Cohen syndrome combined with psychiatric symptoms: a case report.

BACKGROUND: Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms. CASE REPORT: We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms. CONCLUSIONS: This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.

Mechanical Properties and Crack Resistance of Basalt Fiber Self-Compacting High Strength Concrete: An Experimental Study.

Pure self-compacting concrete has many disadvantages, such as early shrinkage and cracking. The addition of fibers can effectively improve the properties of resistance to tension and cracking of self-compacting concrete, thereby the effect of improving its strength and toughness can be achieved. Basalt fiber is a "new green industrial material" that has unique advantages, such as high crack resistance and being lightweight compared with other fiber materials. In order to study the mechanical properties and crack resistance of basalt fiber self-compacting high-strength concrete intensively, the self-compacting high-strength concrete of C50 was designed and obtained using the absolute volume method with multiple proportions. Orthogonal experimental methods were used to study the influence of the water binder ratio, fiber volume fraction, fiber length, and fly ash content on the mechanical properties of the basalt fiber self-compacting high-strength concrete. Meanwhile, the efficiency coefficient method was used to determine the best experiment plan (water binder ratio 0.3, fiber volume ratio 0.2%, fiber length 12 mm, fly ash content 30%), and the effect of fiber volume fraction and fiber length on the crack resistance of the self-compacting high-performance concrete was investigated using improved plate confinement experiments. The results show that (1) the water binder ratio had the greatest impact on the compressive strength of basalt fiber self-compacting high-strength concrete, and as the fiber volume fraction increased, the splitting tensile strength and flexural strength both increased; (2) there was an optimal value for the effect of the fiber length on the mechanical properties; (3) with the increase in fiber volume fraction, the total crack area of the fiber self-compacting high-strength concrete significantly decreased. When the fiber length increased, the maximum crack width first decreased and then slowly increased. The best crack resistance effect was achieved when the fiber volume fraction was 0.3% and the fiber length was 12 mm. Therefore, basalt fiber self-compacting high-strength concrete can be widely used in engineering fields, such as national defense construction, transportation, and building structure reinforcement and repair, due to its excellent mechanical and crack resistance properties.

Study on mechanical properties of corroded concrete columns strengthened with SMA wires.

Ocean crossing bridges suffer from seawater corrosion all year round and their mechanical properties will be substantially diminished. In order to enhance the mechanical properties of reinforced concrete columns corroded by seawater, SMA wire is used to restrain the reinforced concrete columns corroded by seawater to study their mechanical properties. 14 specimens were produced through the test, and the natural seawater corrosion was simulated by preparing a certain concentration of synthetic seawater. The mechanical properties of SMA strengthened specimens and unreinforced specimens are compared and analyzed, including failure mode, hysteresis curve, bearing capacity, ductility, stiffness and energy dissipation; the effects of different synthetic seawater corrosion concentrations on the mechanical properties of reinforced concrete columns are discussed. The results show that the bearing capacity and stiffness of reinforced concrete columns subjected to synthetic seawater corrosion are substantially diminished than those of uncorroded specimens, and the bearing capacity of specimens decreases more with the increase of synthetic seawater corrosion concentration; synthetic seawater corrosion has obscure effect on the ductility and energy dissipation performance of the specimens. The mechanical properties of the corroded specimens strengthened with SMA wire have been substantially enhanced, particularly the energy dissipation performance and bearing capacity have been notably enhanced, and the ductility and stiffness have also been somewhat enhanced. At the same time, based on the test, the finite element model is created according to the test specimen, while the accuracy of the model is verified, and the effects of the spacing and diameter of SMA wire, the strength of concrete and the thickness of protective layer on the mechanical properties of the specimen are analyzed.

Law of coal caving behind the flexible shield support in pseudo-inclined working face.

Complex boundary conditions are the major influencing factors of coal caving law in the pseudo-inclined working face. The main purpose of this study is to analyze coal caving law of flexible shield support and then to establish the internal relations among coal caving parameters under complex boundary conditions. Firstly, the law of coal caving in different falling modes is simulated physically. Secondly, the coal caving shape, displacement field, and contact force field is simulated. Then, coal caving law and process parameters is analyzed theoretically. Finally, the test was performed in Bai-Ji Mine. The research shows that ellipsoidal ore drawing theory has universal applicability in coal drawing law analysis and parameter optimization. After the Isolated Extraction Zone and Isolated Movement Zone reach the roof, the expansion speed is marked by a short delay, and then, while expanding to the floor, two butted incomplete ellipsoids are formed. There is a time-space difference in coal caving after the support, and some coal will be mined in the next round of coal caving. There are obvious differences in the coal loosening range, displacement field, and contact force field on both sides of the long axis. When the support falls along with the bottom plate, it is more conducive to the release of coal. The test shows that the research is of great significance for optimizing the caving parameters of flexible shield support in the pseudo-inclined working face of the steep seam.

Copy number variation analysis of m6 A regulators identified METTL3 as a prognostic and immune-related biomarker in bladder cancer.

PURPOSE: Growing evidence has demonstrated an indispensable role for N6 -methyladenosine (m6 A) in human diseases, but the copy number variations (CNVs) of m6 A regulatory genes in bladder cancer (BLCA) remains largely unknown. METHODS: We investigated the CNVs on all known m6 A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6 A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. RESULTS: CNV events of m6 A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer-related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6 A regulatory genes were correlated with specific kinds of immune infiltrates. CONCLUSIONS: There are significant correlations between m6 A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

Development and Validation of a Prognostic Classifier Based on Lipid Metabolism-Related Genes in Gastric Cancer.

Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism-related genes in GC patients. Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors. Results: A risk predictive score model was established based on the expression of 19 lipid metabolism-related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high-risk and low-risk score groups. A nomogram containing patients' age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years. Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism-related genes, which could be a potential prognostic indicator and therapeutic target of GC.

Inhibition of NLRC5 regulates cytokine expression in CD4+ T helper lymphocytes and prolongs murine islet and skin allograft survival.

The purpose of this study was to study the effect of inhibiting NLRC5 expression and function on CD4 + T cells, and islet and skin transplantation in mice. A murine skin graft model and islet cell transplantation model were established, and the expression of NLRC5 was compared in rejection and immune tolerance groups. Mice spleen-derived CD4 + T cells were cultured, purified, and enriched in vitro, and transfected with the shRNA lentiviral vector NLRC5-RNAi-GFP. Changes in cytokine secretion were detected to understand changes in immunological function. Murine islet and skin transplantation models were injected with CD4 + T cells transfected with the lentivirus, and the survival time of the grafts and the levels of IFN-γ and IL-10 were compared between groups. The expression of NLRC5 mRNA in islet and skin grafts was significantly increased. In vitro experiments showed that the expression of IL-4 and IL-10 was up-regulated in CD4 + T cells, and T cells differentiation turned to Th2 after inhibition of NLRC5. In vivo experiments showed that inhibition of NLRC5 prolonged islet and skin graft survival. Pathological examination showed that the rejection of transplanted skin and islets in the NLRC5-RNAi group was mild, and there was a correlation between high expression of NLRC5 and rejection of mouse islet and skin grafts. In summary, inhibition of NLRC5 can prolong islet and skin graft survival induce transplant immune tolerance through induction of the secretion of Th2 cytokines by CD4 + T cells.

Expression and prognostic value of transcription-associated cyclin-dependent kinases in human breast cancer.

The expression and prognostic significance of transcription-associated cyclin-dependent kinases (TA-CDKs) in breast cancer have not been systematically investigated. Using Oncomine, GEPIA2, the Human Protein Atlas, the Kaplan-Meier Plotter, cBioPortal, Metascape, and DAVID 6.8, we profiled the expression of TA-CDKs in breast cancer, inferred their biological functions, and assessed their effect on prognosis. The expression of CDK7/10/13/19 mRNAs in breast cancer tissues was significantly higher than in normal breast tissues. Survival analysis of breast cancer patients revealed that increased CDK8 expression was associated with inferior overall survival (OS), higher expression of CDK7 or CDK8 was associated with inferior relapse-free survival (RFS), but higher expression of CDK13 was associated with favorable RFS and OS. In addition, a high genetic alteration rate (56%) in TA-CDKs was associated with shorter OS. On functional enrichment analysis, top GO enrichment items for TA-CDKs and their neighboring genes included cyclin-dependent protein serine/threonine kinase activity and transferase complex. The top KEGG pathways included cell cycle and mismatch repair. These results suggest that CDK7/8/13 are potential prognostic biomarkers for breast cancer patients and provide novel insight for future studies examining their usefulness as therapeutic targets.

Multi-omics analysis of copy number variations of RNA regulatory genes in soft tissue sarcoma.

AIMS: RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, little is known regarding their possible roles in STS. MAIN METHODS: RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines. KEY FINDINGS: CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib. SIGNIFICANCE: CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.

Enhanced Quarter Spherical Acoustic Energy Harvester Based on Dual Helmholtz Resonators.

An enhanced quarter-spherical acoustic energy harvester (AEH) with dual Helmholtz resonators was designed in this work. Compared with the previous research, this AEH can harvest multi-directional acoustic energy, has a widened resonance frequency band, and has an improved energy conversion efficiency. When the length of resonator's neck is changed, the acoustic resonant frequency of the two resonators is different. The theoretical models of output voltage and output power were studied, and the relationship of output performance with frequency was obtained. The results showed that this AEH can operate efficiently in a frequency band of about 470 Hz. Its output voltage was found to be about 28 mV, and its output power was found to be about 0.05 µW. The power density of this AEH was found to be about 12.7 µW/cm2. Therefore, this AEH could be widely used in implantable medical devices such as implantable cardiac pacemakers, cochlear implants, and retinal prosthesis.

Development and validation of metabolism-related gene signature in prognostic prediction of gastric cancer.

Gastric cancer is one of the most common malignant tumours in the world. As one of the crucial hallmarks of cancer reprogramming of metabolism and the relevant researches have a promising application in the diagnosis treatment and prognostic prediction of malignant tumours. This study aims to identify a group of metabolism-related genes to construct a prediction model for the prognosis of gastric cancer. A large cohort of gastric cancer cases (1121 cases) from public database was included in our analysis and classified patients into training and testing cohorts at a ratio of 7: 3. After identifying a list of metabolism-related genes having prognostic value, we constructed a risk score based on metabolism-related genes using LASSO-COX method. According to the risk score, patients were divided into high- and low-risk groups. Our results revealed that high-risk patients had a significantly worse prognosis than low-risk patients in both the training (high-risk vs low-risk patients; five years overall survival: 37.2% vs 72.2%; p < 0.001) and testing cohorts (high-risk vs low-risk patients; five years overall survival: 42.9% vs 62.9%; p < 0.001). This observation was validated in the external validation cohort (high-risk vs. low-risk patients; five years overall survival: 30.2% vs 40.4%; p = 0.007). To reinforce the predictive ability of the model, we integrated risk score, age, adjuvant chemotherapy, and TNM stage into a nomogram. According to the result of receiver operating characteristic curves and decision curves analysis, we found that the nomogram score had a superior predictive ability than conventional factors, indicating that the risk score combined with clinicopathological features can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified a list of metabolic genes related to survival and developed a metabolism-based predictive model for gastric cancer. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was confirmed.

Synergistic therapeutic effect of combined PDGFR and SGK1 inhibition in metastasis-initiating cells of breast cancer.

Lack of insight into the identity of the cells that initiate metastasis hampers the development of antimetastatic therapies. Only a tiny fraction of tumor cells termed metastasis-initiating cells (MICs) are able to successfully seed metastases, causing recurrence and therapeutic resistance. Using metastasis models, we describe a subpopulation of MIC derivates from lung metastases that do not have proliferation advantages, express high levels of the PDGF receptors and EMT/stemness-related genes, and are unique in their ability to initiate metastasis. PDGF factors specifically boost the metastatic potential of MIC populations in a PDGFR-dependent manner. However, PDGFR inhibition preferentially suppresses lung metastases, but does not reduce the primary tumor burden. Thus, we found that PDGFR inhibition blocks AKT activation, whereas SGK1, which shares high-similarity kinase domain and overlap substrates with AKT overexpression remains active in MICs. SGK1 and PDGF signaling act in concert to promote metastatic formation, and SGK1 inhibition confers vulnerability to PDGFR inhibitors, also eliciting a powerful antitumor effect. In vivo, SGK1 inhibitors sensitize xenograft tumors to PDGFR-targeted therapies by reducing primary tumor growth and lung metastasis. Consequently, dual inhibition of PDGFR and SGK1 exhibited strong antitumor activities in established breast cancer cell lines in vitro and in vivo. Therefore, this approach not only provides insight into MIC transformation but also aids the design of improved therapeutic strategies for advanced breast cancer.

Analysis of portal vein thrombosis after liver transplantation.

BACKGROUND: Portal vein thrombosis (PVT) is one of the most deadly complications after orthotopic liver transplantation (OLT). This study aimed to identify risk factors and summarize the experience of PVT management after OLT. METHODS: The clinical data of 407 adult patients received OLT from July 2011 to December 2015 was retrospectively investigated. RESULTS: The incidence rate of PVT was 2.9% (12/407). Pre-transplant PVT (P = 0.001), post-operative transfusion of erythrocyte (P = 0.006) and platelet (P = 0.036) were significantly associated with PVT in the univariate analysis and the appearance of pre-transplant PVT (P = 0.002, odds ratio 6.05) was the independent risk factor according to binary logistic regression. Among patients with PVT, three cases (3/12) received balloon dilation through selective catheterization of portal vein, five (5/12) received balloon-expandable stent placement, three (3/12) received thrombectomy and surgical revascularization and one (1/12) received retransplantation. Six patients (6/12) died from various complications and the remaining six were followed up with normal liver function and patent portal vein. CONCLUSIONS: The risk factors were pre-transplant PVT and post-operative transfusion of erythrocyte and platelet. To recipients with high risk, early diagnosis and prompt management of PVT are essential to improve prognosis.

circRAD18 sponges miR-208a/3164 to promote triple-negative breast cancer progression through regulating IGF1 and FGF2 expression.

As a new rising star of non-coding RNA, circular RNAs (circRNAs) emerged as vital regulators with biological functions in diverse of cancers. However, the function and precise mechanism of the vast majority of circRNAs in triple-negative breast cancer (TNBC) occurrence and progression have not been clearly elucidated. In the current study, we identified and further investigated hsa_circ_0002453 (circRAD18) by analyzing our previous microarray profiling. Expression of circRAD18 was found significantly upregulated in TNBC compared with normal mammary tissues and cell lines. circRAD18 was positively correlated with T stage, clinical stage and pathological grade and was an independent risk factor for TNBC patients. We performed proliferation, colony formation, cell migration, apoptosis and mouse xenograft assays to verify the functions of circRAD18. Knockdown of circRAD18 significantly suppressed cell proliferation and migration, promoted cell apoptosis and inhibited tumor growth in functional and xenograft experiments. Through luciferase reporter assays, we confirmed that circRAD18 acts as a sponge of miR-208a and miR-3164 and promotes TNBC progression through upregulating IGF1 and FGF2 expression. Altogether, our research revealed the pivotal role of circRAD18-miR-208a/3164-IGF1/FGF2 axis in TNBC tumorigenesis and metastasis though the mechanism of competing endogenous RNAs. Thus, circRAD18 may serve as a novel prognostic biomarker and potential target for TNBC treatment in the future.

Management of hepatic vein occlusive disease after liver transplantation: A case report with literature review.

RATIONALE: Hepatic vein occlusive disease (HVOD) is a rare complication after liver transplantation, which is characterized by nonthrombotic, fibrous obliteration of the small centrilobular hepatic veins by connective tissue and centrilobular necrosis in zone 3 of the acini. HVOD after solid organ transplantation has been reported; recently, most of these reports with limited cases have documented that acute cell rejection and immunosuppressive agents are the major causative factors. HVOD is relatively a rare complication of liver transplantation with the incidence of approximately 2%. PATIENT CONCERNS: A 59-year-old male patient with alcoholic liver cirrhosis underwent liver transplantation in our center. He suffered ascites, renal impairment 3 months after the surgery while liver enzymes were in normal range. DIAGNOSES: Imagining and pathology showed no evidence of rejection or vessels complications. HVOD was diagnosed with pathology biopsy. INTERVENTIONS: Tacrolimus was withdrawn and the progression of HVOD was reversed. OUTCOMES: Now, this patient has been followed up for 6 months after discharge with normal liver graft function. LESSONS: The use of tacrolimus in patients after liver transplantation may cause HVOD. Patients with jaundice, body weight gain, and refractory ascites should be strongly suspected of tacrolimus related HVOD.

Analysis of early hepatic artery thrombosis after liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is one of the deadliest complications after orthotopic liver transplantation (OLT). This study aimed to identify risk factors and summarize the experience of HAT management after OLT. METHODS: Clinical data of 407 adult patients who received OLT in our centres from July 2011 to December 2015 were retrospectively investigated. RESULTS: The incidence rate of early HAT was 2.0% (8/407). Recipient/donor weight ratio ≥1.15 (P = 0.02), presence of hepatic arterial reconstruction (P < 0.001) and post-operative blood transfusion (P = 0.001) were significantly associated with early HAT in the univariate analysis and the only independent risk factor (odds ratio = 28.49) in binary logistic regression was the presence of hepatic arterial reconstruction. Among patients with early HAT, five received interventional revascularization while two received surgical revascularization and the remaining one received re-transplantation. Their liver grafts were functioning well with patent hepatic artery until their last follow-up, whereas one died from tumor recurrence at 31st month after transplantation. CONCLUSION: The presence of hepatic arterial reconstruction, recipient/donor weight ratio ≥1.15 and post-operative blood transfusion were the main risk factors associated with early HAT. Prompt recognition of these factors, strict surveillance protocols and selective anticoagulation for patients at risk need to be evaluated. For patients with early HAT occurring within a week after transplantation, surgical re-arterialization is preferential while interventional revascularization is recommended when it occurs beyond 7 days after transplantation.

Dendritic Cells Transduced with Single Immunoglobulin IL-1-Related Receptor Exhibit Immature Properties and Prolong Islet Allograft Survival.

Members of toll-like receptor-interleukin 1 receptor signaling [TLR/IL-1R (TIR)] superfamily mediate maturation of dendritic cells (DCs) and launch immune response in transplanted organs. In this study, we hypothesized that TIR8, also known as single immunoglobulin IL-1-related receptor (SIGIRR) molecule, refrain DCs from maturation and induce immune tolerance of transplanted organ. DCs were transduced with the recombinant adenovirus Ad5F35 to highly express SIGIRR (DC-SIGIRR), then injected to murine recipient before islet transplantation. It revealed that DCs transduced with SIGIRR had low expression of major histocompatibility and costimulatory molecules along with strong phagocytic ability in vitro assay. The data demonstrated that recipients treated with DC-SIGIRR had satisfying islet allograft function and long survival times, with an increase of Treg and reduction of Th17 in both spleen and draining lymph nodes in vivo. Therefore, genetic modification of SIGIRR inhibits DC activation and maturation, affects differentiation of T cell subsets, protects allograft biological function, and prolongs graft survival.

Dendritic cells that highly express SOCS1 induce T-cell hypo-responsiveness and prolong islet allograft survival.

The capability of dendritic cells (DCs) to induce an immune response or immune tolerance is dependent on their status. Suppressor of cytokine signaling 1 (SOCS1) is a pivotal regulator that participates in negative feedback of the JAK-STAT pathway, which plays a key role in the differentiation, activation, and maturation of DCs. DCs that highly express SOCS1 may modulate DCs, and induce immune anergy or immune tolerance. In this study, we transduced DCs with the recombinant adenovirus Ad5F35 to highly express SOCS1. The mechanisms by which DC-SOCS1 induces T-cell hypo-responsiveness were analyzed in vivo and in vitro. The data demonstrate that recipients treated with DC-SOCS1 had long islet allograft survival times, with a reduction of Th1 and Tc1 in both spleen and draining lymph nodes in vivo. In vitro assay revealed that DCs transduced with SOCS1 had low expression of major histocompatibility and costimulatory molecules, and potentiated the ability of DC-SOCS1 to induce T-cell hypo-responsiveness. Therefore, genetic modification of DCs with SOCS1 affects DC activation and maturation, inhibits T-cell proliferation and induces hypo-responsiveness, and prolongs islet allograft survival.