptibility SNPs for ischemic stroke using exome sequencing in Chinese Han population.

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case-control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p < 1 × 10(-8)) and rs17118 in XYLB gene located on chromosome 3p21 (p < 1 × 10(-6)) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR = 2.02, 95 % CI = 1.35-3.03) or rs17118 AA genotype (OR = 1.50, 95 % CI = 1.17-1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR = 2.78, 95 % CI = 1.59-4.86) and in individuals without diabetes (OR = 1.93, 95 % CI = 1.27-2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR = 1.73, 95 % CI = 1.08-2.78) and for individuals without diabetes (OR = 1.52, 95 % CI = 1.17-1.98) or non-smoker (OR = 1.59, 95 % CI = 1.16-2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.

Quercetin prevents cardiac hypertrophy induced by pressure overload in rats.

Inhibition of cardiac hypertrophy leads to a significant reduction in cardiovascular mortality and morbidity. Quercetin is by far the most abundant flavonoid and believed to ameliorate cardiovascular disease. Therefore, we investigated whether quercetin supplementation could attenuate the development of cardiac hypertrophy induced by pressure overload. Three weeks after suprarenal transverse abdominal aortic constriction, heart to body weight (HW/BW) ratio increased compared to the sham group (3.40 +/- 0.06 mg/g versus 2.83 +/- 0.02 mg/g, P<0.001). The quercetin administered group showed complete inhibition of cardiac hypertrophy (2.85 +/- 0.01 mg/g, P<0.001). Malonyldialdehyde production induced by pressure overload was suppressed by quercetin. The activities of extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase, Akt and GSK-3beta were significantly increased with pressure overload and attenuated by quercetin treatment. We conclude that quercetin appears to block the development of cardiac hypertrophy induced by pressure overload in rats and that these effects may be mediated through reduced oxidant status and inhibition of ERK1/2, p38 MAP kinase, Akt and GSK-3beta activities.

[Analysis on forest plant diversity in the Three Gorges Reservoir Area].

The forest resource is rich in the Three Gorges Reservoir Area, according to the investigation data in the area, there are 41 kinds of forest communities, and the trend of the richness index, species diversity index and evenness index is not regular. In the coniferous forest, the trend of the richness index in different layer along the community is shrub > herb > tree. In the evergreen broadleaf forest, the trend is shrub > tree > herb. In the deciduous broadleaf forest, especially the typical Quercus forest, the trend is shrub > herb and tree, but in the herb layer and the tree layer, the trend fluctuates. The trend of the species diversity index is tree < herb and shrub, but in the herb layer and the shrub layer, the trend fluctuates. In other communities, the trend of all indices along the community fluctuates too. One reason may be the different natural environment and different growth condition of the community, and the long time strong disturbance of the human population is another important factor that couldn't be ignored.