Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti‐VEGF antibody is widely used in clinical practice. However, about 27% of ...patients show poor response to anti‐VEGF therapy and about 50% of these patients continue to have macular thickening. Frequent intravitreal injections of antibody may increase the chance of endophthalmitis and cause visual loss or even blindness once happened. Therefore, there is a greatly urgent need for novel noninvasive target to treat DR clinically. Here, the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing soluble semaphorin 4D (sSema4D), a strongly pro‐angiogenesis and exudates factor, is reported. The SSP nanostructures encapsulate sSema4D so that all biological effects mediated by three receptors of sSema4D are inhibited, thereby significantly alleviating pathological retinal angiogenesis and exudates in DR. Moreover, it is found that combination of SSPs eye drop and anti‐VEGF injection shows better therapeutic effect over anti‐VEGF treatment alone. Overall, SSP eye drop provide an alternative and effective method for noninvasive treatment for DR.
Diabetic retinopathy is the leading cause of vision loss in working age population. Here, the formulation of a smart supramolecular peptide (SSP) eye drop that can significantly decrease pathological retinal neovascularization and vascular leakage is reported. More importantly, it is found that combination of SSP eye drop and anti‐VEGF injection shows ≈1.5 times better therapeutic effect over anti‐VEGF treatment alone.
The prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study ...was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival.
Four hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis.
We found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61-0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28.
In conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient's risk of death.
new strategy of outlier detection for QSAR/QSPR Cao, Dong-Sheng; Liang, Yi-Zeng; Xu, Qing-Song ...
Journal of computational chemistry,
February 2010, Letnik:
31, Številka:
3
Journal Article
Recenzirano
The crucial step of building a high performance QSAR/QSPR model is the detection of outliers in the model. Detecting outliers in a multivariate point cloud is not trivial, especially when several ...outliers coexist in the model. The classical identification methods do not always identify them, because they are based on the sample mean and covariance matrix influenced by the outliers. Moreover, existing methods only lay stress on some type of outliers but not all the outliers. To avoid these problems and detect all kinds of outliers simultaneously, we provide a new strategy based on Monte-Carlo cross-validation, which was termed as the MC method. The MC method inherently provides a feasible way to detect different kinds of outliers by establishment of many cross-predictive models. With the help of the distribution of predictive residuals such obtained, it seems to be able to reduce the risk caused by the masking effect. In addition, a new display is proposed, in which the absolute values of mean value of predictive residuals are plotted versus standard deviations of predictive residuals. The plot divides the data into normal samples, y direction outliers and X direction outliers. Several examples are used to demonstrate the detection ability of MC method through the comparison of different diagnostic methods.
The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations ...is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76;
= 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99;
= 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19;
= 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12;
= 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22;
= 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56;
= 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs.
Mast cells (MCs), the 'first responders' in brain injury, are able to disrupt the blood-brain barrier (BBB), but the underlying mechanism is not well understood. Tryptase is the most abundant MC ...secretory product. Protease-activated receptor 2 (PAR-2) has been identified as a specific receptor for tryptase, which is abundantly expressed in brain microvascular endothelial cells. The BBB comprises brain microvascular endothelial cells that display specialised molecular properties essential for BBB function and integrity. Therefore, the purpose of the present study was to investigate the effects of tryptase on mouse brain microvascular endothelial cell line bEnd3 and its potential mechanisms of action.
Induction of mouse brain microvascular endothelial cell activation by tryptase was examined. Then, mouse brain microvascular endothelial cells were pretreated with a PAR-2 antagonist and stimulated with tryptase. Cellular activation, proinflammatory cytokine production, expression of PAR-2, Toll-like receptors (TLRs) and mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-kappa B) phosphorylation were assessed.
Tryptase upregulated the production of VCAM-1, MMPs (MMP9 and MMP2), TLR4 and TNF-α and downregulated the expression of the tight junction proteins occludin and claudin-5 in mouse brain microvascular endothelial cell. Among the MAPK and NF-kappa B pathway, ERK and NF-kappa B were activated by tryptase. All of these effects could be eliminated by the PAR-2 inhibitor.
Based on our findings, we conclude that tryptase can trigger brain microvascular endothelial cell activation and proinflammatory mediator release. These findings may further clarify the involvement and mechanism of tryptase in BBB disruption.
Slightly acidic electrolyzed water (SAEW), considered as a broad-spectrum and high-performance bactericide are increasingly applied in the food industry. However, its disinfection mechanism has not ...been completely elucidated. This study aims to examine the disinfection efficacy and mechanism of SAEW on Staphylococcus aureus, compared with that of sodium hypochlorite (NaClO) and hydrochloric acid (HCl). SAEW treatment significantly reduced S. aureus by 5.8 log CFU/mL in 1 min, while 3.26 and 2.73 log reductions were obtained with NaClO and HCl treatments, respectively. A series of biological changes including intracellular potassium leakage, TTC-dehydrogenase relative activity and bacterial ultrastructure destruction were studied following disinfection treatment of S. aureus. The results showed that SAEW decreased the relative activity of TTC-dehydrogenase by 65.84%. Comparing intracellular potassium leakage, the SAEW treatment caused a greater percent of protein leakage (108.34%) than the NaClO (18.75%) or HCl (0.84%) treatments. These results demonstrated the potent impact SAEW had on the permeability of cell membranes. In addition, the ranking of partly agglutinated cellular inclusion formation was HCl > SAEW > NaClO. It appeared that HCl, along with its low pH value, are responsible for most of the cytoplasmic disruptions. Overall, this study demonstrated that the disinfection mechanism of SAEW was disrupting the permeability of cell membrane and the cytoplasmic ultrastructures in S. aureus cells.
•Disinfection mechanism of slightly acidic electrolyzed water was investigated against Staphylococcus aureus.•SAEW treatment had higher disinfection efficacy compared to NaClO and HCl.•SAEW had significantly effects on the permeability of cell membranes.•The ranking of partly agglutinated cellular inclusion formation was HCl > SAEW > NaClO.
A ruthenium complex Ru(phen)
2
(phen-5-amine)-C14 (
Ru-C14
) with broad-spectrum antibacterial activity was designed and synthesized; positively charged
Ru-C14
could target bacteria
via
electrostatic ...interactions and showed high binding effectiveness to cell membranes. In addition,
Ru-C14
could act as a photosensitizer. Under 465 nm light irradiation,
Ru-C14
could generate
1
O
2
, thus disrupting the bacterial intracellular redox balance and leading to bacterial death.
Ru-C14
also exhibited minimum inhibitory concentration values of 6.25 μM against
Escherichia coli
and 3.125 μM against
Staphylococcus aureus
; these values are lower than those of streptomycin and methicillin. This work combined the merits of cell membrane targeting and photodynamic therapy for antibacterial activity. The findings might open up a new avenue for effective anti-infection treatment and other medical applications.
A ruthenium complex Ru(phen)
2
(phen-5-amine)-C14 (
Ru-C14
) with broad-spectrum antibacterial activity was synthesized.
Ru-C14
can target and image the cell membrane and can be used as a photosensitizer for photodynamic antimicrobial therapy under 465 nm light irradiation.
The collapse of abandoned room-and-pillar mines is often violent and unpredictable. Safety concerns often resulted in mine closures with no post-mining stability evaluations. As a result, large ...amounts of land resources over room-and-pillar mines are wasted. This paper attempts to establish an understanding of the long-term stability issues of goafs (abandoned mines). Considering progressive pillar failures and the effect of single pillar failure on surrounding pillars, this paper proposes a pillar peeling model to evaluate the long-term stability of coal mines and the associated criteria for evaluating the long-term stability of room-and-pillar mines. The validity of the peeling model was verified by numerical simulation, and field data from 500 pillar cases from China, South Africa, and India. It is found that the damage level of pillar peeling is affected by the peel angle and pillar height and is controlled by the pillar width–height ratio.
Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with ...AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (
P
< 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (
P
< 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.
The TGA transcription factors, a subfamily of bZIP group D, play crucial roles in various biological processes, including the regulation of growth and development as well as responses to pathogens ...and abiotic stress. In this study, 27
genes were identified in the soybean genome. The expression patterns of
genes showed that several
genes are differentially expressed under drought and salt stress conditions. Among them,
was strongly induced by both stress, which were verificated by the promoter-GUS fusion assay.
encodes a nuclear-localized protein with transcriptional activation activity. Heterologous and homologous overexpression of
enhanced tolerance to drought and salt stress in both transgeinc
plants and soybean hairy roots. However, RNAi hairy roots silenced for
exhibited an increased sensitivity to drought and salt stress. In response to drought or salt stress, transgenic
plants had an increased chlorophyll and proline contents, a higher ABA content, a decreased MDA content, a reduced water loss rate, and an altered expression of ABA- responsive marker genes compared with WT plants. In addition, transgenic
plants were more sensitive to ABA in stomatal closure. Similarly, measurement of physiological parameters showed an increase in chlorophyll and proline contents, with a decrease in MDA content in soybean seedlings with overexpression hairy roots after drought and salt stress treatments. The opposite results for each measurement were observed in RNAi lines. This study provides new insights for functional analysis of soybean TGA transcription factors in abiotic stress.
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