Role of transcription factor complex OsbHLH156-OsIRO2 in regulating manganese, copper, and zinc transporters in rice.

Iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) are essential micronutrients that are necessary for plant growth and development, but can be toxic at supra-optimal levels. Plants have evolved a complex homeostasis network that includes uptake, transport, and storage of these metals. It was shown that the transcription factor (TF) complex OsbHLH156-OsIRO2 is activated under Fe deficient conditions and acts as a central regulator on Strategy II Fe acquisition. In this study, the role of the TF complex on Mn, Cu, and Zn uptake was evaluated. While Fe deficiency led to significant increases in shoot Mn, Cu, and Zn concentrations, the increases of these divalent metal concentrations were significantly suppressed in osbhlh156 and osiro2 mutants, suggesting that the TF complex plays roles on Mn, Cu, and Zn uptake and transport. An RNA-sequencing assay showed that the genes associated with Mn, Cu, and Zn uptake and transport were significantly suppressed in the osbhlh156 and osiro2 mutants. Transcriptional activation assays demonstrated that the TF complex could directly bind to the promoters of OsIRT1, OsYSL15, OsNRAMP6, OsHMA2, OsCOPT1/7, and OsZIP5/9/10, and activate their expression. In addition, the TF complex is required to activate the expression of nicotianamine (NA) and 2'-deoxymugineic acid (DMA) synthesis genes, which in turn facilitate the uptake and transport of Mn, Cu, and Zn. Furthermore, OsbHLH156 and OsIRO2 promote Cu accumulation to partially restore the Fe-deficiency symptoms. Taken together, OsbHLH156 and OsIRO2 TF function as core regulators not only in Fe homeostasis, but also in Mn, Cu, and Zn accumulation.

Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

One step accurate phase demodulation from a closed fringe pattern with the convolutional neural network HRUnet.

Retrieving a phase map from a single closed fringe pattern is a challenging task in optical interferometry. In this paper, a convolutional neural network (CNN), HRUnet, is proposed to demodulate phase from a closed fringe pattern. The HRUnet, derived from the Unet model, adopts a high resolution network (HRnet) module to extract high resolution feature maps of the data and employs residual blocks to erase the gradient vanishing in the network. With the trained network, the unwrapped phase map can be directly obtained by feeding a scaled fringe pattern. The high accuracy of the phase map obtained from HRUnet is demonstrated by demodulation of both simulated data and actual fringe patterns. Compared results between HRUnet and two other CNNS are also provided, and the results proved that the performance of HRUnet in accuracy is superior to the two other counterparts.

Ca2+-independent ZmCPK2 is inhibited by Ca2+-dependent ZmCPK17 during drought response in maize.

Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is mainly inhibited during short term abscisic acid (ABA) treatment, and dynamically changed in prolonged treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 could prevent the nuclear localization of ZmCPK2 through phosphorylation of ZmCPK2T60. ZmCPK2 interacts with and phosphorylates and activates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded directly by ZmCPK17 that inhibits ZmCPK2, thereby promoting plant adaptation to water deficit.

Rapid Surface Reconstruction of Pentlandite by High-Spin State Iron for Efficient Oxygen Evolution Reaction.

Triggering rapid reconstruction reactions holds the potential to approach the theoretical limits of the oxygen evolution reaction (OER), and spin state manipulation has shown great promise in this regard. In this study, the transition of Fe spin states from low to high was successfully achieved by adjusting the surface electronic structure of pentlandite. In situ characterization and kinetic simulations confirmed that the high-spin state of Fe promoted the accumulation of OH- on the surface and accelerated electron transfer, thereby enhancing the kinetics of the reconstruction reaction. Furthermore, theoretical calculations revealed that the lower d-band center of high-spin Fe optimized the adsorption of active intermediates, thereby enhancing the reconstruction kinetics. Remarkably, pentlandites with high-spin Fe exhibited ultra-low overpotential (245 mV @ 10 mA cm-2 ) and excellent stability. These findings provided new insights for the design and fabrication of highly active OER electrocatalysts.

The Arabidopsis Nodulin Homeobox Factor AtNDX Interacts with AtRING1A/B and Negatively Regulates Abscisic Acid Signaling.

The phytohormone abscisic acid (ABA) and the Polycomb group proteins have key roles in regulating plant growth and development; however, their interplay and underlying mechanisms are not fully understood. Here, we identified an Arabidopsis (Arabidopsis thaliana) nodulin homeobox (AtNDX) protein as a negative regulator in the ABA signaling pathway. AtNDX mutants are hypersensitive to ABA, as measured by inhibition of seed germination and root growth, and the expression of AtNDX is downregulated by ABA. AtNDX interacts with the Polycomb Repressive Complex1 (PRC1) core components AtRING1A and AtRING1B in vitro and in vivo, and together, they negatively regulate the expression levels of some ABA-responsive genes. We identified ABA-INSENSITIVE (ABI4) as a direct target of AtNDX. AtNDX directly binds the downstream region of ABI4 and deleting this region increases the ABA sensitivity of primary root growth. Furthermore, ABI4 mutations rescue the ABA-hypersensitive phenotypes of ndx mutants and ABI4-overexpressing plants are hypersensitive to ABA in primary root growth. Thus, our work reveals the critical functions of AtNDX and PRC1 in some ABA-mediated processes and their regulation of ABI4.

Efficient Visible-Light-Driven Tetracycline Degradation and Cr(VI) Reduction over a LaNi1-xFexO3 (0 ≤ x ≤ 1)/g-C3N4 Type-II Heterojunction Photocatalyst.

The development of efficient, stable, and visible-light-responsive photocatalysts is crucial to address the pollution of water bodies by toxic heavy metal ions and organic antibiotics. Herein, a series of LaNi1-xFexO3/g-C3N4 heterojunction photocatalysts are prepared by a simple wet chemical method. Moreover, LaNi0.8Fe0.2O3/g-C3N4 composites are characterized by various methods, including structure, morphology, optical, and electrochemical methods and tetracycline degradation and photocatalytic reduction of Cr(VI) under visible light irradiation. Then, the photocatalytic performance of as-prepared LaNi0.8Fe0.2O3/g-C3N4 composites is evaluated. Compared with pure LaNi0.8Fe0.2O3 and g-C3N4, the LaNi0.8Fe0.2O3/g-C3N4 composite photocatalysts exhibit excellent photocatalytic performance due to synergy of doping and constructing heterojunctions. The results show that the doping of Fe ions can increase the concentration of oxygen vacancies, which is ultimately beneficial to the formation of electron traps. Moreover, the type-II heterojunction formed between LaNi0.8Fe0.2O3 and g-C3N4 effectively strengthens the separation and transfer of photoinduced carriers, thereby promoting photocatalytic activity. Furthermore, the photocatalytic activity of the LaNi0.8Fe0.2O3/g-C3N4 photocatalyst remains almost unchanged after three cycles, indicating long-term stability. Ultimately, the photocatalytic mechanism of the LaNi0.8Fe0.2O3/g-C3N4 composites is proposed.

Electrodeposition of Self-Supported High-Entropy Spinel Oxides for Stable Oxygen Evolution.

Spinel oxides have attracted increasing interest due to their excellent activity in the oxygen evolution reaction (OER). However, despite the high intrinsic OER activity, their poor electrical conductivity and weak structural stability prevented their application for a long time. These shortcomings can be solved by effectively adjusting the electronic structures of spinel oxides through a high-entropy strategy. Herein, a rapid two-step method was developed to prepare self-supported high-entropy spinel-type oxides on a carbon cloth (CC) to yield (Fe0.2Co0.2Ni0.2Mn0.2Cr0.2)3O4@CC (abbreviated as FeCoNiMnCr@CC). The unique electronic structure and stable crystal configuration of the resulting FeCoNiMnCr@CC materials required only an overpotential of 287 mV for the OER at a current density of 10 mA cm-2 coupled with excellent cyclic stability. In summary, the proposed high-entropy strategy looks promising for improving the catalytic performance of spinel oxides.

Reliability and reproducibility of CBCT assessment of mandibular changes before and after treatment for Class III growing patients - an easy and quick way for evaluation.

The objective of this study was to evaluate intraobserver reliability and inter-observer reproducibility of a 3-dimensional (3D) assessment method for mandibular changes of growing patients after orthodontic treatment for Class III malocclusion.Methods Cone-beam computed tomography (CBCT) scans were performed before and after orthodontic treatment for 27 patients. During the scan, the patient was positioned such that his/her mandibular plane was parallel to floor. Three observers independently worked on the DICOM data, reconstructed the pre- and post-treatment 3D models in software, selected the stable anatomical structures (basal bone area from the lingual surface of the symphysis to the distal aspect of the first molars) to guide the automated superimposition process. Then, each observer registered 14 anatomical landmarks on the virtual models, for three times after suitable interval, to generate 3 sets of coordinates; the mean was taken as the coordinates for that particular landmark. The intraobserver reliability and inter-observer reproducibility of the method were analyzed.Results The ICCs was > 0.90 for 25 (92.6%) of the intraobserver assessments. The precision of the measurement method was < 0.3 mm in 24 (88.9%) cases. The interobserver reproducibility errors were < 0.3 mm in 21 of the 27 cases.Conclusions The intraobserver reliability and inter-observer reproducibility of 3D assessment of mandibular changes using the virtual models were excellent.

Construction and application of tuberculosis medical and nursing integration cooperation model.

OBJECTIVE: To explore the clinical effect of the tuberculosis (TB) doctor-nurse integration management model METHODS: This study is a retrospective historical cohort study. The clinical data of 180 patients with TB in our hospital from 2019 to 2020 were analyzed retrospectively. In a control group, 90 cases were treated with the traditional medical care model. An observation group of 90 cases received clinical diagnoses, treatments, and nursing under a doctor-nurse integration management model. Comparative analyses between the two groups were conducted on various aspects, including the awareness level of TB prevention and control, medication compliance and patient satisfaction. Comparisons between the two groups were evaluated using independent-sample t-tests or Chi-squared tests RESULTS: Compared with the control group, the knowledge awareness levels of TB prevention and medication compliance in the observation group were significantly higher (p < .05). The appointment waiting times and hospitalization times in the observation group were significantly lower than in the control group (p < .05). The total average satisfaction score of the patients in the observation group was significantly higher than in the control group (p < .05). Compared with the control group, the patients in the observation group were significantly more satisfied with their nursing methods, operating techniques, psychological techniques, service attitudes, and ward management (p < .05). In addition, in the observation group, medical-nursing relationships and doctor-patient communication were better than in the control group; additionally, the satisfaction of doctors with nursing work was also higher than in the control group, which was a statistically significant difference (p < .05) CONCLUSION: The implementation of an integrated medical-nursing cooperation model for TB will help increase the awareness of health knowledge in patients with TB, improve patient medication compliance and enhance patient satisfaction.

AUTOMATIC DETECTION AND GRADING OF DIABETIC MACULAR EDEMA BASED ON A DEEP NEURAL NETWORK.

PURPOSE: To solve the problem of automatic grading of macular edema in retinal images in a more stable and reliable way and reduce the workload of ophthalmologists, an automatic detection and grading method of diabetic macular edema based on a deep neural network is proposed. METHODS: The enhanced green channels of fundus images are input into the YOLO network for training and testing. Diabetic macular edema is graded according to the distance of the macula and hard exudate. We used multiscale feature fusion to form more comprehensive features on different grain images to improve the effect of hard exudate detection. We adopted K-means++ algorithm to cluster anchor box size and use loss of the original network to guide the regression of hard exudate bounding box and improve the regression accuracy of anchor boxes. We increased the diversity of samples for sample training by data augmentation, including cropping, flipping, and rotating of fundus images, so that each batch of training data can better represent the distribution of samples. RESULTS: The detection accuracy of the proposed method can reach 96% on the MESSIDOR data set. The detection rates of hard exudate with high, median, and low probability are 100%, 79.12%, and 60.40%, respectively. CONCLUSION: The proposed method exhibits a very good detection stability on healthy and diseased fundus images.

Phenolic Contents, Organic Acids, and the Antioxidant and Bio Activity of Wild Medicinal Berberis Plants- as Sustainable Sources of Functional Food.

Wild fruits have increasingly been investigated as part of recent searches for food products with a high antioxidant activity. In this study, wild edible berberis Berberis vulgaris collected from three different provinces (Jilin, Heilongjiang, and Liaoning) were investigated for their phenolic contents, organic acid contents, mineral contents, antioxidant activity as well as their antimicrobial potential against a range of common food borne pathogens. In addition, a physiochemical and mineral analysis of the fruits was also performed. The methanol extracts of berberis fruit collected from Jilin province were highly active against all the studied food borne bacterial pathogens, i.e., S. aureus and L. monocytogenes, E. coli, P. fluorescens, V. parahaemolyticus, and A. caviae while the berberis extracts from Heilongjiang and Liaoning showed activity only against Gram-negative bacteria. The phenolic content and antioxidant activity were determined by the HPLC separation method and ß-carotene bleaching methods, respectively. Four organic acids such as malic acid, citric acid, tartaric acid, and succinic acid were identified while a variety of phenolic compounds were detected among which catechin, chlorogenic acid, and gallic acid were found to be the predominant phenolic compounds in all three of berberis fruit samples. The berberis fruit from Jilin was found to be superior to the Heilongjiang and Liaoning fruit regarding desired physiochemical analysis; however, there were no significant differences in the mineral contents among the three samples. Overall, the berberis fruit from Jilin was ranked as the best in term of the nutritional, physiochemical, antimicrobial, and antioxidant properties. This study confirms the various useful characteristics and features of berberis at a molecular level that can be used as a sustainable source for their potential nutritional applications for making functional foods in different food industries.

Angiographic characteristics and long-term outcomes of single-vessel chronic total occlusion percutaneous coronary intervention in patients with and without previous myocardial infarction.

OBJECTIVE: This study evaluated the angiographic characteristics and clinical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) among patients with and without a history of myocardial infarction (MI). BACKGROUND: The pathogenesis of CTO and myocardial viability are different in cases with or without previous MI. However, the lesion characteristics and clinical outcomes are unclear for these two groups. METHODS: We reviewed consecutive patients who underwent single-vessel CTO PCI from 2010 to 2013. Patients were classified according to their history of MI. Acute procedural results were classified as optimal recanalization, suboptimal recanalization, or technical failure. The primary endpoint was the 5 year rate of cardiac death. RESULTS: We identified 2,191 eligible patients, including 859 patients (39.2%) with previous MI. The overall technical success rate was 74.4%. Relative to the non-MI group, the MI group had a larger reference vessel diameter (3.0 ± 0.5 vs. 2.9 ± 0.4 mm, p = .002), a lower proportion of Werner grade ≥ 1 collateral circulation (65.4 vs. 79.2%, p < .001), a higher proportion of optimal recanalization (63.1 vs. 58.6%, p = .006), and a higher 5-year rate of cardiac death (3.9 vs. 2.1%, p = .02). In the MI group, suboptimal recanalization was associated with a significantly higher 5-year rate of spontaneous MI, relative to optimal recanalization and technical failure (11.7 vs. 4.6 vs. 4.1%, p = .006). CONCLUSIONS: Patients with CTO and previous MI had a larger reference vessel diameter, lower level of collateral circulation, and higher proportion of optimal recanalization. However, suboptimal recanalization in these patients was associated with an increased risk of spontaneous MI.

Dietary soybean oil aggravates the adverse effects of low salinity on intestinal health in juvenile mud crab Scylla paramamosain.

Salinity is one of the important factors affecting the physiological state of crustaceans in marine environments. Lipid plays major roles in energy supply and is main sources of essential fatty acids for membrane integrity, which is critical in adaptations to changes in salinity. Here we evaluated the effects of salinity (medium, 23 ppt and low, 4 ppt) and dietary lipid source (fish oil, FO and soybean oil, SO) on intestinal health of the marine crustacean mud crab Scylla paramamosain. The results indicated that low salinity and dietary SO (LSO group) significantly affected intestinal histomorphology, with a significant decrease of intestinal fold height and width as well as down-regulation of intestinal mRNA levels of tight junction genes compared to crab reared at medium salinity and fed FO diets (MFO group). Crabs reared at low salinity and fed SO showed an increased inflammatory response in intestine, which stimulated a physiological detoxification response together with apoptosis compared to crab in the MFO group. Low salinity and SO diets also could be responsible for multiply the pathogenic bacteria of Photobacterium and inhibit the beneficial bacteria of Firmicutes and Rhodobacteraceae in intestine, and act on a crucial impact on the development of intestinal microbial barrier disorders. The results of microbial function predictive analysis also support these inferences. The findings of the present study demonstrated that soybean oil as the main dietary lipid source could exacerbate the adverse effects of low salinity on intestinal health of mud crab, and provided evidence suggesting that dietary lipid source and fatty acid composition may play vital roles in intestinal health and the process of adaptation to environmental salinity in marine crustaceans.

Mitigation of sand liquefaction under static loading condition using biogas bubbles generated by denitrifying bacteria.

Nitrogen bubbles that is generated by microbial denitrification process is a new pollution-free clean material for mitigation of sand liquefaction. The current study aims to assess sustainability as well as distribution character of biogas bubbles in sand column under the condition of hydrostatics along with its performance of mitigating sand liquefaction under static loading. A series of laboratory experiments were conducted, and test results indicate that biogas bubbles has excellent sustainability in sand pores, and after 92 weeks, an increase of saturation from 84.5 to 85.1% marking only 0.6% rise. The volume of biogas generated by bacteria increases linearly with decrease of depth. Under undrained condition, if saturation of sample decreased from 100% to around 92.4%, strain softening behavior will transfer to strain hardening, and undrained shear strength can be increased by approximately two times in both of compression and extension tests. The excess pore water pressure ratio and liquefaction potential index have significant reduction with the decrease of saturation, and the magnitude of impact on compression is comparatively bigger than the extension tests. This study validates that as a new material, biogas bubbles are very stable in soil, desaturation using nitrogen bubbles is an effective method for mitigating the liquefaction of sand under static loading conditions. Moreover, the study provides support for the desaturation mitigating static liquefaction of sand to prevent geological disasters and reveals its potential engineering practical value.

Effect of additives on melting temperature and energy consumption of municipal solid waste incineration fly ash.

This paper presents the melting temperature (MT) and energy consumption (EC) of model municipal solid waste incineration (MSWI) fly ash (FA) under the influence of calcium oxide (CaO), silicon dioxide (SiO2), aluminium oxide (Al2O3) and boron oxide (B2O3) based on thermochemistry simulations. Nine different base-to-acid ratios (B/A) of raw FA have been explored. The results show that the effects of CaO, SiO2 and Al2O3 vary for different B/A ranges. SiO2 and Al2O3 play positive roles in decreasing the MT and EC of FA4-FA9 with high B/A (B/A: 2.61, 4.48, 6.43, 6.90, 8.32, 8.82). CaO plays a positive role in decreasing the MT and EC of FA1 and FA2 with low B/A (B/A: 0.22, 0.43). In FA3 (B/A: 1.22), the MT and EC of FA cannot be reduced by adding CaO, SiO2 and Al2O3. The addition of B2O3 cannot only further reduce the MT of FA, but also reduce the EC. B2O3 and SiO2 can work together to reduce the MT and EC when B/A is high (2.61-8.82), and SiO2 and B2O3 can be introduced into the FA by adding waste glass and other boron containing waste to realize the coordinated disposal of waste.

LncRNA SNHG3 is activated by E2F1 and promotes proliferation and migration of non-small-cell lung cancer cells through activating TGF-ß pathway and IL-6/JAK2/STAT3 pathway.

Recently, long noncoding RNAs (lncRNAs) have been widely reported to play pivotal roles in the regulation of human cancers. Although the oncogenic property of lncRNA small nucleolar RNA host gene 3 (SNHG3) has been revealed in a variety of cancers, functions and regulatory mechanism of SNHG3 in non-small-cell lung cancer (NSCLC) remain to be investigated. In this study, we detected the upregulated expression of SNHG3 in NSCLC tissues as well as cells through quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Using Kaplan-Meier analysis, we determined that a high-level of SNHG3 was associated with a low overall survival rate of patients with NSCLC. Through gain and loss of function experiments, we demonstrated that SNHG3 had a significantly positive effect on NSCLC cell proliferation and migration. Mechanistic investigations revealed that SNHG3 was a predicted direct transcriptional target of E2F1. We observed that the transcriptional activation of SNHG3 could be induced by E2F1. To explore the mechanism, rescue experiments were carried out, which revealed that the cotreatment with SB-431542, JSI-124, or JSI-124 + SB-431542 rescued the effects brought by the overexpression of SNHG3 on NSCLC cell proliferation, migration, and epithelial-mesenchymal transition process. Our results suggested that E2F1 activated SNHG3 and promoted cell proliferation and migration in NSCLC via transforming growth factor-ß pathway and interleukin-6/janus-activated kinase 2/signal transducer and activator of transcription 3 pathway, which implied that SNHG3 may be a biomarker for the treatment of patients with NSCLC.

The relationship between ß1 -adrenergic and M2 -muscarinic receptor autoantibodies and hypertrophic cardiomyopathy.

NEW FINDINGS: What is the central question of this study? The concentrations of ß1 -adrenergic receptor and M2 -muscarinic receptor autoantibodies in hypertrophic cardiomyopathy (HCM) patients and the relationship between the cardiac autoantibodies and clinical manifestations of HCM have rarely been reported. What is the main finding and its importance? We found that the concentrations of the two autoantibodies in HCM patients were significantly higher than those in control subjects. Furthermore, we found that the concentrations of the two autoantibodies could reflect myocardial injury and diastolic dysfunction in HCM patients to some extent and might be involved in the occurrence of arrhythmia. These findings might be valuable in exploration of the mechanisms of occurrence and progression of HCM. ABSTRACT: Increasing attention is being given to the role of immunological mechanisms in the development of heart failure. The purpose of this study was to investigate the concentration of serum ß1 -adrenergic receptor autoantibody (ß1 -AAb) and M2 -muscarinic receptor autoantibody (M2 -AAb) in patients with hypertrophic cardiomyopathy (HCM), and the relationship between ß1 -AAb, M2 -AAb and clinical indices. One hundred and thirty-four patients with HCM were recruited consecutively into the HCM group. Forty healthy subjects were assigned as the normal controls (NCs). Serum samples were collected to measure the concentrations of ß1 -AAb and M2 -AAb by enzyme-linked immunosorbent assay. The clinical data of HCM patients were collected. The serum concentrations of ß1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. In HCM patients, those with a left atrial diameter ≥50 mm or moderate-to-severe mitral regurgitation had significantly higher concentrations of the two autoantibodies. Patients with a history of syncope had higher concentrations of ß1 -AAb. Female patients and patients with a family history of sudden cardiac death or atrial fibrillation had higher concentrations of M2 -AAb. Maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient were positively correlated with log ß1 -AAb or log M2 -AAb in HCM patients. In conclusion, the serum concentrations of ß1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. Being female, syncope, a family history of sudden death, atrial fibrillation, left atrial diameter ≥50 mm, moderate-to-severe mitral regurgitation, maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient may affect the concentrations of the two autoantibodies.

Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression.

Under steady-state conditions, bone marrow-derived immature myeloid cells (IMC) differentiate into granulocytes, macrophages and dendritic cells (DCs). This differentiation is impaired under chronic inflammatory conditions, which are typical for tumour progression, leading to the accumulation of IMCs. These cells are capable of inducing strong immunosuppressive effects through the expression of various cytokines and immune regulatory molecules, inhibition of lymphocyte homing, stimulation of other immunosuppressive cells, depletion of metabolites critical for T cell functions, expression of ectoenzymes regulating adenosine metabolism, and the production of reactive species. IMCs are therefore designated as myeloid-derived suppressor cells (MDSCs), and have been shown to accumulate in tumour-bearing mice and cancer patients. MDSCs are considered to be a strong contributor to the immunosuppressive tumour microenvironment and thus an obstacle for many cancer immunotherapies. Consequently, numerous studies are focused on the characterisation of MDSC origin and their relationship to other myeloid cell populations, their immunosuppressive capacity, and possible ways to inhibit MDSC function with different approaches being evaluated in clinical trials. This review analyses the current state of knowledge on the origin and function of MDSCs in cancer, with a special emphasis on the immunosuppressive pathways pursued by MDSCs to inhibit T cell functions, resulting in tumour progression. In addition, we describe therapeutic strategies and clinical benefits of MDSC targeting in cancer.

Interactions among myeloid regulatory cells in cancer.

Mounting evidence has accumulated on the critical role of the different myeloid cells in the regulation of the cancerous process, and in particular in the modulation of the immune reaction to cancer. Myeloid cells are a major component of host cells infiltrating tumors, interacting with each other, with tumor cells and other stromal cells, and demonstrating a prominent plasticity. We describe here various myeloid regulatory cells (MRCs) in mice and human as well as their relevant therapeutic targets. We first address the role of the monocytes and macrophages that can contribute to angiogenesis, immunosuppression and metastatic dissemination. Next, we discuss the differential role of neutrophil subsets in tumor development, enhancing the dual and sometimes contradicting role of these cells. A heterogeneous population of immature myeloid cells, MDSCs, was shown to be generated and accumulated during tumor progression as well as to be an important player in cancer-related immune suppression. Lastly, we discuss the role of myeloid DCs, which can either contribute to effective anti-tumor responses or play a more regulatory role. We believe that MRCs play a critical role in cancer-related immune regulation and suggest that future anti-cancer therapies will focus on these abundant cells.