Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other ...hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD) induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and NOD-like receptor family pyrin domain containing-3 (NLRP3) in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG) and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.
Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations ...of aspirin use in preventing breast cancer have yet to be established.
The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use).
We searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression.
Our study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer.
This paper developed a quantitative understanding of the effect of ore properties on granulation effectiveness for different iron ore types based on the mechanistic model proposed by J.D. Litster et ...al. The granulation effectiveness was measured by the magnitude of x0.5, which was postulated to be a function of the layer binding strength. Water was adopted as the only binder for all granulation tests. A wide range of moisture contents, up to the optimum moisture content that yielded an optimum permeability, was tested for each ore type. The typical structure of granules made from different ores was investigated to reveal the effect of mineralogical properties of ore particles on the growth of granules. The results indicate that the granulation effectiveness x0.5 varies markedly with ore type and moisture content. Feed particle size distribution and moisture for granulation are paramount factors determining the granulation effectiveness x0.5, which has a single relationship with the mass mean size of layering particles independent of ore type. The mass mean size of layering particles is dependent on the inherent size distribution of raw materials and the mass fraction of layering particles, while the latter is linear to available moisture content. The model works well for some ore types except for those with unreasonable size distributions: 1) excessive intermediate particles meanwhile lacking of fine particles; or 2) excessive ultrafine particles. An effective criteria closely related to layer binding strength, (1−ε)S/ε d , is proposed to determine the applicability of the model.
Triple-negative breast cancer (TNBC) patients with truly chemosensitive disease still represent a minority among all TNBC patients. The aim of the present study is to identify microRNAs (miRNAs) that ...correlate with TNBC chemoresistance.
In this study, we conducted miRNAs profile comparison between triple-negative breast cancer (TNBCs) and normal breast tissues by microRNA array. Quantitative real-time PCR (qRT-PCR) was utilized to confirm the specific deregulated miRNAs change trend. We used starBase 2.1 and GOrilla to predict the potential targets of the specific miRNAs. Cells viability and apoptosis assays were employed to determine the effect of alteration of the specific miRNAs in TNBC cells on the chemosensitivity.
We identified 11 specific deregulated miRNAs, including 5 up-regulated miRNAs (miR-155-5p, miR-21-3p, miR-181a-5p, miR-181b-5p, and miR-183-5p) and 6 down-regulated miRNAs (miR-10b-5p, miR-451a, miR-125b-5p, miR-31-5p, miR-195-5p and miR-130a-3p). Thereafter, this result was confirmed by qRT-PCR. We predicted the potential targets of the candidate miRNAs and found that they are involved in cancer-associated pathways. For the first time, we found that miR-130a-3p and miR-451a were down-regulated in TNBC. 9 of the 11 specific deregulated miRNAs were found to be associated with chemoresistance. In vitro assays, we found that up-regulation of either miR-130a-3p or miR-451a in MDA-MB-231 cells significantly changed the cells sensitivity to doxorubicin. The results suggest that TNBC chemotherapy might be affected by a cluster of miRNAs.
The abnormal expression miRNAs in TNBC are mainly chemoresistance related. This might be part of reason that TNBC likely to evade from chemotherapy resulting in early relapse and high risk of death. To alter their expression status might be a potential therapeutic strategy to improve the outcome of chemotherapy for TNBC patients.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Recently, the problem of traditional Chinese medicine (TCM) safety has attracted attention worldwide. To prevent the spread of counterfeit drugs, it is necessary to establish a drug ...traceability system. A traditional drug traceability system can record the whole circulation process of drugs, from planting, production, processing, and warehousing to use by hospitals and patients. Once counterfeit drugs are found, they can be traced back to the source. However, traditional drug traceability systems have some drawbacks, such as failure to prevent tampering and facilitation of sensitive disclosure. Blockchain (including Bitcoin and Ethernet Square) is an effective technology to address the problems of traditional drug traceability systems. However, some risks impact the reliability of blockchain, such as information explosion, sensitive information leakage, and poor scalability.
Objective
To avoid the risks associated with the application of blockchain, we propose a lightweight block chain framework.
Methods
In this framework, both horizontal and vertical segmentations are performed when designing the blocks, and effective strategies are provided for both segmentations. For horizontal segmentation operations, the header and body of the blockchain are separated and stored in the blockchain, and the body is stored in the InterPlanetary File System. For vertical segmentation operations, the blockchain is cut off according to time or size. For the addition of new blocks, miners only need to copy the latest part of the blockchain and append the tail and vertical segmentation of the block through the consensus mechanism.
Results
Our framework could greatly reduce the size of the blockchain and improve the verification efficiency.
Conclusions
Experimental results have shown that the efficiency improves compared with ethernet when a new block is added to the blockchain and a search is conducted.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung ...cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism
and metastasis assays
. As results, we reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the up-regulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis. The over-expression of IDO1 significantly encouraged the metastasis and invasion of lung cancer cells, and IDO1 could promote metastasis formation
. Furthermore, we further found that p53 could attenuate IDO signaling in lung cancer cell migration partly. In conclusion, these results demonstrate that the IDO signaling's impact on invasion and metastasis and the suppressive effect of p53 on IDO1 in lung cancer, present one novel therapeutic strategy for early metastatic lung cancer in clinical.
The mechanisms underlying the pathogenesis and progression of Parkinson's disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by ...microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia.
After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation.
We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation.
Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background:Mild cognitive impairment(MCI) is the early phase of Alzheimer’s disease (AD).The early intervention of MCI to decrease the rate of conversion from MCI to AD is significant. However, the ...efficacy of multiple interventions in MCI and which way should be preferred are still matters of controversy. Consequently, we aimed to compare and rank the treatment methods for mild cognitive impairment (MCI)due to Alzheimer's Disease (AD),to find an optimal intervention of MCI and a way to prevent or delay the occurrence of AD. Methods:We did pair-wise meta-analysis and network meta-analysis to integrate the treatment effectiveness through direct and indirect evidence.Four English databases and three Chinese databases were searched for international registers of published and unpublished,eligible double or single blind,randomized controlled trials up to September 31, 2019.Compared nine comparative arms:pharmacological therapy:Cholinesterase inhibitors（ChEI）,Ginkgo, Nimodipine,Chinese Medicine;non-pharmacological therapy:Acupuncture,Music therapy,Exercise,Nutrition therapy;and placebo. The primary outcome was Mini-Mental State Examination(MMSE) ,The second outcome was AD Assessment Scalecognitive subscale (ADAS-cog). Results:We deemed 29 trials eligible, including 6957 participants.The overall effects of Music therapy (MD: 1.73 ; 95% CI: 0.30, 3.12) and Acupuncture(MD: 1.17; 95% CI: -0.80, 3.12) exerted significant therapeutic effect ;the overall effect of exercise showed a preference for MCI treatment (MD:0.53 ;95%CI:-1.09,2.21). Nutrition and Ginkgo treatment had the lowest rank among all interventions (-0.73,-1.93 to 0.51;-0.42,-2.30 to1.46 ). Conclusion:Among the nine treatments, The Music therapy had the highest probability to be the first best treatment of MCI, and Acupuncture had the second highest probability. Significant:Our study provide new ways of thinking to the clinical treatments of MCI due to AD,and may help the development of MCI guideline.
Unlike previous dephosphorization studies, the present work complies with a concept to recover phosphorus within the utilization of high-phosphorus oolitic iron ores to prepare Fe
-
P alloy for ...high-phosphorus steel production. Simultaneous enrichment of iron and phosphorus can be achieved by directly alloying the high-phosphorus oolitic iron ore at high reduction temperatures (≥1623 K). Neither fluxes nor other special additives need to be used. Consequently, the phosphorus element migrates from original apatite to the slag phase with the elevating temperature from 1323 K to 1473 K, and it further moves into metallic iron and forms Fe
3
P at 1623 K. A metalized iron
-
phosphorus alloy with assaying of 96.51% iron and 2.03% phosphorus content was obtained at 1623 K for 10 min at corresponding iron and phosphorus recovery rates of 97.50% and 64.51%, respectively. This process exhibits high economic efficiency and is practicable as a stepping-stone for the efficient and direct utilization of high-phosphorus iron ore resources.
Abstract To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary ...intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1–2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer–Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO 2 ), carbon dioxide ventilation equivalent slope (VE/VCO 2 slop), and peak end-tidal carbon dioxide partial pressure (PETCO 2 ) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI ( P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO 2 , VE/VCO 2 slop, and PETCO 2 . The risk of adverse events was significantly reduced when the peakVO 2 was ≥ 20 mL/kg/min and the VE/VCO 2 slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer–Lemeshow test showed that the three models were a good fit ( P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
