Search

In order to control the discharge of regional total pollutants in the region and improve the ability of water environment management and decision making, a multi-objective decision-making optimization model of water pollution load allocation was constructed, which took into account economy and fairness. The model takes the maximum environmental benefit and the minimum weighted comprehensive Gini coefficient as the objective function and takes into account the uncertainty and multi-objectives of the model, which is conducive to promoting economic development and ensuring the fairness of regional water pollutant discharge. A method based on Monte Carlo simulation coupled with a genetic algorithm was designed to obtain the optimal solution set through multiple simulation optimization. This model is applied to Anhui Province to solve the allocation optimization problem of total pollutant reduction in the 13th Five-Year Energy Conservation and Emission Reduction Plan. After the optimization of water pollution load distribution, the comprehensive Gini coefficients of COD and NH3-N are reduced by different ranges. The comprehensive Gini coefficient after COD optimization decreased by 2.4–4.6%, and the comprehensive Gini coefficient after NH3-N optimization decreased by 25.1–32.5%, which verified the feasibility and rationality of the model in the optimal allocation of the total discharge of regional water pollutants. The model takes into account uncertain subjective and objective factors that have an important impact on water pollutant discharge targets and decision variables, thus optimizing the total emissions of the entire regional control unit in both space and time.

This study aimed to evaluate inter-laboratory classification concordance for copy number variants (CNVs) with a semiquantitative point-based scoring metric recommended by the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resources (ClinGen). A total of 234 CNVs distributed by the National Center of Clinical Laboratories (NCCLs), and 72 CNVs submitted by different laboratories, were distributed to nine clinical laboratories performing routine clinical CNV testing in China and independently classified across laboratories. The overall inter-laboratory complete classification concordance rate of the 234 distributed CNVs increased from 18% (41/234) to 76% (177/234) using the scoring metric compared to the laboratory's previous method. The overall inter-laboratory complete classification concordance rate of the 72 submitted CNVs was 65% (47/72) using the scoring metrics. The 82 variants that initially did not reach complete concordance classification and 1 additional CNV deletion were reviewed; 34 reached complete agreement, and the overall post-review complete concordance rate was 85% (260/306). Additionally, the overall percentage of classification discordance possibly impacting medical management [i.e., pathogenic (P) or likely pathogenic (LP) vs. variant of uncertain significance (VUS)] was 11% (35/306). The causes of initial and final discordance in the classification were identified. The ACMG-ClinGen framework has promoted consistency in interpreting the clinical significance of CNVs. Continuous training among laboratories, further criteria and additional clarification of the standards, sharing classifications and supporting evidence through public database, and ongoing work for dosage sensitive genes/regions curation will be beneficial for harmonization of CNVs classification.

Introduction and ObjectivesThe risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy.MethodsThe original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation.ResultsBoth in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the

Practical application of the partial nitritation–anaerobic ammonium oxidation (anammox) process has attracted increasing attention because of its low operational costs. However, the nitritation process, as a promising way to supply nitrite for anammox, is sensitive to the variations in substrate concentration and dissolved oxygen (DO) concentration. Therefore, a stable supply of nitrite becomes a real bottleneck in partial nitritation–anammox process, limiting their potential for application in mainstream wastewater treatment. In this study, five 18-L sequencing batch reactors were operated in parallel at room temperature (22°C ± 4°C) to explore the nitritation performance with different carrier materials, including sepiolite-nonwoven carrier (R1), zeolite-nonwoven carrier (R2), brucite-nonwoven carrier (R3), polyurethane carrier (R4), and nonwoven carrier (R5). The ammonia oxidation rate (AOR) in R1 reached the highest level of 0.174 g-N L−1 d−1 in phase II, which was 1.4-fold higher than the control reactor (R4). To guarantee a stable supply of nitrite for anammox process, the nitrite accumulation efficiency (NAE) was always higher than 77%, even though the free ammonia (FA) decreases to 0.08 mg-N/L, and the pH decreases to 6.8 ± 0.3. In phase V, the AOR in R1 reached 0.206 g-N L−1 d−1 after the DO content increase from 0.7 ± 0.3 mg/L to 1.7 ± 0.3 mg/L. The NAE in R1 was consistently higher than 68.6%, which was much higher than the other reactor systems (R2: 43.8%, R3: 46.6%, R4: 23.7%, R5: 22.7%). Analysis of 16S rRNA gene sequencing revealed that the relative abundance of Nitrobacter and Nitrospira in R1 was significantly lower than other reactors, indicating that the sepiolite carrier plays an important role in the inhibition of nitrite-oxidizing bacteria. These results indicate that the sepiolite nonwoven composite carrier can effectively improve the nitritation process, which is highly beneficial for the application of partial nitritation–anammox for mainstream wastewater treatment.

The interaction between plant, soil and microorganism plays a crucial role in sustainable development of terrestrial ecosystem function and diversity. However, little information is known about how plant growth, soil organic carbon (C) fractions and microorganism respond to exogenous C addition in soils with low organic C content. Three levels of 13C-glucose (equal to 0, 100% and 500% of initial microbial biomass C) were added to non-sterilized (corresponding to treatment abbreviation of CK, Glu-1, Glu-2, respectively) and sterilized soils (corresponding to treatment abbreviation of SS, SS+Glu-1, SS+Glu-2, respectively) planted with apple rootstock (Malus baccata (L.) Borkh.) seedings. The objectives of this study were to analyse the dynamics of soil organic C (SOC) fractions and soil bacterial community diversity with glucose levels and soil sterilization, and to explore the morphology of roots and nitrogen (N) metabolism by plant after glucose addition to sterilized/non-sterilized soils. Results showed that the contents of labile organic C fractions were significantly varied (P

This paper reports new geochronological (U–Pb) and isotope (C, O, and S) data to investigate the timing of mineralization and mode of ore genesis for the recently discovered Changtuxili Mn–Ag–Pb–Zn deposit, located on the western slopes of the southern Great Hinggan Range in NE China. The mineralization is hosted by intermediate–acidic lavas and pyroclastic rocks of the Baiyingaolao Formation. Three stages of mineralization are identified: quartz–pyrite (Stage I), galena–sphalerite–tetrahedrite–rhodochrosite (Stage II), and quartz–pyrite (Stage III). δ13C and δ18O values for carbonate from the ore vary from −8.51‰ to −4.96‰ and 3.97‰ to 15.90‰, respectively, which are indicative of a low-temperature alteration environment. δ34SV-CDT values of sulfides range from −1.77‰ to 4.16‰ and show a trend of equilibrium fractionation (δ34SPy ​> ​δ34SSp ​> ​δ34SGn). These features indicate that pyrite, sphalerite, and galena precipitated during the period of mineralization. The alteration mineral assemblage and isotope data indicate that the weakly acidic to weakly alkaline ore-forming fluid was derived largely from meteoric water and the ore-forming elements C and S originated from magma. During the mineralization, a geochemical barrier was formed by changes in the pH of the ore-forming fluid, leading to the precipitation of rhodochrosite. On the basis of the mineralization characteristics, new isotope data, and comparison with adjacent deposits, we propose that the Changtuxili Mn–Ag–Pb–Zn deposit is an intermediate-to low-sulfidation epithermal deposit whose formation was controlled by fractures and variability in the pH of the ore-forming fluid. The surrounding volcanic rocks yield zircon U–Pb ages of 160−146 ​Ma (Late Jurassic), indicating that the mineralization is younger than 146 ​Ma.

Background: Cardiac ryanodine receptor 2 (RyR2) dysfunction and elevated diastolic Ca2+ leak have been linked to arrhythmogenesis not only in inherited arrhythmia syndromes but also in acquired forms of heart disease including heart failure (HF) and atrial fibrillation (AF). Thus, stabilizing RyR2 may exert therapeutic effects in these conditions. Objective: The purpose of this study was to investigate the effects of stabilizing RyR2 with chronic dantrolene treatment on HF development and AF inducibility in a myocardial infarction (MI)–induced HF model in rats. Methods: MI was induced in adult Sprague-Dawley rats by ligation of the left anterior descending coronary artery. Two weeks after MI surgery, rats with large MI (≥40%) were randomly assigned to MI-vehicle (n = 14) or MI-dantrolene (10 mg/kg/d; n = 13) groups. Sham-surgery rats (n = 7) served as controls. Results: Compared to the MI-vehicle group, 4-week dantrolene treatment significantly improved cardiac function, with increased left ventricular (LV) fractional shortening (19.48% ± 3.61% vs 15.43% ± 2.65%; P

The electroencephalography (EEG) microstate has recently emerged as a new whole-brain mapping tool for studying the temporal dynamics of the human brain. Meanwhile, the neuromodulation effect of external stimulation on the human brain is of increasing interest to neuroscientists. Acupuncture, which originated in ancient China, is recognized as an external neuromodulation method with therapeutic effects. Effective acupuncture could elicit the deqi effect, which is a combination of multiple sensations. However, whether the EEG microstate could be used to reveal the neuromodulation effect of acupuncture with deqi remains largely unclear. In this study, multichannel EEG data were recorded from 16 healthy subjects during acupuncture manipulation, as well as during pre- and post-manipulation tactile controls and pre- and post-acupuncture rest controls. As the basic acupuncture unit for regulating the central nervous system, the Hegu acupoint was used in this study, and each subject’s acupuncture deqi behavior scores were collected. To reveal the neuroimaging evidence of acupuncture with deqi, EEG microstate analysis was conducted to obtain the microstate maps and microstate parameters for different conditions. Furthermore, Pearson’s correlation was analyzed to investigate the correlation relationship between microstate parameters and deqi behavioral scores. Results showed that: (1) compared with tactile controls, acupuncture manipulation caused significantly increased deqi behavioral scores. (2) Acupuncture manipulation significantly increased the duration, occurrence, and contribution parameters of microstate C, whereas it decreased those parameters of microstate D. (3) Microstate C’s duration parameter showed a significantly positive correlation with acupuncture deqi behavior scores. (4) Acupuncture manipulation significantly increased the transition probabilities with microstate C as node, whereas it reduced the transition probabilities with microstate D as node. (5) Microstate B→C’s transition probability also showed a significantly positive correlation with acupuncture deqi behavior scores. Taken together, the temporal dynamic feature of EEG microstate could be used as objective neuroimaging evidence to reveal the neuromodulation effect of acupuncture with deqi.

Background: The vein of Marshall (VOM) ethanol infusion improves sinus rhythm maintenance in patients with atrial fibrillation (AF). Distal collateral circulation of VOM can be a challenge to effective ethanol infusion. Objective: This study aimed to evaluate the feasibility and efficacy of ethanol infusion in VOM with distal collateral circulation. Methods: Patients with AF scheduled for catheter ablation and VOM ethanol infusion were consecutively enrolled. During the procedure, non-occluded coronary sinus angiography was first performed for VOM identification. After VOM identification, an over-the-wire angioplasty balloon was used for cannulation and occluded angiography of the VOM. Those with distal VOM collateral circulation were included in this study. A method of slower ethanol injection (2 mL over 5 min) plus additional balloon occlusion time for 3 min after each injection was used. Results: Of 162 patients scheduled for VOM ethanol infusion, apparent distal VOM collateral circulation was revealed in seven (4.3%) patients. Five patients had collateral circulation to the left atrium, one to the right superior vena cava, and one to the great cardiac vein. Two patients did not undergo further ethanol infusion because of our inadequate experience during the early stage of the project. Five patients had successful VOM ethanol infusion with manifest localized myocardium staining. Conclusions: Ethanol infusion in VOM with distal collateral circulation can be solved by slow injection of ethanol and enough balloon occlusion time between multiple injections.

BackgroundThe triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI).MethodsWe consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR).ResultsA total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan–Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56–1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L.ConclusionThe TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.

As a world intangible cultural heritage, acupuncture is considered an essential modality of complementary and alternative therapy to Western medicine. Despite acupuncture’s long history and public acceptance, how the cortical network is modulated by acupuncture remains largely unclear. Moreover, as the basic acupuncture unit for regulating the central nervous system, how the cortical network is modulated during acupuncture at the Hegu acupoint is mostly unclear. Here, multi-channel functional near-infrared spectroscopy (fNIRS) data were recorded from twenty healthy subjects for acupuncture manipulation, pre- and post-manipulation tactile controls, and pre- and post-acupuncture rest controls. Results showed that: (1) acupuncture manipulation caused significantly increased acupuncture behavioral deqi performance compared with tactile controls. (2) The bilateral prefrontal cortex (PFC) and motor cortex were significantly inhibited during acupuncture manipulation than controls, which was evidenced by the decreased power of oxygenated hemoglobin (HbO) concentration. (3) The bilateral PFC’s hemodynamic responses showed a positive correlation trend with acupuncture behavioral performance. (4) The network connections with bilateral PFC as nodes showed significantly increased functional connectivity during acupuncture manipulation compared with controls. (5) Meanwhile, the network’s efficiency was improved by acupuncture manipulation, evidenced by the increased global efficiency and decreased shortest path length. Taken together, these results reveal that a cooperative PFC-Motor functional network could be modulated by acupuncture manipulation at the Hegu acupoint. This study provides neuroimaging evidence that explains acupuncture’s neuromodulation effects on the cortical network.

BackgroundFOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis.MethodsBioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples.ResultsBioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3’s regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer.ConclusionWe systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in high-dose ionizing radiation-induced acute damage. Genistein has shown bioactivity in alleviating radiation damage and is currently synthesized by chemosynthetic methods. Due to concerns about chemical residues and high costs, the clinical application of genistein is still a major challenge. In this study, we aimed to establish an efficient method for the extraction of genistein from Fructus sophorae. The effects of extracted genistein (FSGen) on preventing intestinal injury from radiation were further investigated in this study. C57/BL mice were exposed to 7.5 Gy whole body irradiation with and without FSGen treatments. Histological analysis demonstrated significant structural and functional restitution of the intestine and bone marrow in FSGen-pretreated cohorts after irradiation. Through mRNA expression, protein expression, and small interfering RNA analyses, we demonstrated that FSGen protects IEC-6 cells against radiation damage by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA irradiation damage. Together, our data established an effective method to extract genistein from the Fructus sophorae plant with high purity, and validated the beneficial roles of the FSGen in protecting the radiation damage. These results promise the future applications of Fructus sophorae extracted genistein in the protection of radiation related damages.

Abstract Background Gene variants are dependable and sensitive biomarkers for target-specific therapies in breast cancer (BC). However, detection of mutations within tissues has many limitations. Plasma circulating free DNA (cfDNA) has been reported in many studies as an alternative tool for detection of mutations. But the diagnostic accuracy of cfDNA for most mutations in BC needs to be reviewed. This study was designed to perform comparative assessment of the diagnostic performance of cfDNA and DNA extracted from tissues for detection of single nucleotide variants (SNV) and copy number variants (CNV). Methods True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted from each selected study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Subgroup analysis and single study omitted analysis were performed to quantify and explain the study heterogeneity. Results Twenty eligible studies that involved 1055 cases were included in this meta-analysis. SNV studies in early breast cancer (EBC) subgroup are not suitable for meta-analysis owing to high heterogeneity. However, in advanced breast cancer (ABC) subgroup, the pooled sensitivity and specificity of detection of SNVs were 0.78 (0.71–0.84) and 0.92 (0.87–0.95), respectively. The summary receiver operative curve (SROC) exhibited an area under the curve (AUC) of 0.91(0.88–0.93). The pooled results of studies involving subgroups of PIK3CA, TP53, and ESR1 indicate that the diagnostic value of different genes is different, such as AUC for PIK3CA and TP53 were reported to be 0.96 (0.94–0.98) and 0.94 (0.91–0.95), respectively, and ESR1 had the lowest diagnostic value of 0.80 (0.76–0.83). Owing to the low sensitivity and AUC in the cases of CNV, there is no value for cfDNA-based detection of CNV based on insufficient amount of CNV data. Conclusion This meta-analysis suggests that the detection of gene mutations in cfDNA have adequate diagnostic accuracy and can be used as an alternative to the tumor tissue for detection of SNV but not for CNV in BC yet.

Based on the wave theory, different bedding structure models for shales in Lower Silurian Longmaxi Formation of southeastern Chongqing area were established, numerical simulations of responses of different bedding structures of shale to ultrasonic wave were carried out by using the second order in time and fourth order in space grid finite difference method, based on the grey system theory, sensitive factors of acoustic parameters of bedding structure were selected, and the dynamic mechanical parameter model of bedded shale was established, which was verified by the ultrasonic transmission experiment results on core down Well ZY1 and YY1 and the logging data of Well ZY2. The results show that: (1) The correlation coefficient between analog and experimental waveforms is greater than 80%, indicating that the numerical simulation method can effectively simulate ultrasonic transmission experiment. (2) Acoustic velocity is a conventional sensitive factor used to characterize shale bedding structure, whereas the attenuation coefficient is sensitive to the change of bedding thickness, with correlation coefficient of 0.89, therefore, using the normalized results of attenuation coefficient to comprehensively describe the shale bedding can make the results more accurate. (3) The correlation between the dynamic and static parameters calculated by the model is better than that of the traditional model; and the predicted values of rock mechanics obtained by using the model and logging data inversion are in good agreement with the experimental values. The research results lay the foundation for further accurate prediction of rock mechanic parameters using sonic logging data. Key words: Southeastern Chongqing, Silurian Longmaxi Formation, shale, bedding, ultrasonic transmission, numerical simulation, rock mechanics

The mechano-properties of the Extracellular Matrix (ECM) are important for tumorigenesis. Here, the authors show that the stiffening of the ECM promotes translocation of the focal adhesion protein—Kindlin-2—to the mitochondria, where it interacts with the proline synthesis enzyme PYCR1, stimulating proline synthesis and cell proliferation.

Abstract Background Subclinical hypothyroidism is a common condition in patients with heart failure and is defined as elevated serum thyroid hormone (TSH) with normal circulating free thyroxine (FT4). Evidence on the effect of thyroid hormone treatment is lacking. We designed a randomized controlled trial to compare the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. Methods/design Eligible participants were identified from the cardiology units of five study centers based on the following criteria: 18 years or older, systolic heart failure with NewYork Heart Association (NYHA) class II–III, left ventricular ejection fraction ≤ 40%, and subclinical hypothyroidism (TSH > 4.78μIU/ml,

“Satellite cells are crucial for skeletal muscle regeneration. Here the authors show that immunoglobulin superfamily containing leucine-rich repeat (Islr) promotes skeletal muscle regeneration via a mechanism involving Dishevelled-2 stabilization in satellite cells and protection from autophagy.

BackgroundThis study aims to investigate the role of free triiodothyronine (fT3) in predicting poor prognosis of adult patients with acute myocarditis.MethodsA total of 173 consecutive adult patients with acute myocarditis completed thyroid function evaluations. They were divided into two groups according to fT3 levels: low fT3 group (n = 54, fT3 < 3.54 pmol/liter) and normal fT3 group (n = 119, fT3 ≥ 3.54 pmol/liter). The primary endpoint was major adverse cardiac events (MACE).ResultsDuring the 3.5 ± 2.8 years follow-up, the rate of MACE was 29.6% versus 3.5% in low fT3 group versus normal fT3 group, respectively (P < 0.0001). Long-term at 8 years MACE-free survival were lower in low fT3 group versus normal fT3 group (52.9% versus 92.3%, log-rank P < 0.0001), respectively. Univariate Cox analysis showed that left ventricular ejection fraction (LVEF) < 50% [hazard ratio (HR) 10.231, 95% confidence interval (CI): 3.418–30.624, P < 0.0001) and low fT3 level (HR 0.360, 95% CI: 0.223–0.582, P < 0.0001) were strongest two predictors of MACE. After adjustment for traditional risk predictors, the prognostic value of fT3 status was still significant (HR 0.540, 95% CI: 0.316–0.922, P = 0.024). Compared with normal fT3 group, those in low fT3 group were at a much higher risk of MACE (HR 5.074, 95% CI: 1.518–16.964, P = 0.008).ConclusionsLow T3 syndrome was a strong predictor of poor prognosis in adult patients with acute myocarditis. These findings suggest that fT3 level could serve as a biomarker for risk stratification in acute myocarditis patients.

BackgroundHigh lipoprotein(a) (Lp[a]) levels are associated with increased risks of cardiovascular events in Percutaneous Coronary Intervention (PCI) patients with diabetes mellitus (DM). Peri-procedural myocardial infarction (PMI) occurs commonly during the PCI, whereas the relationship between Lp(a) and PMI remains unclear. Our study aimed to evaluate the association between Lp(a) value and the incidence of PMI in a larger-scale diabetic cohort undergoing PCI throughout 2013.MethodsA total of 2,190 consecutive patients with DM were divided into two groups according to the median Lp(a) level of 175 mg/L: Low Lp(a) group (N = 1095) and high Lp(a) group (N = 1095). PMI was defined based on the 2018 universal definition of myocardial infarction.ResultsPatients with high Lp(a) levels exhibited higher rates of PMI compared to those with low Lp(a) levels (2.3% versus 0.8%, P = 0.006). The multivariable logistic analysis showed that PMI was independently predicted by Lp(a) as a dichotomous variable (OR 2.64, 95%CI 1.22–5.70) and as a continuous variable (OR 1.57, 95% CI 1.12–2.20). However, further investigation found that this association was only maintained in men, whose Lp(a) levels were significantly associated with the frequency of PMI, both as a dichotomous variable (OR 3.66, 95%CI 1.34–10.01) and as a continuous variable (OR 1.81, 95%CI 1.18–2.78). Lp(a) wasn’t a risk factor of PMI in women.ConclusionsHigh Lp(a) levels had forceful correlations with the increased frequency of PMI in male diabetic patients undergoing PCI. Lp(a) might act as a marker of risk stratification and a therapeutic target to reduce PCI-related ischemic events.

To improve the traffic capacity and reduce the delay of signalized intersections, the delay of coordinated control intersections is studied. Based on the freedom and randomness of the speed change and considering the delay problem caused by the discrete behavior, the authors deduced a new delay model. Firstly, by analyzing the kinematic behavior of traffic flow under coordinated control, it is found that traffic flow reaches the downstream intersection in two different forms. The two forms were as follows: the tail vehicles of discrete traffic flow were truncated and the front vehicles of discrete traffic flow were stopped. Then, the authors deduced the new delay model by analyzing the two conditions. Finally, the delay of the two cases is analyzed, which can be used as the basis for setting the phase difference between coordinated control intersections. The correctness of the model is verified by designing two example coordinated control intersections under unsaturated flow with MATLAB. Results show that the discrete traffic flows will have different impacts on delay or traffic efficiency when they arrive at the downstream intersection in different forms. Through the analysis of the delay of vehicles, when the green split is less than 0.64, the tail truncation delay is greater than the front truncation delay. When the green split is greater than or equal to 0.64, the opposite is true. The phase difference of upstream and downstream intersections can be optimized and coordinated according to the goal that vehicles can smoothly pass through the coordinated control intersection or ensure the minimum delay, so as to give full play to the space-time utilization of the coordinated control intersection.

Exome sequencing has become an effective diagnostic method for Mendelian disorders. But the quality of services differs widely across laboratories in China, particularly in variant classification, even with the adoption of the ACMG guidelines. As an effort of quality control and improvement for better clinical utilization of exome sequencing, we assessed the exome data analysis and clinical reporting among Chinese laboratories. Five raw datasets of real clinical samples with associated phenotypes were sent to 53 laboratories. The participants independently performed secondary analysis, variant classification, and reporting. The first round of results was used for identifying problems associated with these aspects. Subsequently, we implemented several corrective actions and a training program was designed based on the identified issues. A second round of five datasets were sent to the same participants. We compared the performances in variant interpretation and reporting. A total of 85.7% (42/49) of participants correctly identified all the variants related with phenotype. Many lines of evidence using the ACMG guidelines were incorrectly utilized, which resulted in a large inter-laboratory discrepancy. After training, the evidence usage problems significantly improved, leading to a more consistent outcome. Participants improved their exome data analysis and clinical reporting capability. Targeted training and a deeper understanding of the ACMG guidelines helped to improve the clinical exome sequencing service in terms of consistency and accuracy in variant classification in China.

Abstract Tamoxifen remains the most effective treatment for estrogen receptor α (ERα)‐positive breast cancer. However, many patients still develop resistance to tamoxifen in association with metastatic recurrence, which presents a tremendous clinical challenge. To better understand tamoxifen resistance from the perspective of the tumor microenvironment, the whole microenvironment landscape is charted by single‐cell RNA sequencing and a new cancer‐associated fibroblast (CAF) subset, CD63+ CAFs, is identified that promotes tamoxifen resistance in breast cancer. Furthermore, it is discovered that CD63+ CAFs secrete exosomes rich in miR‐22, which can bind its targets, ERα and PTEN, to confer tamoxifen resistance on breast cancer cells. Additionally, it is found that the packaging of miR‐22 into CD63+ CAF‐derived exosomes is mediated by SFRS1. Furthermore, CD63 induces STAT3 activation to maintain the phenotype and function of CD63+ CAFs. Most importantly, the pharmacological blockade of CD63+ CAFs with a CD63‐neutralizing antibody or cRGD‐miR‐22‐sponge nanoparticles enhances the therapeutic effect of tamoxifen in breast cancer. In summary, the study reveals a novel subset of CD63+ CAFs that induces tamoxifen resistance in breast cancer via exosomal miR‐22, suggesting that CD63+ CAFs may be a novel therapeutic target to enhance tamoxifen sensitivity.

As international students seek degrees in U.S. institutions of higher education, their role as students is forefronted and recognizable by faculty and peers. However, what often remains invisible are international students' social and personal experiences during academic study abroad. Although there is a great deal of feminist research on academic identity and motherhood, almost nothing has been written regarding the experiences of international women who become mothers while pursuing graduate studies in the U.S. This poetic ethnographic study focuses on the lived experiences of eleven international graduate student first-time mothers from Chinese mainland and Taiwan who became new mothers during their programs of study in the U.S., especially how they kept learning their ongoing, dynamic, multifaceted, and embodied “language” of motherhood through various kinds of social interactions, and among divergent practices, beliefs, and cultures. This article explores how poetic inquiry can contribute to the understanding of international graduate student mothers’ experiences as a social, cultural, and educational phenomenon. This article also discusses the issues of ethics and self-reflexivity of conducting poetic inquiry research.

BackgroundCardiac re-expression of fetal genes in patients with heart failure (HF) suggests the presence of low cardiac tissue thyroid hormone (TH) function. However, serum concentrations of T3 and T4 are often normal or subclinically low, necessitating an alternative serum biomarker for low cardiac TH function to guide treatment of these patients. The clinical literature suggests that serum Brain Natriuretic Peptide (BNP) levels are inversely associated with serum triiodo-L-thyronine (T3) levels. The objective of this study was to investigate BNP as a potential serum biomarker for TH function in the heart.MethodsTwo animal models of thyroid hormone deficiency: (1) 8-weeks of propyl thiouracil-induced hypothyroidism (Hypo) in adult female rats were subsequently treated with oral T3 (10 μg/kg/d) for 3, 6, or 14 days; (2) HF induced by coronary artery ligation (myocardial infarction, MI) in adult female rats was treated daily with low dose oral T3 (5 μg/kg/d) for 8 or 16 wks.ResultsSix days of T3 treatment of Hypo rats normalized most cardiac functional parameters. Serum levels of BNP increased 5-fold in Hypo rats, while T3 treatment normalized BNP by day 14, showing a significant inverse relationship between serum BNP and free or total T3 concentrations. Myocardial BNP mRNA was increased 2.5-fold in Hypo rats and its expression was decreased to normal values by 14 days of T3 treatment. Measurements of hemodynamic function showed significant dysfunction in MI rats after 16 weeks, with serum BNP increased by 4.5-fold and serum free and total T3 decreased significantly. Treatment with T3 decreased serum BNP while increasing total T3 indicating an inverse correlation between these two biologic factors (r2 = 0.676, p < 0.001). Myocardial BNP mRNA was increased 5-fold in MI rats which was significantly decreased by T3 over 8 to 16 week treatment periods.ConclusionsResults from the two models of TH dysfunction confirmed an inverse relationship between tissue and serum T3 and BNP, such that the reduction in serum BNP could potentially be utilized to monitor efficacy and dosing of T3 treatment. Thus, serum BNP may serve as a reliable biomarker for cardiac TH function.

Aiming at the problem of fast certification for a constrained iris in the same category caused by the unstable iris features caused by the change of the iris acquisition environment and shooting status under lightweight training samples, a one-to-one fast certification algorithm for constrained unsteady-state iris based on the scale change stable feature and multi-algorithm voting is proposed. Scale change stable features are found by constructing an isometric differential Gaussian space, and a local binary pattern algorithm with extended statistics (ES-LBP), the Haar wavelet with over threshold detection and the Gabor filter algorithm with immune particle swarm optimization (IPSO) are used to represent the stable features as binary feature codes. Iris certification is performed by the Hamming distance. According to the certification results of three algorithms, the final result is obtained by multi-algorithm voting. Experiments with the JLU and CASIA iris libraries under the iris prerequisite conditions show that the correct recognition rate of this algorithm can reach a high level of 98% or more, indicating that this algorithm can improve the operation speed, accuracy and robustness of certification.

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

Background/Aims: The induction of excessive autophagy by increased levels of oxidative stress is one of the main mechanisms underlying unilateral ureteral obstruction (UUO)-induced vascular endothelial cell dysfunction. Hydrogen sulfide (H2S) has been shown to have an anti-oxidative effect, but its mode of action on excessive autophagy in vascular endothelial cells is unclear. Methods: Surgery was used to induce UUO in male C57BL/6 mice as an in vivo model. Human renal epithelial cells (HK-2) were treated with H2O2 as an in vitro model. NaHS was used as an exogenous H2S donor. Transmission electron microscopy was applied to observe the structure of renal autophagosomes. The expression of proteins related to autophagy and apoptosis was detected by western blot analysis in vivo and in vitro. Flow cytometry (DCFH-DA) was used to examine the levels of intracellular reactive oxygen species (ROS). The terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect cell apoptosis. Compound C was used to analyze the association of AMPK with autophagy. Results: Compared with the sham group, in which the ureter was exposed but not ligated, the cell apoptosis index, number of autophagosomes, protein expression of microtubule-associated protein 1 light-chain 3 (LC3)-II/I, beclin-1, and p-AMPK/AMPK were significantly increased in the UUO group. On the other hand, p62, cystathionine β-synthase, and cystathionine γ-lyase protein expression levels and H2S concentration were significantly decreased (p < 0.05). These alterations were ameliorated by the addition of NaHS (p < 0.05). Similar results were observed in vitro. By using the AMPK inhibitor compound C, it was indicated that AMPK was involved in ROS-induced autophagy. In addition, using tissue from patients with obstructive nephropathy, excessive autophagy was observed by an increased LC3-II/LC3-I ratio. Conclusion: NaHS-treatment may exert a protective effect on mouse kidney against UUO by suppressing the ROS-AMPK pathway. ROS-AMPK-mediated autophagy may represent a promising therapeutic target for obstructive nephropathy.

Summary: Hair follicle stem cells (HFSCs) and subsequent generations of matrix progeny make lineage choices by responding to spatiotemporal signals; however, the cues driving that specification are not well understood. Here, we demonstrate that the dynamics of microRNA (miR)-29 expression are inversely proportional to HFSC lineage progression. Furthermore, we show that sustained miR-29a/b1 overexpression in anagen or telogen in mice causes a short-hair phenotype and eventual hair loss by inhibiting the proliferation of HFSCs and matrix cells and likely preventing their differentiation. Conversely, in a loss-of-function in vivo model, miR-29a/b1 deficiency accelerates HFSC lineage progression in telogen. Mechanistically, miR-29a/b1 blocks HFSC lineage specification by spatiotemporally targeting Ctnnb1, Lrp6, Bmpr1a, and Ccna2. We further show that skin-specific Lrp6 or Bmpr1a ablation partially accounts for the short-hair phenotype. Overall, these synergistic targets reveal miR-29a/b1 as a high-fidelity antagonist of HFSC lineage progression and a potential therapeutic target for hair loss. : By using miR-29a/b1 gain- and loss-of-function mouse models, Ge et al. reveal that miR-29a/b1 suppresses lineage progression of hair follicle stem cells and matrix cells by spatiotemporally synergistic targets, Lrp6, Ctnnb1, and Bmpr1a. Keywords: miR-29a/b1, HFSC lineage progression, matrix, proliferation and differentiation, short hair, spatiotemporal targets, Lrp6, Bmpr1a, WNT pathway, BMP pathway

Abstract Background Nonalcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of excessive alcohol abuse. However, the problem that whether NAFLD is correlated with subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) remains a source of controversy. This can be attributed to the differences in diagnosis methods, population ethnicity, sampling size and bias. This study aimed to further investigate the association of NAFLD with subclinical atherosclerosis. Methods A cross-sectional study was carried out in the current study on population aged over 40 years derived from Kailuan community-based prospective study among Chinese adults from June 2010 to June 2011. NAFLD was evaluated through ultrasonography and histories of alcohol consumption. Clinical parameters and medical histories of patients were collected in the manner of interview performed by trained investigators using the standardized questionnaires. The biochemical parameters were analyzed at the central laboratory. CIMT and ba-PWV of each patient were measured. Multivariate logistic regression was used to analyze the associations of NAFLD with subclinical atherosclerosis assessed by CIMT or ba-PWV. Results A total of 4112 participants aged over 40 years were enrolled from Kailuan cohort, including 2229 men and 1883 women. The overall prevalence of NAFLD was 38.2% in the total population. Statistically significant differences were found in CIMT (P

Cerebral amyloid β-peptide accumulation is a causative factor in Alzheimer’s Disease. Here the authors design a 'nanosweeper' that binds amyloid β-peptide and induces autophagy to clear the accumulated plagues.

The components in reactor are usually exposed to cyclic loading caused by frequent startups, shutdown and load fluctuations which lead to ratcheting effect. Eurofer97 is a structural material candidate for in-vessel components of future fusion reactor. To investigate the ratcheting behavior of Eurofer97, uniaxial stress-controlled cyclic loading tests are performed at 550 °C. Ratcheting rates under various loading conditions, including various peak stresses, stress ratios and stress rates are determined to build the database of Eurofer97 for future application in the blankets of fusion reactor. An already developed unified visco-plastic constitutive model for mod.9Cr-1Mo FM steels is further applied to adapt the ratcheting behavior of Eurofer97. The developed model describes both cyclic softening in strain-controlled LCF tests and its impact on the ratcheting behavior of mod.9Cr-1Mo FM steel fairly good, at both room temperature and 550 °C. Verifying whether the current model can also describe the ratcheting behavior of Eurofer97 is a further aim of the work reported here. Keywords: Eurofer97, Ratcheting behavior, Constitutive model, 550 °C

Robustness, an ability of biological networks to uphold their functionalities in the face of perturbations, is a key characteristic of all living systems. Acupuncture is a procedure in which fine needles are inserted into an individual at discrete points and then manipulated, with the intent of preventing and curing diseases. Acupuncture does not directly eliminate pathogenic factors or pathological tissue; rather, acupuncture enhances the ability of the human body to self-medicate itself by activating complex regulatory systems and by maintaining physiological homeostasis to prevent or treat diseases. From this point of view, the effect of acupuncture on the human body is more likely a kind of regulation to promote robustness. That is to say, acupuncture has the ability to promote robustness. In this article, we review the properties and functions of acupuncture in preventing and treating diseases and in maintaining health by enhancing robustness.

In cloud-radio access network, baseband-unit (BBU) aggregation schemes have been intensively discussed to improve the efficiency of resources in light traffic times. Also, driven by the emerging optical fronthaul, traffic migration is introduced in optical fronthaul to help realize BBU aggregation, based on which traffic exchange within BBU pool can be reduced, thus decreasing corresponding processing latency and energy consumption. However, these traffic migration schemes are operated in a time-division multiplexing way and are not suitable for multi-IF over wavelength-division multiplexing (WDM) fronthaul. In this paper, we propose a reconfigurable multi-IF over WDM fronthaul to support BBU aggregation. Based on IF traffic migration and optical path reconfiguration, traffic of multiple cell sites can be routed to one BBU to achieve BBU aggregation. Proof-of-concept experiments are demonstrated to verify the feasibility of the proposed architecture. For 4G+ deployment as specified in 3GPP protocol, 100-MHz orthogonal frequency-division multiplexing signal with 64 quadratic-amplitude modulation format after transmission shows that 3.5% error vector magnitude can be achieved.

Abstract Diffusion is an important mass transfer mode of tight sandstone gas. Since nano-pores are extensively developed in the interior of tight sandstone, a considerable body of research indicates that the type of diffusion is mainly molecular diffusion based on Fick’s law. However, accurate modeling and understanding the physics of gas transport phenomena in nano-porous media is still a challenge for researchers and traditional investigation (analytical and experimental methods) have many limitations in studying the generic behavior. In this paper, we used Nano-CT to observe the pore structures of samples of the tight sandstone of western of Sichuan. Combined with advanced image processing technology, three-dimensional distributions of the nanometer-sized pores were reconstructed and a tight sandstone digital core model was built, as well the pore structure parameters were analyzed quantitatively. Based on the digital core model, the diffusion process of methane molecules from a higher concentration area to a lower concentration area was simulated by a finite volume method. Finally, the reservoir’s concentration evolution was visualized and the intrinsic molecular diffusivity tensor which reflects the diffusion capabilities of this rock was calculated. Through comparisons, we found that our calculated result was in good agreement with other empirical results. This study provides a new research method for tight sandstone digital rock physics. It is a foundation for future tight sandstone gas percolation theory and numerical simulation research.

Abstract This study compared the long term outcomes in patients with unprotected left main coronary artery (LMCA) disease who underwent stenting under the guidance of intravascular ultrasound (IVUS) or conventional angiography at a large single center. The primary outcome was the composite of all-cause death and myocardial infarction (MI) at 3 years. Target vessel revascularization (TVR) at 3 years was one of the secondary outcomes. Between January 2004 and December 2011, a total of 1,899 patients who underwent IVUS-guided (n = 713, 37.5%) or conventional angiography-guided (n = 1186, 62.5%) stenting were included. At 3 years, the unadjusted primary outcome trended lower in the IVUS-guided group versus the angiography-guided (6.9% vs. 8.4%, p = 0.22) although the TVR was similar between two groups (6.0% vs. 6.0%, p = 0.97). However, after adjustment for differences in baseline risk factors, IVUS-guidance was associated with significantly lower incidence of the composite of all-cause death and MI (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.50 to 0.84; p = 0.001), although there was still no significant difference in TVR between the two groups (HR: 1.09; 95% CI: 0.84 to 1.42; p = 0.53). IVUS guidance has benefits in improving the long-term prognosis for unprotected LMCA stenting.

Background/Aims: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

Abstract Background The early detection of type 1 diabetes (T1D) largely depends on a reliable approach to monitor β cell loss. An effective way to evaluate the decline of β cell mass would allow early preventative intervention to preserve insulin secretion. Main body Recent progress in the development of novel biomarkers, based on tissue-specific methylation patterns, has inspired relevant studies in T1D. In this review, we focus on the application of circulating β cell-derived unmethylated insulin (INS) DNA. Circulating β cell-derived unmethylated INS DNA has a potential clinical value for the early detection of T1D, surveillance of islet transplantation rejection, and evaluation of response to therapy. Utilizing differentiated methylation patterns in different organs and employing a wide variety of molecular technologies also provide insights into the interrogation of biomarkers in other diseases with massive tissue-specific cell loss. Conclusion Circulating unmethylated INS DNA is a promising molecular biomarker for the early detection of T1D.

Clustering is an important problem, which has been applied in many research areas. However, there is a large variety of clustering algorithms and each could produce quite different results depending on the choice of algorithm and input parameters, so how to evaluate clustering quality and find out the optimal clustering algorithm is important. Various clustering validity indices are proposed under this background. Traditional clustering validity indices can be divided into two categories: internal and external. The former is mostly based on compactness and separation of data points, which is measured by the distance between clusters' centroids, ignoring the shape and density of clusters. The latter needs external information, which is unavailable in most cases. In this paper, we propose a new clustering validity index for both fuzzy and hard clustering algorithms. Our new index uses pairwise pattern information from a certain number of interrelated clustering results, which focus more on logical reasoning than geometrical features. The proposed index overcomes some shortcomings of traditional indices. Experiments show that the proposed index performs better compared with traditional indices on the artificial and real datasets. Furthermore, we applied the proposed method to solve two existing problems in telecommunication fields. One is to cluster serving GPRS support nodes in the city Chongqing based on service characteristics, the other is to analyze users' preference.

Baicalin, the main active flavonoid constituent of Scutellaria baicalensis Georgi, has been reported to exert antidepressant effects. Hypothalamic-pituitary-adrenal (HPA) axis plays important roles in depression. However, antidepressant effect and mechanism of baicalin on HPA axis in hypothalamus are still unknown. In present study, we find baicalin significantly attenuates the increase of immobility time in tail suspension and forced swimming, improves the decrease of spending time in open arms, and restores the aberrant negative feedback of HPA axis in chronic corticosterone (CORT)-induced depressed mice. Moreover, proteomics finds 370 differentially expressed proteins after baicalin treatment, including 114 up-regulation and 256 down-regulation in hypothalamus. Systems biology analysis indicates the functions of differentially expressed proteins focus on phosphoserine binding and phosphorylation, especially participate in GR signaling pathway. Finally, our findings demonstrate that baicalin normalizes hypothalamic GR nuclear translocation via reducing GR phosphorylation to remodel negative feedback of HPA axis in CORT-induced mice.

Inhibition of Return (IOR) refers to an individual’s slowed localization or discrimination performance for targets that appear in previously cued versus uncued location after a relatively long delay after cue (∼300–500 ms). The current study adopted a cue-target paradigm and used behavioral and event-related potential (ERP) measures to investigate whether IOR would be modulated by emotional faces during an emotion recognition task. For reaction time measure, we found IOR effect and the magnitude of IOR effect were comparable for fearful face target and neutral face target. For ERP measures, valid cues were associated with smaller P1 and larger N1 waveform than that for invalid cues. Fearful faces were associated with a larger N170 than neutral faces. The onset latency of the stimulus-locked lateralised readiness potential (LRP) in the valid cue condition was longer than that in the invalid cue condition, while there was no significant difference on the onset latency of the response-locked LRP between the valid cue and invalid cue condition. These results support the notion that, regardless the emotion component of the stimulus, the inhibitory bias of attention to previous visited location before response contributes to the IOR.

More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV.

A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

The aim of this study was to evaluate the relationship between T helper type 17 (Th17) cells and Kawasaki disease (KD). Flow cytometry results showed that the number of Th17 cells in the peripheral blood mononuclear cells (PBMCs) of KD patients was significantly elevated. Enzyme-linked immunosorbent assay (ELISA) results showed that the serum concentrations of two Th17 cytokines, interleukin (IL)-17 and IL-6, were significantly increased in KD patients. In addition, real-time quantitative polymerase chain reaction (PCR) results showed that the messenger RNA (mRNA) expression of two molecules related to Th17 cell differentiation, retinoic acid–related orphan receptor C (RORC) and NR4A2, was upregulated in the CD4+ T cells of KD patients. Intravenous immunoglobulin (IVIG) infusion significantly reduced the proportion of Th17 cells, decreased serum concentrations of IL-7 and IL-6, and lowered the mRNA levels of RORC and NR4A2 in IVIG treatment–sensitive KD patients. Finally, the results of a Pearson’s correlation analysis illustrated that IL-17 mRNA levels in CD4+ T cells of KD patients were positively correlated with NR4A2 but not RORC mRNA expression. Our results demonstrate that Th17 cells play an important role in KD development and IVIG treatment and that Th17 cells and IL-17 may be used as markers for the occurrence of KD or as treatment targets for KD therapies. In addition, our results suggest that the underlying mechanism of IL-17 production in KD is NR4A2 dependent.

Previously, we developed a novel microRNA (miRNA) delivery system based on bacteriophage MS2 virus-like particles (MS2 VLPs). In this current study, we used this system to transport miR-146a into human peripheral blood mononuclear cells (PBMCs), and demonstrated the inhibition of osteoclastogenesis in precursors. Two cytokines, receptor activator of NF-κB ligand (RANKL), and macrophage-colony stimulating factor (M-CSF) were used to induce osteoclastogenesis. MS2 VLPs were transfected into PBMCs. qRT-PCR was applied to measure expression levels of miR-146a and osteoclast (OC)-specific genes. Western blot (WB) was conducted to evaluate miR-146a downstream target proteins: epidermal growth factor receptor (EGFR) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). The formation and activity of OCs were assessed by cytochemical staining and bone resorption assay, respectively. In PBMCs treated with MS2-miR146a VLPs, qRT-PCR assays showed increased expression of miR-146a (p < 0.01) and decreased expression of all four OC-specific genes (p < 0.05). WB results indicated decreased expression of EGFR (p < 0.01) and TRAF6 (p < 0.05). The number of OCs decreased markedly and bone resorption assay demonstrated inhibited activity. This miR-146a delivery system could be applied to induce overexpression of miR-146a and to inhibit the differentiation and function of OCs.

The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer.