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Background The beneficial effects of polyphenols have been reported. This study aimed to investigate the effect of oral Ellagic acid (EA) supplement on insulin resistance (IR) and Fetuin-A and serum sirtuin1 (SIRT1) in type 2 diabetics. Methods In this double-blind, randomized clinical trial, 44 diabetic patients were selected. Patients were assigned to the intervention group (22 subjects) and placebo (22 subjects) and received a capsule containing 180 mg of EA per day or placebo for eight weeks, respectively. At the beginning and end of the study, anthropometric indices, fasting plasma glucose (FPG), plasma insulin level, IR, Fetuin-A, and SIRT1 were measured. Statistical analysis was performed using SPSS software. Results At the beginning and end of the study, there was no significant difference between the two groups regarding anthropometric indices (P > 0.05). At the end of the survey, EA supplementation significantly reduced FPG, insulin, IR, and Fetuin-A and increased SIRT1 levels compared with the placebo group (P 0.05). Conclusion EA with antioxidant properties plays an essential role in reducing the macrovascular and microvascular complications of diabetes by reducing inflammation and insulin resistance. Trial registration The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials (http://www.IRCT.IR, identifier: IRCT20141025019669N13)

Introduction: Allograft transplantation is an effective end-point therapy to replace the function of an impaired organ. The main problem associated with allotransplantation is the induction of immune responses that results in acute and chronic graft rejection. To modulate the response of the immune system, transplant recipients generally take high dose immunosuppressant drugs for life. These drugs are associated with serious side effects such as infection with opportunistic pathogens and the development of neoplasia.\ud Areas covered: We reviewed the obstacles to successful transplantation and PLGA-based strategies to reduce immune-mediated allograft rejection.\ud Expert opinion: Biomaterial-based approaches using micro- and nanoparticles such as poly (lactic-co-glycolic acid) (PLGA) can be used to achieve controlled release of drugs. This approach decreases the required effective dose of drugs and enables local delivery of these agents to specific tissues and cells, whilst decreasing systemic effects.

The hypermethylation of CpG islands in the promoter of tumor-suppressor genes (TSGs) leads to silencing the transcription of tumor suppressors, which lead to the development of cancer. The hypermethylation of CXX1 and CDH1 genes, as TSGs, plays an essential role in the development of various types of cancer, i.e., colorectal and gastric cancer. This study aims at evaluating the expression level of CXX1 and CDH1 genes and the methylation status of CXX1 CpG island's promoter in breast cancer (BC).In this study, the expression level of the CXX1 and CDH1 genes and the promoter methylation status of the CXX1 gene were evaluated in 30 paraffin-embedded tissue blocks of malignant BC and 18 benign breast lesions, using quantitative reverse transcription-PCR and methylation-specific (MS)-PCR assays, respectively.The CXX1 gene was downregulated in the malignant tissues due to the hypermethylation of the CpG islands in the promoter, compared to the control group (P = 0.031). The downregulation of CDH1 gene expression was observed in the patient group compared to control, but this reduction was not statistically significant. The results show that the risk of BC is increased with aging (P0.001). Furthermore, the benign breast lesions (controls) had more mobility in comparison with the malignant breast tumors (P0.001). In the malignant samples, the size of the mass was larger than control's mass samples (P = 0.006).In the pathophysiological state of BC, the aberrant DNA hypermethylation in CpG island of CXX1 promoter is responsible for the reduction of its expression level in BC patients.

Background: Consumption of herbal flavonoids instead of chemical drugs has increased in recent years due to fewer side effects and affordability. In this study, the effect of apigenin was investigated on inflammation induced by lipopolysaccharide in male rat's serum by measuring the pro-inflammatory cytokines, i.e., IL-1β, IL-6, and TNF-α.Methods: 90 male Wistar rats weighing 200 ±2 grams were used and divided into control, sham (solvent), and positive control (dexamethasone 15 mg/kg. ip), and 3 experimental groups which received 5, 15 or 30 mg/kg of apigenin, intraperitoneally. In 30 minutes after interventions, lipopolysaccharide (LPS) [30 μg/kg. ip] was injected. Then, at 4, 12- and 24-hour intervals, rats were anesthetized, and blood samples were prepared intracardially. Samples were centrifuged, and serums were separated and stored at -80 ° C. Measurement of IL-1β, IL-6, and TNF-α were conducted by the enzyme-linked immunosorbent assay (ELISA) method. Data were analyzed using the SPSS software version 19.Results: Pre-injection of apigenin at 5 mg/kg dosage were reduced TNF-α and IL-1β levels at 24-hours after LPS injection, compared to control (for both P P ) and 24- (P ) hours, IL-1β level at 24-hours (P ), and IL-6 level at 4- (P ) and 24- (P ) hours after LPS injection.Conclusions: Apigenin reduces proinflammatory cytokines in serum in acute inflammation induction. This impact is close to the dexamethasone effect as an anti-inflammatory steroid drug.

Background T cell immunoglobulin and mucin domain 3 (TIM-3), as a co-inhibitory receptor expressed on Th1, Th17, CD8T, FoxP3 + Treg and innate immune cells, plays an important role in suppression of T cell-mediated immune responses, tolerance induction and T cell exhaustion. In this study, we evaluated sequential alterations of TIM-3 mRNA expression level in blood and urine samples of renal transplant recipients to predict approaching clinical episodes. Methods A total of 52 adult renal transplant recipients (31 male and 21 female) were enrolled in this study. All the patients received kidney transplant from living unrelated donors. TIM-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and urinary cells were quantified using Real Time TaqMan polymerase chain reaction (PCR) at 4 different time points (pre-transplantation, 2, 90 and 180 days post-transplantation). Result TIM-3 mRNA expression level on days 2, 90 and 180 after transplantation was significantly higher in blood and urine samples of patients with graft dysfunction (GD) compared with patients with well-functioning graft (WFG). Our results also showed a high correlation between blood and urinary level of TIM-3 mRNA expression. The data from Receiver Operating Characteristic (ROC) Curve Analysis showed that blood and urinary TIM-3 mRNA expression level at month 3 and 6 could discriminate graft dysfunction (GD) from well-functioning graft (WFG) with high specificity and sensitivity. Conclusion Our data suggested that serial monitoring of TIM-3 mRNA level in the blood and urine samples of renal transplant recipients could be a useful non-invasive biomarker for prediction and diagnosis of allograft dysfunction.

The application of mesenchymal stem cells (MSCs) is rapidly expanding due to their unique properties in cell therapy, especially as the feeder layer in the ex-vivo expansion of immune cells. Also, Interleukin 2 (IL-2) is an essential human cytokine in the expansion of hematopoietic precursors and progenitors, i.e., NK cells and T cells, while there is no endogenous expression of IL-2 in MSCs. This study aimed to examine the potency of amniotic membrane (AM)-MSCs as the IL-2 secretory cells. IL-2-containing pCMV3-C-GFPspark shuttle vector was transformed in E.coli DH5-alpha. After cloning, the plasmid DNA was extracted and transfected in isolated AM-MSCs, by lipofectamine-2000. Then, the RNA and protein expression levels of exogenous IL-2 were evaluated 3 to 15 days after transfection, using ELISA and qRT-PCR. Fluorescent microscopy and flowcytometry assays were used for evaluating the GFP-positivity of transfected AM-MSCs, as IL-2 expression control. There was a significant increase in RNA expression of exogenous IL-2 in transfected AM-MSCs in 3 to 15 days after transfection. (p

Fast discrimination between quantum states of superconducting artificial atoms is an important ingredient for quantum information processing. In circuit quantum electrodynamics, increasing the signal field amplitude in the readout resonator, dispersively coupled to the artificial atom, improves the signal-to-noise ratio and increases the measurement strength. Here we employ this effect over two orders of magnitude in readout power, made possible by the unique combination of a dimer Josephson junction array amplifier with a large dynamic range, and the fact that the readout of our granular aluminum fluxonium artificial atom remained quantum-non-demolition (QND) at relatively large photon numbers in the readout resonator, up to $\overline{n} = 110$. Using Bayesian inference, this allows us to detect quantum jumps faster than the readout resonator response time $2/\kappa$, where $\kappa$ is the bandwidth of the readout resonator., Comment: main text: 5 pages + 4 figures. appendices: 3 pages + 3 figures

BACKGROUND: DNA methylation is an epigenetic modification that has the ability to alter gene expression and function. These epigenetic changes have been associated with the development of cancer. Previous research has found that DNA methylation patterns can predict disease prognosis for patients with Acute Promyelocytic Leukemia (APL). The role of DNMT1 and CDH1 in regulating the extension of cells are studied in this study. METHODS: DNA was extracted from peripheral blood samples of APL patients and treated with bisulfite. DNMT1 and CDH1 gene promoter methylation was subsequently analyzed using methylation-specific PCR (MSP). Real-time PCR was used to measure the expression level of DNMT1 and CDH1 genes. RESULTS: Partial methylation of the CDH1 gene promoter was detected in 20% of APL patients and an unmethylated status was detected in 80% of patient samples. Additionally, an unmethylated status in the DNMT1 gene promoter was detected in 100% of APL patient samples. CONCLUSION: Our study found the CDH1 gene promoter to be unmethylated in almost all APL patients, while the DNMT1 promoter was unmethylated in all APL patients. Furthermore, we observed an increase in both CDH1 and DNMT1 gene expression in APL patients compared to healthy controls. These findings suggest that DNMT1 may not have a specific role in inhibiting CDH1 gene expression in APL. Applying higher resolution techniques would help to better uncover the DNA methylation patterns in patients with APL. Further research is required to determine the role of DNA methylation and CDH1 and DNMT1 gene expression in APL.

Oxidative stress can worsen glycemic status. Considering the antioxidant properties of Ellagic acid (EA), this study was designed to evaluate the effect of EA on glycemic indices, lipid profile, oxidative stress, and inflammation status in type 2 diabetic patients. Overall, 44 patients were recruited and were randomly allocated consumed 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. The blood sugar (BS), insulin, insulin resistance (IR), hemoglobin A1c (HbA1 c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total antioxidant capacity (TAC), malondialdehyde (MDA), the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), C-reactive protein (CRP), TNF-α and interleukin 6 (IL-6) were measured at the beginning and end of the study. At the end of the study, the mean of BS, insulin, IR, HbA1 c, TC, TG, LDL, MDA, CRP, TNF-α, and IL-6 were significantly decreased in the intervention group (p < .05). Also, the mean of TAC (+0.8 ± 0.01) and activity of GPx (+10.26 ± 0.22) and SOD enzymes (+459.6 ± 9.76) significantly increased in the intervention group (p < .05). EA supplementation can be helpful as a diet supplement in patients with type 2 diabetes through improvement in chronic adverse effects.

17 pags., 9 figs., 3 tabs., 5 apps., Qubit readout is an indispensable element of any quantum information processor. In this work, we experimentally demonstrate a nonperturbative cross-Kerr couplingbetween a transmon and polariton mode which enables an improved quantum nondemolition (QND) readout for superconducting qubits. The new mechanism uses the same experimental techniques as the standard QND qubit readout in the dispersive approximation, but due to its nonperturbative nature, it maximizes the speed, the single-shot fidelity, and the QND properties of the readout. In addition, it minimizes the effect of unwanted decay channels such as the Purcell effect. We observe a single-shot readout fidelity of 97.4% for short 50-ns pulses and we quantify a QND-ness of 99% for long measurement pulses with repeated single-shot readouts., R. D. and S. L. acknowledge support from Fondation CFM pour la recherche. R. D., V. M., and O. B. acknowledge support from ANR REQUIEM (ANR-17-CE24-0012-01). J. J. G.-R. and T. R. acknowledge support from Project No. PGC2018-094792-B-I00 (MCIU/ AEI/FEDER, UE) and CAM/FEDER Project No. S2018/ TCS-4342 (QUITEMAD-CM). T. R. further acknowledges funding from the EU Horizon 2020 program under the Marie Skłodowska-Curie Grant Agreement No. 798397. S. L. acknowledges the Agence Nationale de la Recherche under the program Investissements d’avenir (ANR-15-IDEX02). K. B. and J. D. acknowledge the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754303. J. P. acknowledges grant from the Laboratoire d'excellence LANEF in Grenoble (ANR-10-LABX-51-01).

Background: MicroRNAs are a class of negative regulators of gene expression. Evidence indicates that miRNAs involved in the pathogenesis of New type 2 diabetes(NT2D) through decrease the expression of the genes secreting insulin and increase expression of insulin secretion suppressing ones, as well as exocytosis, incorporate in New type 2 diabetes. In this study, we evaluated the expression level of miR-135 in plasma sample of those prone to susceptible diabetes and New type 2 diabetes patients compared to the control group.Methods: Subsequently to evaluation of biochemical parameters such as (TG, TC, HDL, and LDL) in susceptible diabetes, New type 2 diabetes and control group, miR-135a level was measured by qRT-PCR in the plasma samples and results were analyzed by Stata and REST software.Results: We identified a significant increase in miR-135a expression in New type 2 diabetes and susceptible diabetes samples compared to the control group. AUC in ROC curve analysis was 1.1 respectively (confidence interval of 1.0-1.0) for NT2D and susceptible diabetes group, the best cut-off points for diagnostics in diabetics and susceptible diabetes were 2.00 and 1.02. The optimum sensitivity and specificity for both groups were 100 and 100. Results confirmed the test for 100% confidence in healthy, susceptible diabetes and New type 2 diabetes subjects.Conclusion: It seems that plasma level of miR-135a can be a desirable biomarker to differentiate T2DM diabetics from the control group.

This cohort intends to determine the sequential dynamic changes in Toll-like receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88 (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft recipients in relation to graft function. This study enrolled 52 renal transplant patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD). Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in relation to allograft function during one-year follow up. The mean dynamic changes of post-transplant TLR-2, TLR-4, and MYD88 mRNA expressions were significantly higher in GD compared to WFG patients (P = .001). ROC curve analysis based on glomerular filtration rate (GFR) index showed the area under curve (AUC) values for the genes: TLR-2(0.89;P < .001), TLR-4(0.86;P < .001), and MYD88(0.75;P = .003) in the third month post-transplantation for GD diagnosis. The calculated AUCs for the expressions of genes in allograft biopsies were 0.94(TLR-2), 0.95(TLR-4), and 0.98(MYD88) in the sixth month post-transplant based on pathology report (P < .001). Our results indicate that sequential monitoring of the expression patterns of TLR-2, TLR-4, and MYD88 in PBMCs and biopsy samples could be considered as predictive biomarkers for early and late kidney allograft function.

Objectives: Diabetes is one of the most important endocrine diseases caused by complex reactions between genetic and environmental factors. Recent studies have shown that microRNAs play an important role in the production, inhibition, and secretion of insulin. Identifying the relationship between key miRNAs that control the genes involved in the pathogenesis of diabetes is clinically important because it provides a way to identify preventive methods or treatments. In the present study, the expression of miR135a in serum samples between women with Gestational diabetes mellitus (GDM), non-pregnant type 2 diabetes, and healthy pregnant women were compared with the control group. Materials and methods: This study was a case-control study and non-random sampling method was used. The present study was conducted among four groups (healthy non-pregnant women (control), non-pregnant Diabetes type 2, GDM, and healthy pregnant). After serum separation, expression of miR-135a was measured using QRT-PCR technique and the results were analyzed by Stata and SPSS21 software. Results: The results show that the mean expression of miR-135a gene in control group was 0.9 ± 0.06, control of pregnancy was 1 ± 0.1, GDM group was 1.7 ± 0.3 and non-pregnant diabetic type 2 group was 6 ± 6 / 3. The results of analysis of variance showed that the mean difference of miR-135 gene expression was significant higher in the non- pregnant type 2 diabetes than GDM group (F = 2776.3, P

Background T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG). Methods We divided 85 patients into the following groups: AR (n = 24), CAD (n = 19), and WFG (n = 42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse-transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was used to measure the amount of KIM-1 protein in serum and urine samples. Results AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins compared to WFG patients. Receiver operating characteristic (ROC) analysis showed that these molecules discriminated Allograft rejections from WFG. Conclusion Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction.

Determining the state of a qubit on a timescale much shorter than its relaxation time is an essential requirement for quantum information processing. With the aid of a new type of non-degenerate parametric amplifier, we demonstrate the continuous detection of quantum jumps of a transmon qubit with 90% fidelity in state discrimination. Entirely fabricated with standard two-step optical lithography techniques, this type of parametric amplifier consists of a dispersion engineered Josephson junction (JJ) array. By using long arrays, containing $10^3$ JJs, we can obtain amplification at multiple eigenmodes with frequencies below $10~\mathrm{GHz}$, which is the typical range for qubit readout. Moreover, by introducing a moderate flux tunability of each mode, employing superconducting quantum interference device (SQUID) junctions, a single amplifier device could potentially cover the entire frequency band between 1 and $10~\mathrm{GHz}$., P.W. and I.T. contributed equally. 9 pages, 5 figures and appendices

We report on the fabrication and characterization of 50 Ohms, flux-tunable, low-loss, SQUID-based transmission lines. The fabrication process relies on the deposition of a thin dielectric layer (few tens of nanometers) via Atomic Layer Deposition (ALD) on top of a SQUID array, the whole structure is then covered by a non-superconducting metallic top ground plane. We present experimental results from five different samples. We systematically characterize their microscopic parameters by measuring the propagating phase in these structures. We also investigate losses and discriminate conductor from dielectric losses. This fabrication method offers several advantages. First, the SQUID array fabrication does not rely on a Niobium tri-layer process but on a simpler double angle evaporation technique. Second, ALD provides high quality dielectric leading to low-loss devices. Further, the SQUID array fabrication is based on a standard, all-aluminum process, allowing direct integration with superconducting qubits. Moreover, our devices are in-situ flux tunable, allowing mitigation of incertitude inherent to any fabrication process. Finally, the unit cell being a single SQUID (no extra ground capacitance is needed), it is straightforward to modulate the size of the unit cell periodically, allowing band-engineering. This fabrication process can be directly applied to traveling wave parametric amplifiers., Comment: 9 pages, 9 figures, Appendixes

We report on the implementation and detailed modelling of a Josephson Parametric Amplifier (JPA) made from an array of eighty Superconducting QUantum Interference Devices (SQUIDs), forming a non-linear quarter-wave resonator. This device was fabricated using a very simple single step fabrication process. It shows a large bandwidth (45 MHz), an operating frequency tunable between 5.9 GHz and 6.8 GHz and a large input saturation power (-117 dBm) when biased to obtain 20 dB of gain. Despite the length of the SQUID array being comparable to the wavelength, we present a model based on an effective non-linear LC series resonator that quantitatively describes these figures of merit without fitting parameters. Our work illustrates the advantage of using array-based JPA since a single-SQUID device showing the same bandwidth and resonant frequency would display a saturation power 15 dB lower., 12 pages, 9 figures, Appendices included

Background: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles. Methods: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction. Results: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes. Conclusion: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction.

Considering the two main categories of rapid single flux quantum gates with destructive and nondestructive readout process, we have investigated the effects of readout cell topology and involved critical parameters on the proper functionality and stability of the states of the newly developed bidirectional T flip-flops (TFFs). It is observed that instabilities and fluctuations in the state of the gate (memory of TFF) after each transition determine the minimum time intervals between the clock pulses set by the ac bias current, further limiting the ultimate operation frequency of the circuits. The absolute values of the current levels of the junctions at each state, which play an important role in the behavior of the cell, are studied, and their variations over several consequent pulses are stabilized by optimizing the cell parameters. The appropriate values of the circuit and junction parameters are found, resulting in the optimum operation of the circuit for having the best margins possible. We report on the investigated circuit topology and parameter optimizations of the readout circuit of the considered bidirectional TFF. © 2002-2011 IEEE.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to infections, autoimmunity and malignancies. This study was performed to analyze the Mannose-binding lectin (MBL) polymorphisms in Iranian patients with CVID. Thirty-five CVID patients who were treated at Children's Medical Center and 100 matched controls were enrolled in this study. Sixth single-nucleotide polymorphisms of the MBL gene were analyzed using PCR-SSP method. Comparison of MBL exon 1 coding alleles between patients and controls revealed that A allele (wild-type) was significantly decreased in CVID group, whereas B allele was overrepresented in the patient group. High frequency of heterozygous (A/O) in the patient group and high frequency of homozygous for wild-type coding regions in the control group were detected. Comparison of MBL haplotype promoters between CVID patients and controls showed that LYPB haplotype was significantly overrepresented in the CVID group. Mutant and low-producing MBL alleles and haplotypes might reflect as an associated genetic factor in CVID patients, which could play as a susceptibility factor in CVID.

There are several limitations on RSFQ circuit parameters determining their margins in critical conditions. We thoroughly investigated the sequential operation of the basic RSFQ circuits and study the corresponding behavior by comparing the measurable variables such as current response while modifying the eligible circuit's parameters. We introduce some figures of merit such as current level stability, current fluctuation damping after each pulse and circuit sensitivity, leading to obtain optimized parameters. A NDRO, cell based on T Flip-Flop (TFF), is particularly selected to verify the procedure. The optimized parameters are achieved by software simulation, considering the figures of merit. We also calculated the critical margins for main parameters in which the circuit is still remain stable.

Background MicroRNAs (miRNAs) regulate most of encoding genes and protein. In this study, we aimed to investigate the expression levels of miR-142-5p, miR-142-3p, miR-155 and miR-223 in paired biopsy and peripheral blood mononuclear cell (PBMC) samples of renal allograft recipients with acute T-cell mediated rejection (ATCMR), compared with normal allografts (NA). Methods In this study, the expression levels of individual miRNAs were determined in biopsy and PBMC samples of 17 recipients with ATCMR and 18 recipients with NA. Results Our results showed that the intragraft expression levels of all studied miRNAs were significantly higher in ATCMR than NA. However, regarding the PBMC samples, miR-142-3p and miR-223 were significantly increased in ATCMR than NA. Receiver operating characteristic (ROC) analysis showed that miR-142-5p, miR-142-3p, miR-155 and miR-223 in biopsy samples and miR-142-3p and miR-223 in PBMC samples could discriminate ATCMR from NA recipients. Conclusion It has been reported that high intragraft expressions of miRNAs have a profound role in the pathogenesis of ATCMR process. Our results showed that high expression of all the studied miRNAs in biopsies and miR-142-3p and miR-223 in PBMC samples could be used as suggestive diagnostic tools to discriminate ATCMR patients from NA.

Bi-directional RSFQ benefits from using both positive and negative SFQ pulses to manipulate and transfer digital data. This allows more flexibility in the design of simpler circuits with enhanced performance. On the other hand, using the AC bias current, one can replace on-chip resistive current distributors with inductors. This resembles RQL logic, but in contrast to RQL, it is possible to use the well-established standard RSFQ cells in bi-directional RSFQ. These two advantages (energy-efficient computation and flexibility in design) make bi-directional RSFQ a powerful tool in next-generation supercomputers and also compatible with ultra-low-temperature quantum computers. In this work, to show the power and simplicity of circuits in bi-directional RSFQ, a fully digital SQUID based on bi-directional RSFQ is designed and optimized. The circuit we show here is a delta modulating ADC with digital integrator. The circuit has fewer Josephson junctions than other reported circuits, which makes the proposed circuit more easily realizable in available LTc and HTc technologies.