Flow field around bubbles on formation of air embolism in small vessels.

An air embolism is induced by intravascular bubbles that block the blood flow in vessels, which causes a high risk of pulmonary hypertension and myocardial and cerebral infarction. However, it is still unclear how a moving bubble is stopped in the blood flow to form an air embolism in small vessels. In this work, microfluidic experiments, in vivo and in vitro, are performed in small vessels, where bubbles are seen to deform and stop gradually in the flow. A clot is always found to originate at the tail of a moving bubble, which is attributed to the special flow field around the bubble. As the clot grows, it breaks the lubrication film between the bubble and the channel wall; thus, the friction force is increased to stop the bubble. This study illustrates the stopping process of elongated bubbles in small vessels and brings insight into the formation of air embolism.

Impact of Pre-Stroke Dementia or Mild Cognitive Impairment on Stroke Outcome: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Pre-stroke dementia (PSD) and pre-stroke mild cognitive impairment (PSMCI) are important risk factors for stroke. The present meta-analysis aimed to investigate the impact of PSD or PSMCI on stroke outcomes. METHODS: Electronic databases (PubMed, EMbase, Google Scholar, Cochrane Library, and TRIP) were screened for eligible studies published prior to March 31, 2021. Risk ratios (RR) and mean differences with 95% confidence intervals (CIs) using random or fixed effect models were used to calculate pooled estimates. Study quality was assessed using the Newcastle Ottawa Scale. RESULTS: Fifteen studies were included in our meta-analysis. Pooled data from ten studies involving 3,107 PSD and 20,645 non-PSD subjects showed a higher risk of mortality in PSD patients (RR = 2.03; 95% CI: 1.40-2.91; I2 = 89%). Risk of recurrent stroke risk was observed more in patients with PSD compared to non-PSD patients (RR = 2.02; 95% CI: 1.40-2.91; I2 = 0%). Three studies involving 300 mild cognitive impairment (MCI) and 1,025 normal cognition subjects showed a significant increased risk of mortality in stroke patients with MCI (RR = 2.43; 95% CI: 1.81-3.27; I2 = 20%). However, elevated stroke severity was not observed in PSMCI patients. CONCLUSIONS: Our meta-analysis shows an increased risk of mortality in stroke patients with a history of PSD and PSMCI. Proper clinical management and increased attention are therefore required for the prevention and management of stroke in patients with cognitive deficits.

Iron and callose homeostatic regulation in rice roots under low phosphorus.

BACKGROUND: Phosphorus (Pi) deficiency induces root morphological remodeling in plants. The primary root length of rice increased under Pi deficiency stress; however, the underlying mechanism is not well understood. In this study, transcriptome analysis (RNA-seq) and Real-time quantitative PCR (qRT-PCR) techniques were combined with the determination of physiological and biochemical indexes to research the regulation mechanisms of iron (Fe) accumulation and callose deposition in rice roots, to illuminate the relationship between Fe accumulation and primary root growth under Pi deficient conditions. RESULTS: Induced expression of LPR1 genes was observed under low Pi, which also caused Fe accumulation, resulting in iron plaque formation on the root surface in rice; however, in contrast to Arabidopsis, low Pi promoted primary root lengthening in rice. This might be due to Fe accumulation and callose deposition being still appropriately regulated under low Pi. The down-regulated expression of Fe-uptake-related key genes (including IRT, NAS, NAAT, YSLs, OsNRAMP1, ZIPs, ARF, and Rabs) inhibited iron uptake pathways I, II, and III in rice roots under low Pi conditions. In contrast, due to the up-regulated expression of the VITs gene, Fe was increasingly stored in both root vacuoles and cell walls. Furthermore, due to induced expression and increased activity of ß-1-3 glucanase, callose deposition was more controlled in low Pi treated rice roots. In addition, low Pi and low Fe treatment still caused primary root lengthening. CONCLUSIONS: The obtained results indicate that Low phosphorus induces iron and callose homeostatic regulation in rice roots. Because of the Fe homeostatic regulation, Fe plays a small role in rice root morphological remodeling under low Pi.

Adiponectin Gene Polymorphism and Ischemic Stroke Subtypes in a Chinese Population.

As an adipose tissue-specific protein, adiponectin has been suggested as a protective factor for stroke, acting through anti-inflammatory and antiatherogenic effects. Therefore, we aimed to investigate whether 3 polymorphisms (rs1501299, rs2241767, and rs3774261) in the adiponectin (ADIPOQ) gene and their haplotypes were associated with ischemic stroke (IS) and its subtypes in a Chinese population. ADIPOQ gene rs1501299, rs2241767, and rs3774261 polymorphisms were analyzed in 385 IS patients, including 182 patients with large-artery atherosclerosis (LAA), 203 patients with small-vessel occlusion (SVO), and 418 matched controls. The subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism analysis. In univariate logistic analysis, the A allele frequency of rs2241767 was moderately higher in IS and LAA patients than that in controls (P = .028 and P = .017, respectively). Compared with the wide-type AA homozygote, both the genotype GG and the dominant model (GG+AG) of rs2241767 moderately increased the risk of LAA (P = .040 and P = .034, respectively). In multivariate logistic regression analysis, the genotype GG of rs2241767 was independently related to IS and LAA patients (adjusted, odds ratio [OR] = 1.822, 95% confidence interval [CI]: 1.037-3.202, P = .037 and OR = 2.051, 95% CI: 1.041-4.041, P = .038, respectively) rather than SVO. In contrast, no relationship was observed between the polymorphism of rs1501299 and rs3774261 and either subtype of IS using both univariate and multivariate logistic regression analyses. In addition, the Trs1501299-Grs2241767-Ars3774261 haplotype showed a moderately increased risk of IS and LAA (OR = 1.595, 95% CI: 1.058-2.406, P = .025 and OR = 1.709, 95% CI: 1.047-2.789, P = .031, respectively) but not of SVO. In conclusion, this study tentatively demonstrated that the polymorphism of rs2241767 and the Trs1501299-Grs2241767-Ars3774261 haplotype were associated with susceptibility to IS and LAA in a Chinese population.

Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure.

The generation of monodisperse droplets with high viscosity has always been a challenge in droplet microfluidics. Here, we demonstrate a phase-inversion co-flow device to generate uniform high-viscosity droplets in a low-viscosity fluid. The microfluidic capillary device has a common co-flow structure with its exit connecting to a wider tube. Elongated droplets of the low-viscosity fluid are first encapsulated by the high-viscosity fluid in the co-flow structure. As the elongated low-viscosity droplets flow through the exit, which is treated to be wetted by the low-viscosity fluid, phase inversion is then induced by the adhesion of the low viscosity droplets to the tip of the exit, which results in the subsequent inverse encapsulation of the high-viscosity fluid. The size of the resultant high-viscosity droplets can be adjusted by changing the flow rate ratio of the low-viscosity fluid to the high-viscosity fluid. We demonstrate several typical examples of the generation of high-viscosity droplets with a viscosity up to 11.9 Pas, such as glycerol, honey, starch, and polymer solution. The method provides a simple and straightforward approach to generate monodisperse high-viscosity droplets, which may be used in a variety of droplet-based applications, such as materials synthesis, drug delivery, cell assay, bioengineering, and food engineering.

Microfluidic Generation of High-Viscosity Droplets by Surface-Controlled Breakup of Segment Flow.

Fluids containing high concentration polymers, sols, nanoparticles, etc., usually have high viscosities, and high-viscosity fluids are difficult to be encapsulated into uniform droplets. Here we report a surface-controlled breakup method to generate droplets directly from various aqueous and nonaqueous fluids with viscosities of 1.0 to 11.9 Pa s and a dispersed-to-continuous viscosity ratio up to 1000, whereas the volume fraction of droplets up to 50% can be achieved. It provides a straightforward method to encapsulate high viscosity fluids, in a well-controlled manner in the rapid developing droplet-based applications, including materials synthesis, drug delivery, cell assay, bioengineering, etc.

The BET-Bromodomain Inhibitor JQ1 synergized ABT-263 against colorectal cancer cells through suppressing c-Myc-induced miR-1271-5p expression.

Colorectal cancer (CRC) cells undergo apoptosis in the presence of the small-molecule inhibitor ABT-263 by up-regulating antiapoptotic Bcl-2 family members. However, the resistance to ABT-263 gradually developed in most solid tumors due to its low affinity to Mcl-1. Here, we found the BET-Bromodomain inhibitor JQ1, when combined with ABT-263, synergistically reduced Mcl-1 protein level, induced apoptosis, and decreased cell viability in the CRC HCT-15, HT-29 and SW620 cells. The subsequent mechanism study revealed that a pathway of c-Myc/miR-1271-5p/Noxa/Mcl-1 underlies the synergistic effect of such combination treatment. We discovered that miR-1271-5p, the key mediator for the synergistic effect, is transcriptionally activated by c-Myc, and binds to the 3'-UTR of noxa to inhibit its protein production. The combination treatment of JQ1 and ABT-263 inhibited c-Myc protein level and also c-Myc-driven expression of miR-1271-5p, subsequently increased the protein level of Noxa, and finally promotes the degradation of Mcl-1. Our findings provide an alternative strategy to resolve the resistance during treatment of CRC by JQ1, and also discovered a novel miR-1271-5p-dependent regulatory mechanism for gene expression of noxa.

The chemokine CXCL9 expression is associated with better prognosis for colorectal carcinoma patients.

The chemokine CXCL9 has been demonstrated to play an important role in the development of human malignancies. However, its prognostic significance in cancer patients remains unclear and less is known about its role in colonrectal carcinoma (CRC) patients. In this study, we found that the relative mRNA expression level of CXCL9 in primary colorectal tumor tissues was significantly higher than that in corresponding normal colon tissues. CXCL9 protein expression was also detected in 102 of 130 primary CRC patients by immunochemistry. Thus, CXCL9 might play a vital role in the progression of colorectal cancer. By analyzing the correlation between clinicopathological factors of patients and expression of CXCL9 protein, we showed that the expression of CXCL9 was significantly associated with tumor differentiation, tumor invasion, lymph node metastasis, distant metastasis, and vascular invasion, but not with other factors of CRC patients including age, gender, tumor location and tumor size. Furthermore, by performing Kaplan-Meier method as well as Cox's univariate and multivariate hazard regression model, we found that the higher the CXCL9 expression, the higher overall survival rate was observed, and CXCL9 expression was a significant independent prognostic factor for CRC patients. Therefore, CXCL9 is a useful predictor of better clinical outcome in CRC patients.

Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers.

Local recurrence (LR) has an adverse impact on rectal cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) is increasingly administered to patients with progressive cancers to improve the prognosis. However, LR still remains a problem and its pattern can alter. Correspondingly, new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies. These risk factors are decisive when reviewing treatment options. This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance. A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT. Outcomes of interest, especially potential risk factors for LR in patients with nCRT, were then analyzed. The clinical importance of these risk factors is discussed. Remnant cancer cells, lymph-nodes and tumor response were found to be major risk factors. Remnant cancer cells decide the status of resection margins. Local excision following nCRT is promising in ypT0-1N0M0 cases. Dissection of lateral lymph nodes should be considered in advanced low-lying cancers. Although better tumor response resulted in a relatively lower recurrence rate, the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT. LR cannot be totally avoided by current multidisciplinary approaches. The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.