Search

Previous studies have suggested that microwave (MW) radiation with certain parameters can induce spatial memory deficits. However, the effect of MW on the topological organization of the brain network is still unknown. This work aimed to investigate the topological organization of the brain network in rats with spatial memory impairments induced by acute microwave (MW) radiation. The Morris water maze (MWM) test and resting-state functional magnetic resonance imaging were performed to estimate the spatial memory ability and brain network topological organization of the rats after MW exposure. Compared with the sham group, the rats exposed to 30 mW/cm2 1.5 GHz MW radiation exhibited a significantly decreased normalized clustering coefficient (γ) (p = 0.002) 1 d after the exposure and a prolonged average escape latency (AEL) (p = 0.014) 3 d after the exposure. Moreover, after 10 mW/cm2 1.5 GHz MW radiation, a significantly decreased γ (p = 0.003) was also observed in the rats, without any changes in AEL. In contrast, no adverse effects on AEL or topological parameters were observed after 9.375 GHz MW radiation. In conclusion, the rats with spatial memory deficits induced by MW radiation exhibited disruptions in the topological organization of the brain network. Moreover, these topological organization disruptions emerged earlier than behavioral symptom onset and could even be found in the rats without a decline in the performance of the spatial memory task. Therefore, it is possible to use the topological parameters of the brain network as early and sensitive indicators of the spatial memory impairments induced by acute MW radiation.

Estrus is crucial for cow fertility in modern dairy farms, but almost 50% of cows do not show the behavioral signs of estrus due to silent estrus and lack of suitable and high-accuracy methods to detect estrus. MiRNA and exosomes play essential roles in reproductive function and may be developed as novel biomarkers in estrus detection. Thus, we analyzed the miRNA expression patterns in milk exosomes during estrus and the effect of milk exosomes on hormone secretion in cultured bovine granulosa cells in vitro. We found that the number of exosomes and the exosome protein concentration in estrous cow milk were significantly lower than in non-estrous cow milk. Moreover, 133 differentially expressed exosomal miRNAs were identified in estrous cow milk vs. non-estrous cow milk. Functional enrichment analyses indicated that exosomal miRNAs were involved in reproduction and hormone-synthesis-related pathways, such as cholesterol metabolism, FoxO signaling pathway, Hippo signaling pathway, mTOR signaling pathway, steroid hormone biosynthesis, Wnt signaling pathway and GnRH signaling pathway. Consistent with the enrichment signaling pathways, exosomes derived from estrous and non-estrous cow milk both could promote the secretion of estradiol and progesterone in cultured bovine granulosa cells. Furthermore, genes related to hormonal synthesis (CYP19A1, CYP11A1, HSD3B1 and RUNX2) were up-regulated after exosome treatment, while exosomes inhibited the expression of StAR. Moreover, estrous and non-estrous cow-milk-derived exosomes both could increase the expression of bcl2 and decrease the expression of p53, and did not influence the expression of caspase-3. To our knowledge, this is the first study to investigate exosomal miRNA expression patterns during dairy cow estrus and the role of exosomes in hormone secretion by bovine granulosa cells. Our findings provide a theoretical basis for further investigating milk-derived exosomes and exosomal miRNA effects on ovary function and reproduction. Moreover, bovine milk exosomes may have effects on the ovaries of human consumers of pasteurized cow milk. These differential miRNAs might provide candidate biomarkers for the diagnosis of dairy cow estrus and will assist in developing new therapeutic targets for cow infertility.

venetoclax (VEN) and Azacitidine (AZA) combination have shown improved survival and excellent responses in patients with untreated Acute myeloid leukemia (AML). However, frequent dose reduction (or discontinuation) occurred due to therapy-related toxicity and may limit triplet combination tolerance. This study retrospectively analyzed the characteristics and outcomes of newly diagnosed AML patients who received 100mg VEN for 14 days combined with AZA at our institution. Overall, 36 patients were enrolled, the median age at diagnosis was 64 years; after a median follow-up of 15(range 4–29) months, median overall survival (OS) and progression-free survival (PFS) for the total cohort were 17 (4–29) months and 12 (1–28) months, and for patients achieving composite complete remission (CRc) were not reached. Overall response rate (ORR) was 69.4% and CRc rate were 66.7% for the total cohort. Subgroup analysis revealed that NPM1 mutations and FAB-M5 were associated higher response rates, while adverse ELN risk group predicted inferior response. ASXL1, NPM1 and IDH1/2 mutation was statistically significant impact the PFS duration. The most common adverse events were hematological, with grade 3 or 4 neutropenia, thrombocytopenia, and anemia reported in 36%, 25%, 44% of patients, respectively. In summary, the VEN combination regimen remains effective for newly diagnosed AML in the real world despite VEN dose reductions.

Background Preeclampsia is a common complication of pregnancy seriously affecting the health of mothers and babies. There is no independent methods for diagnosing and monitoring preeclampsia with sufficient accuracy, specificity and sensitivity. Changes in body metabolism usually occur before the appearance of clinical symptoms of the disease. Therefore, predicting the occurrence and development of preeclampsia by detecting changes in metabolites has become a research trend in this field. Methods In this study, a nontargeted metabolomics approach based on liquid chromatography (LC)-mass spectrometry (MS) was used to analyze the metabolites in the serum, placenta and fetal serum samples of 6 cases of late preeclampsia patients and 6 cases of normal pregnant women. Combine multivariate and univariate statistical methods to screen the endogenous differential metabolites in each sample, and use MetaboAnalyst software to perform enrichment analysis on the metabolic pathways involved in these differential metabolites. In addition, based on a binary logistic regression model to screen biomarkers that may be used to predict preeclampsia. Results Compared with normal pregnant women, there were significant differences in serum, placental and fetal serum metabolic profiles of late preeclampsia patients. We found that the late preeclampsia patients mainly had metabolic abnormalities in the metabolic pathways of ALA, taurine, glycine, serine and threonine; in addition, placenta samples showed abnormalities in the metabolic pathways of linolenic acid, taurine, α-linoleic acid and other unsaturated fatty acids, which in turn caused abnormalities in the metabolic pathways of glutamine and glutamate, ALA, alanine, aspartic acid and glutamate, and other polyunsaturated fatty acids in the fetuses of these patients. Moreover, we generated the ROC curves of differential metabolites using a binary logistic regression model and selected four serum metabolites with an AUC value greater than 0.9, most of which were polyunsaturated fatty acids. Conclusions There are significant differences in serum, placental, and fetal serum metabolic profiles between late preeclampsia patients and normal third trimester pregnant women in this study and influence the metabolic phenotypes of offspring. This result not only provides a meaningful biomarker for the diagnosis of preeclampsia, but also provides a basis for understanding the pathogenesis of preeclampsia.

Background: Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) technique could not only quantify blood-retinal barrier (BRB) breakdown leading to macular edema associated with diabetes, but also provide a two-dimensional imaging method that is not interfered by refracting media. Objective: The current study was aimed to evaluate the macular change in the patients with diabetic retinopathy using DCE-MRI technique. Methods: Twenty patients with Diabetic Retinopathy (DR) and 20 Normal Controls (NC) were included. The fast spoiled gradient echo sequence was used to perform dynamic contrast T1WI enhancement on 3.0T MR system. The macular region, optic papila and nasal retina were performed with quantitative DCE-MRI evaluation using Omni-Kinetics software. Results: The maximal concentration, the area under the concentration-time curve (AUCconcentration-time) and maximal slope of macular region were significantly higher in DR [0.270(0.03,1.20)mmol/ 100ml, 2.71(0.04,9.91) mmol*min and 0.38(0.06,3.18) mmol/min, respectively] than that [0.169(0.03,0.72) mmol/1.25(0.13,10.41) mmol*min and 0.245(0.06,1.34) mmol/min] in NC (U value = 515.00 and P value = 0.080, U value = 433.00 and P value = 0.000, and U value = 563.00 and P value = 0.023, respectively). The receiver operating characteristic curve (ROC) analysis demonstrated that the area under AUCconcentration-time was 0.729±0.058 with the cut-off value 1.479 mmol*min (sensitivity 80.00% and specificity 62.50%) for macular region. Conclusion: The quantitative DCE-MRI technique could be used to evaluate the maculopathy associated with diabetic retinopathy.

Objective Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. Methods The expression of tumour necrosis factor (TNF)-α was evaluated in normal and preeclampsia pregnant women. PYR (20 mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-α (150 ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-α-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. Results Preeclampsia women had higher placental TNF-α expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-α-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-α decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. Conclusion Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-α but also by acting against TNF-α-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.

Pyroptosis-related genes (PRGs) have been reported to be associated with prognosis of lung adenocarcinoma (LUAD). Until now, the relationship of PRGs to the prognosis of LUAD patients and its underlying mechanisms have been poorly elucidated. Using The Cancer Genome Atlas (TCGA) LUAD cohort, a prior bioinformatics analysis constructed a prognostic signature incorporating 5 PRGs (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for predicting prognosis of LUAD patients. However, it has not been validated by the Gene Expression Omnibus (GEO) LUAD cohort yet. We implemented a modified bioinformatics analysis to, respectively, construct one prognostic signature with the TCGA cohort and with the GEO cohort and attempted to perform cross-validations by the GEO cohort and the TCGA cohort alternately in turn. Univariate and multivariate Cox regression analysis screened PRGs and constructed 2 prognostic signatures with the TCGA and GEO cohorts. All LUAD samples were classified into high- and low-risk groups according to the median risk score that was generated by regression formula. Kaplan-Meier survival analysis compared the overall survival rate between the 2 risk groups, and receiver operating characteristic curve analysis evaluated predictive performance of the 2 signatures. Additionally, risk score, combined with clinicopathological features, was subjected to multivariate Cox regression analysis, to evaluate independent prognostic value of the 2 signatures. Finally, the 2 signatures received cross-validations by the GEO and TCGA cohorts, alternately. The TCGA cohort yielded a 3-gene signature (PYCARD, NLRP1, and NLRC4), whereas the GEO cohort built a 7-gene signature (SCAF11, NOD1, NLRP2, NLRP1, GPX4, CASP8, and AIM2) for predicting the prognosis of LUAD patients. Multivariate analysis proved independent prognostic value of risk score in the TCGA cohort (hazard ratio, = 1.939,; P = 8.43 × 10-4) and the GEO cohort (hazard ratio, = 2.291,; P = 4.34 × 10-9). Cross-validations confirmed prognostic value for the 7-gene signature from the GEO cohort by the TCGA cohort but not for the 3-gene signature from the TCGA cohort by the GEO cohort. We develop and validate a 7-gene prognostic signature (SCAF11, NOD1, NLRP2, NLRP1, GPX4, CASP8, and AIM2) with independent prognostic value for patients with LUAD.

In this paper, we study the fault-tolerant capability of hypercubes with respect to the hamiltonian property based on the concept of forbidden faulty sets. We show, with the assumption that each vertex is incident with at least three fault-free edges, that an [Formula: see text]-dimensional hypercube contains a fault-free hamiltonian cycle, even if there are up to [Formula: see text] edge faults. Moreover, we give an example to show that the result is optimal with respect to the number of edge faults tolerated.

The probable nanotoxicity to human health and the environment is a significant challenge for the sustainable application of nanomaterials in medicine. The cytototoxical effect of succimer (meso-2,3-dimercaptosuccinic acid-DMSA) coated titanium dioxide (DMSA-TiO2) with cultured human aortic endothelial cells (HAoECs) was assessed in this investigation. Our findings have shown that DMSA-TiO2 can be accumulated in HAoECs and dispersed in a cytoplasm on the culture medium. DMSA-cytotoxicity TiO2 effects were dose-responsive, and the concentrations were of little toxicity, and MTT stain testing showed that they had only 0.02 mg ml−1. Meanwhile, the lactate dehydrogenase biomarker was not considerably more remarkable than the biomarker from untreated (control) cells (free DMSA-TiO2). Though, also without any apparent signs of cell damage, the endocrine functions for prostacyclin I-2 and endothelin-1 and the urea transporter functions were modified. In addition, in vitro endothelial tube development has been shown that HAoECs could induce angiogenesis even with small amounts of DMSA-TiO2 (0.01 and 0.02 mg ml−1). Further, we have examined the in vivo toxicity and biochemical parameter by animal model. Furthermore, in vivo assessments designated that the resulting DMSA-TiO2 presented synergistic activities of angiogenesis activity. Overall, these findings show the cytotoxicity of DMSA-TiO2 and could induce adverse effects on normal endothelial cells.

The tree connectivity, as a generalization of the traditional connectivity, can serve to measure the capability of connection for vertices in a network. The ( n , k ) -star graph S n , k can be used to model the topological structure of a large-scale parallel processing system. We show in this article that the 4-set tree connectivity of S n , k is n − 2 , that is, there exist ( n − 2 ) internally disjoint trees connecting x , y , z and w in S n , k for four arbitrary vertices x , y , z and w of S n , k . Two known results about the 3-set tree connectivity of star graphs and ( n , k ) -star graphs are immediate consequences of our result.