Small radius curved sections of two-lane secondary highways have low technical indicators, complex alignments, and frequent accidents. In order to improve the safety of traffic operation, the article ...investigates the curved sections of two-lane secondary highways with different radii and obtains the travelling speeds of different vehicle types at different section locations. By studying the trajectory characteristics and speed characteristics of vehicles travelling in curves, the velocity difference ratio, which responds to the continuity of driving speed, was defined. Then, based on this, this paper investigates the vehicle motion law of small radius curved road sections. The results show that the speed change of large cars in small radius curves is similar to a “U" shape, while the speed change of small cars is similar to a “V" shape. The speed adjustments of the larger cars occur mainly within the range of gentle curves, whereas the speed changes of the smaller cars are large throughout the range of curves. There is a significant exponential function relationship between curve radius and 85 % percentile speed, from which the curve radius threshold can be predicted. This provides a basis for engineering construction of curved road sections and optimization of curve design indicators, which greatly improves the traffic safety level of curved road sections.
The spacing of PVDs is an essential factor affecting the consolidation effect of vacuum preloading. For exploring the influence of spacing of PVDs on the impact of sludge drainage consolidation, ...FeCl3, a commonly used inorganic coagulant, was used to pretreat the sludge. In the experiment a vacuum filtration test was carried out to determine the optimal addition amount of FeCl3, and then the landfill sludge was pretreated according to the FeCl3 optimal addition amount. And two different spacing of PVDs were used to carry out a vacuum preloading contrast test. Then, the drainage and settlement were recorded, and water content and vane shear strength (VSS) were measured after the experiment. Finally, Mercury intrusion porosimetry (MIP) was carried out to explore the pore characteristics of the sludge further. The main conclusions are as follows: After conditioning by FeCl3, the sludge’s flocculent structure was destroyed, the intracellular water was released, and the effect of drainage capacity was significantly improved. After the spacing of PVDs is halved, the average volume reduction ratio and shear strength increases, and the effect of advanced dewatering and volume reduction of sludge improved significantly, leading to a better consolidation effect. In the progress of vacuum drainage consolidation, halving the spacing of PVDs results in large pores transformation into small pores, and the range of drainage consolidation is greatly expanded.
HAPs, similar to Heme Activator Proteins (HAP) or nuclear factor-Y (NF–Y) in yeast and animals, play versatile roles in plant growth, development, and responses to environmental cues.
HAP3b in ...Arabidopsis is a member in the
HAP3 gene family and is involved in regulating flowering time through the long-day photoperiod pathway (Cai et al., 2007, Plant Physiol 145: 98–105). In this study, we report that overexpression of
HAP3b enhances primary root elongation. Detailed analysis showed that
HAP3b-overexpression did not affect the length of the root elongation zone and the cell length profiles in the elongation zone. Kinematic analysis indicated that root cells in
HAP3b-overexpressors elongate faster than the cells in wild-type roots. Using GUS as a reporter gene, we showed that
HAP3b is specifically expressed in the tip region of the root, where cell division and elongation occur. Our results provide evidence to support a role of
HAP3b in regulation of root growth.
►
HAP3b is a putative transcription factor and was previously reported to have a role in regulating flowering time in Arabidopsis. ► Overexpression of
HAP3b enhances primary root elongation in Arabidopsis. ► Overexpression of
HAP3b did not alter the length of root elongation zone and the cell length profile. Thus, overexpression of
HAP3b stimulates both cell division and elongation in the root. ► A role of
HAP3b in controlling root elongation was supported by its tissue expression pattern. It is expressed in the root, specifically in the cell division and elongation region.
Intracranial aneurysm (IA) is one of the most challenging cerebrovascular lesions for clinicians. The aim of this study was to investigate the abnormal expression and role of histone deacetylase 9 ...(HDAC9) in IA-associated injury of vascular endothelial cells (VECs). First, IA tissue and normal arterial tissue were collected and VECs were isolated from IA patients. The expression levels of HDAC9, microRNA (miR)-34a-5p, and vascular endothelial growth factor-A (VEGFA) were determined. Cell viability, proliferation, apoptosis, and migration were assessed by Cell Counting Kit-8 (CCK-8) assay, EdU staining, TUNEL staining, and transwell assay. The binding of miR-34a-5p to VEGFA was analyzed by the dual-luciferase assay, and the accumulation of HDAC9 and lysine histone acetylation at H3 (H3K9, H3K14, and H3K18) on the miR-34a-5p promoter was detected by the chromatin immunoprecipitation assay. The results showed that HDAC9 and VEGFA were increased and miR-34a-5p was decreased in IA tissues and cells. Silencing of HDAC9 inhibited apoptosis and increased viability, proliferation, and migration of VECs, whereas overexpression of HDAC9 exerted the opposite functions. HDAC9 accumulated at the miR-34a-5p promoter to decrease miR-34a-5p expression by reducing H3 locus-specific acetylation and further promoted VEGFA expression. Knockdown of miR-34a-5p or VEGFA overexpression reversed the protective role of HDAC9 silencing in VECs injury. In conclusion, our study suggests that HDAC9 may be a therapeutic target for IA.
Fenofibrate, as a lipid-lowering drug, has been reported to have a protective effect on the retina independent with plasma lipid levels. This study aimed to investigate that the ameliorative effects ...of fenofibrate on systemic and retinal inflammation, as well as gut microbiota dysbiosis in high-fat diet (HFD)-induced mice. C57BL/6J mice were randomly allocated into four groups: standard diet (SD) group; HFD group; SD plus fenofibrate (SD_ Fe) group; HFD plus fenofibrate (HFD_ Fe) group. After successfully establishing models (5 months), indicators associated with lipid, gut barrier, inflammation and gut microbiota were investigated. Our results showed that supplementing the HFD with fenofibrate decreased body weight gain, alleviated dyslipidemia and reversed the downregulation of short-chain fatty acid (SCFAs) in serum, retina and feces. Fenofibrate ameliorated intestinal barrier function damage in HFD-induced mice. Fenofibrate coadministration inhibited the levels of inflammatory factor and lipopolysaccharide (LPS) in the serum and attenuated inflammatory response in the retina of HFD-induced mice. Systemic LPS was positively correlated with a series of inflammatory factors in serum and retina, respectively. Fenofibrate supplementation down-regulated the abundances of LPS-associated bacteria in HFD mice, including
Firmicutes
and
Proteobacteria
at the phylum level,
Desulfovibrionaceae
at the family level, as well as
unclassified_ Desulfovibrionaceae
,
Acetatifactor
,
Flavonifractor
,
Oscillibacter
and
Anaerotruncus
at the genus level. However, fenofibrate treatment up-regulated the abundances of SCFA-associated bacteria in HFD mice, including
Bacteroidetes
at the phylum level,
Porphyromonadaceae
at the family level, as well as
unclassified_Porphyromonadaceae
,
Barnesiella
,
Alloprevotella
and
Bifidobacterium
at the genus level. In conclusion, our results confirmed fenofibrate could attenuate HFD-induced systemic and retinal inflammation, accompanying with restoration of intestinal barrier damage and modulation of gut microbiota/metabolites. This work provided an explanation for the ameliorative effects of fenofibrate on HFD-induced systemic and retinal inflammation might be partially related with the modulation of gut microbiota and its metabolites.
Metastasis‐associated in colon cancer‐1 (MACC1) is a newly identified oncogene, and little is known about its role in gastric cancer (GC). Our study was performed to investigate whether MACC1 ...influences the prognosis of GC patients and to explore the potential mechanisms involved. MACC1 expression was verified to be higher in GC tissues than in adjacent nontumorous tissues by Western blotting. A retrospective analysis of 361 GC patients (Stages I–IV) revealed that higher MACC1 expression was associated with more advanced disease, more frequent postoperative recurrence, more metastases and a higher mortality rate. The disease‐free survival of Stage I–III patients and overall survival of Stage‐IV patients were significantly worse when their tumors showed high MACC1 expression. To investigate the underlying mechanisms, MACC1 overexpression and downregulation were established in two GC cell lines (BGC‐823 and MKN‐28 cells). MACC1 overexpression significantly accelerated tumor growth and facilitated metastasis in athymic mice. MACC1 also promoted the proliferation, migration and invasion of both GC cell lines. Moreover, gastric MACC1 mRNA expression levels were significantly correlated with markers of the epithelial‐to‐mesenchymal transition (EMT) in patients with GC. MACC1 overexpression upregulated mesenchymal–epithelial transition factor and induced changes to markers of EMT, whereas silencing of MACC1 reversed all these changes. These findings provide some novel insights into the role of MACC1, a gene that contributes to a poor prognosis of GC by promoting tumor cell proliferation and invasion as well as the EMT.
What's new?
The oncogene metastasis‐associated in colon cancer‐1 (MACC1) has been reported to promote the progression of colorectal and pancreatic cancers, though whether it has a similar role in gastric cancer has remained uncertain. Here, MACC1 is demonstrated to be closely associated with progression, recurrence, metastasis, and mortality of gastric cancer in patients. It was also found to stimulate growth and metastasis of gastric tumors in athymic mice, to promote proliferation and invasion in gastric cancer cells, and to modulate the epithelial‐to‐mesenchymal transition. The findings suggest that MACC1 may be a novel prognostic indicator for gastric cancer.
Monocyte exhaustion characterized by immune-suppressive features can develop during sepsis and contribute to adverse patient outcomes. However, molecular mechanisms responsible for the establishment ...of immune-suppressive monocytes with reduced expression of immune-enhancing mediators such as CD86 during sepsis are not well understood. In this study, we identified that the TLR4 intracellular adaptor TRAM plays a key role in mediating the sustained reduction of CD86 expression on exhausted monocytes and generating an immune-suppressive monocyte state. TRAM contributes to the prolonged suppression of CD86 through inducing TAX1BP1 as well as SARM1, collectively inhibiting Akt and NFκB. TRAM deficient mice are protected from cecal slurry-induced experimental sepsis and retain immune-competent monocytes with CD86 expression. Our data reveal a key molecular circuitry responsible for monocyte exhaustion and provide a viable target for rejuvenating functional monocytes and treating sepsis.
Obtaining accurate axial length (AL) is very important for the establishment of animal models of myopia. The purpose of this study is to compare the accuracy of Quantel A-B scan, OD-1 A scan, and ...vernier caliper in measuring AL in Sprague Dawley (SD) rats.
In total, 60 5-week-old SD rats were divided into female rat group (
= 30) and male rat group (
= 30). Quantel A-B scan and OD-1 A scan were, respectively, used to measure the AL of both eyes of each living rat, and vernier caliper was used to measure the anterior-posterior diameter of each rat's eyeball. Besides, the correlation between refractive error (RE) and AL measured by different instruments was evaluated, and the accuracy of the three measurement methods was compared according to gender and left/right eyes.
There were significant differences in AL and diopter of SD rats at the same age (
< 0.05). the AL of male rats was greater than that of female rats, while diopter (D) was the opposite; There was no significant difference in AL and D between left and right eyes in the same SD rats (
> 0.05); There were statistical differences among the three measurement methods (
< 0.05), AL measured by vernier caliper was the largest, followed by Quantel A-B scan, OD-1 A scan; Difference in AL between male and female was not statistically significant between the results obtained by Quantel A-B scan and vernier caliper (
> 0.05), but there were statistically significant differences between the other two measurement methods (
< 0.05).
Sex is the influencing factor of AL and RE. Imaging measurement can accurately measure the AL in living small rodents. Compared with OD-1 A scan, Quantel A-B scan may be more accurate.
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•Two alkaloids, and thirteen polyphenols were tentatively identified in bee pollen (BP) extract.•BP extract restored intestinal barrier function against DSS-induced enterocyte ...damage.•BP extract regulated the key metabolites involved in glycerophospholipid metabolism.•BP possessed great therapeutic potential throughout the early stages of DSS-induced colitis.
Bee pollen (BP) is a natural medicine from the hive with various potential health-promoting benefits, but until now there is no study to determine its protective roles in inflammatory bowel disease (IBD). The aim of this study was to reveal the in vitro gastrointestinal protective effects of BP against IBD using molecular and metabolic methods. Dextran sulfate sodium (DSS) challenged Caco-2 cell monolayers were applied to mimic intestinal epithelial cell dysfunctions and metabolic disorders. The pretreatment with BP extract rich in polyphenols ameliorated DSS-induced cell viability losses. It also exerted protective effects against intestinal barrier impairment by strengthening epithelial integrity and tight junction losses induced by DSS. BP up-regulated anti-oxidant (NQO1, Txnrd1, Nrf2) and down-regulated inflammatory (TNF-α and IL-6) mRNA expressions, in accompany with MAPK signaling inhibition. Furthermore, metabolomics analysis based on UPLC-Q-TOF/MS revealed that BP, and DSS treated Caco-2 cells have different metabolomic profiles, with significant changes on key metabolites involved in glycerophospholipid metabolism. Our results showed that BP has great therapeutic potential throughout the early stages of DSS-induced colitis.
Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, ...the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time-dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5′adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)- Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3 (LC3), Sequestosome 1 (p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5′adenosine monophosphate-activated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH-mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation.
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