Architectural protein subclasses shape 3D organization of genomes during lineage commitment.

Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here, we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3D interactions that undergo marked reorganization at the submegabase scale during differentiation. Distinct combinations of CCCTC-binding factor (CTCF), Mediator, and cohesin show widespread enrichment in chromatin interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant subdomains. Conversely, Mediator/cohesin bridge short-range enhancer-promoter interactions within and between larger subdomains. Knockdown of Smc1 or Med12 in embryonic stem cells results in disruption of spatial architecture and downregulation of genes found in cohesin-mediated interactions. We conclude that cell-type-specific chromatin organization occurs at the submegabase scale and that architectural proteins shape the genome in hierarchical length scales.

Retrospective cohort evaluation of non-HIV Castleman disease from a single academic center in Beijing, China.

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).

Activation of Young LINE-1 Elements by CRISPRa.

Long interspersed element-1 (LINE-1; L1s) are mobile genetic elements that comprise nearly 20% of the human genome. L1s have been shown to have important functions in various biological processes, and their dysfunction is thought to be linked with diseases and cancers. However, the roles of the repetitive elements are largely not understood. While the CRISPR activation (CRISPRa) system based on catalytically deadCas9 (dCas9) is widely used for genome-wide interrogation of gene function and genetic interaction, few studies have been conducted on L1s. Here, we report using the CRISPRa method to efficiently activate L1s in human L02 cells, a derivative of the HeLa cancer cell line. After CRISPRa, the young L1 subfamilies such as L1HS/L1PA1 and L1PA2 are found to be expressed at higher levels than the older L1s. The L1s with high levels of transcription are closer to full-length and are more densely occupied by the YY1 transcription factor. The activated L1s can either be mis-spliced to form chimeric transcripts or act as alternative promoters or enhancers to facilitate the expression of neighboring genes. The method described here can be used for studying the functional roles of young L1s in cultured cells of interest.

Isolation and Characterization of Germline Stem Cells in Protogynous Hermaphroditic Monopterus albus.

Germline stem cells (GSCs) are a group of unique adult stem cells in gonads that act as important transmitters for genetic information. Donor GSCs have been used to produce offspring by transplantation in fisheries. In this study, we successfully isolated and enriched GSCs from the ovary, ovotestis, and testis of Monopterus albus, one of the most important breeding freshwater fishes in China. Transcriptome comparison assay suggests that a distinct molecular signature exists in each type of GSC, and that different signaling activities are required for the maintenance of distinct GSCs. Functional analysis shows that fGSCs can successfully colonize and contribute to the germline cell lineage of a host zebrafish gonad after transplantation. Finally, we describe a simple feeder-free method for the isolation and enrichment of GSCs that can contribute to the germline cell lineage of zebrafish embryos and generate the germline chimeras after transplantation.

MYC/MAX control ERK signaling and pluripotency by regulation of dual-specificity phosphatases 2 and 7.

Suppression of extracellular signal-regulated kinase (ERK) signaling is an absolute requirement for the maintenance of murine pluripotent stem cells (mPSCs) and requires the MYC-binding partner MAX. In this study, we define a mechanism for this by showing that MYC/MAX complexes suppress ERK activity by transcriptionally regulating two members of the dual-specificity phosphatase (DUSP) family. DUSPs function by binding and then inactivating ERK1,2 by dephosphorylating residues required for catalytic activity. MYC/MAX complexes achieve this by binding the promoters of DUSP2 and DUSP7, leading to their transcriptional activation, resulting in the attenuation of ERK activity. In the absence of MYC, ectopic DUSP2,7 expression severely delays differentiation, while loss of DUSP2,7 ectopically activates ERK, resulting in loss of pluripotency. These findings elucidate a novel regulatory role for MYC in PSC maintenance involving the stimulation of phosphatases that directly inhibit the MAPK/ERK signaling pathway. Moreover, it provides a mechanism for how leukemia inhibitory factor (LIF)/STAT3 signaling reaches across to the MAPK/ERK pathway through MYC and MAX to sustain pluripotency.

PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction.

Cardiac development is a complex process that is strictly controlled by various factors, including PcG protein complexes. Several studies have reported the critical role of PRC2 in cardiogenesis. However, little is known about the regulation mechanism of PRC1 in embryonic heart development. To gain more insight into the mechanistic role of PRC1 in cardiogenesis, we generated a PRC1 loss-of-function zebrafish line by using the CRISPR/Cas9 system targeting rnf2, a gene encoding the core subunit shared by all PRC1 subfamilies. Our results revealed that Rnf2 is not involved in cardiomyocyte differentiation and heart tube formation, but that it is crucial to maintaining regular cardiac contraction. Further analysis suggested that Rnf2 loss-of-function disrupted cardiac sarcomere assembly through the ectopic activation of non-cardiac sarcomere genes in the developing heart. Meanwhile, Rnf2 deficiency disrupts the construction of the atrioventricular canal and the sinoatrial node by modulating the expression of bmp4 and other atrioventricular canal marker genes, leading to an impaired cardiac conduction system. The disorganized cardiac sarcomere and defective cardiac conduction system together contribute to defective cardiac contraction. Our results emphasize the critical role of PRC1 in the cardiac development.

Impact of Drying Methods on Phenolic Components and Antioxidant Activity of Sea Buckthorn (Hippophae rhamnoides L.) Berries from Different Varieties in China.

Sea buckthorn berries are rich in bioactive compounds and can be used for medicine and food. The variety and drying method used have an important influence on quality. In this study, different sea buckthorn varieties from China were selected and dried with four common drying methods. The total phenolic content (TPC), total flavonoids content (TFC), contents of 12 phenolic compounds and antioxidant capacity in vitro were analyzed. The results showed that the TPC, TFC and antioxidant activity of two wild sea buckthorn berries were higher than those of three cultivated berries, and for the same varieties, measured chemical contents and antioxidant activity of the freeze-dried fruit were significantly higher than those obtained with three conventional drying methods. In addition, forty-one compounds in sea buckthorn berry were identified by UPLC-PDA-Q/TOF-MS, most of which were isorhamnetin derivatives. Multivariate statistical analysis revealed narcissin and isorhamnetin-3-O-glucoside varied significantly in sea buckthorn berries of different varieties and with different drying methods; they were potential quality markers. Strong correlations were found between TPC, gallic acid and antioxidant capacity (p < 0.05). The results revealed how components and antioxidant activity varied in different sea buckthorn, which provides a valuable reference for quality control and further development and utilization of sea buckthorn.

The predictive value of serum free light chain level early after allogeneic hematopoietic stem cell transplantation for chronic graft-versus-host disease, a preliminary study.

OBJECTIVE: Serum free light chain (FLC) level is closely associated with the functional state of B lymphocytes, and many studies have shown that delayed reconstitution of B lymphocytes contributed to chronic graft-versus-host disease (cGVHD). This study assessed the predictive value of FLC levels in serum collected early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for cGVHD. METHODS: Sixty-two patients who had undergone allo-HSCT were retrospectively reviewed. The correlations between the FLC levels and the development of cGVHD were explored. RESULTS: Of the 62 patients, 33 cases developed cGVHD, with the prevalence of 53.2%. With Seattle classification, 19 cases had limited cGVHD while 14 cases contracted extensive cGVHD. While with NIH classification, 17 cases had mild cGVHD, 6 cases moderate cGVHD, and 10 cases severe cGVHD. Multivariant statistical analysis showed that the FLC levels were not associated with all severities of cGVHD but were correlated with the development of extensive or moderate to severe cGVHD (P = .01 and .038, respectively). CONCLUSIONS: Serum FLC levels early after HSCT may reflect the functional state of B-cell reconstitution. Patients with low serum FLC Level early post-allo-HSCT tend to develop extensive cGVHD or moderate to severe cGVHD.

[Mutational analysis of 117 patients with non-syndromic hearing loss].

OBJECTIVE: To determine the frequencies of deafness gene mutations among patients with non-syndromic hearing loss (NSHL) from northern Jiangsu province. METHODS: A total of 117 patients with NSHL were enrolled. The coding region of GJB2 gene, IVS7-2A>G and 2168A>G mutations of SLC26A4 gene, and 1555A>G and 1494C>T mutations of mitochondrial DNA 12S rRNA were subjected to Sanger sequencing. Patients in whom no mutation was detected were further tested by targeted gene capture and high-throughput sequencing. RESULTS: Among the 117 patients, 86 (73.50%) were found to carry mutations. GJB2 gene mutations were found in 61 patients (52.14%), including 22 (18.80%) with homozygous mutations and 39 (33.33%) with heterozygous mutations. SLC26A4 gene mutations were found in 19 patients (16.24%), including 4 (3.42%) with homozygous mutations and 15 with heterozygous mutations (14.53%). Mitochondrial 12S rRNA gene mutation was found in 6 patients (5.13%). Targeted gene capture and high-throughput sequencing of 8 patients identified 4 further cases, including 1 with RDX gene 129_130del and 76_79del compound heterozygous mutations, 1 with OTOF gene 1274G>C homozygous mutation, 1 with SLC26A4 gene 919-2A>G and IVS16-6G>A compound heterozygous mutation, and 1 with SLC26A4 gene 919-2A>G and A1673T compound heterozygous mutation. CONCLUSION: The frequency of mutation among patients with NSHL from north Jiangsu was 73.50%, and GJB2 gene was most commonly mutated.

Alterations of CCR5 and CCR7 expression on donor peripheral blood T cell subsets after mobilization with rhG-CSF correlate with acute graft-versus-host disease.

To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on chemokine receptors and explore the potential mechanism of rhG-CSF inducing immune tolerance, ninety-seven donor and recipient pairs undergoing family-donor allogeneic hematopoietic stem cell transplantation were studied. The results indicated that different donors showed great disparities in expression changes after mobilization. Multivariate analysis revealed that both HLA mismatching and CCR7 downregulation on donors' CD4+ T cells after mobilization were independent risk factors for acute graft-versus-host disease (GVHD). In contrast, CCR5 downregulation on CD4+ T cells was associated with reduced incidence of acute GVHD. In conclusion, rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets in different donors. Downregulation of CCR5 and upregulation of CCR7 expression on donor CD4+ T cells might protect recipients from acute GVHD. This finding may provide a promising new strategy for the prevention and treatment of acute GVHD.

Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury.

BACKGROUND: Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury. RESULTS: Spp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway. CONCLUSIONS: Spp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.

Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor.

This study retrospectively collected the clinical and laboratory data of 114 patients with Castleman disease (CD) from a single medical centre. Clinical classification identified 62 patients (54·4%) with unicentric Castleman disease and 52 (45·6%) with multi-centric Castleman disease. Pathological classification revealed 68 cases (59·6%) of hyaline vascular variant, 16 (14·1%) mixed cellular variant (Mix) and 30 (26·3%) plasmacytic variant. Clinical complications occurred in 69 CD patients, including 37 cases of paraneoplastic pemphigus (PNP) and 25 cases with renal complications. Haematological involvement, pleural effusion and/or ascites and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) were also found. Univariate analysis showed that presence of clinical complications and PNP were both risk factors relating to CD patient survival. Prognostic factors showing P < 0·15 in univariate analysis and those with clinical significance were subjected to multivariate analysis using a Cox regression model. PNP presence and age over 40 years both significantly adversely affected survival. Thus, only presence of PNP was identified as an independent unfavourable survival risk factor in both univariate and multivariate analyses. Overall, the present data provide a panoramic description of CD cases and emphasize that the presence of PNP is an adverse prognostic factor.

Fucus extract: cosmetic treatment for under-eye dark circles.

BACKGROUND: Dark circles around the eyes are a complex issue with two main possible causes, the accumulation of melanin in the skin around the eyes and the accumulation of heme resulting from blood leakage. The free heme produced in this manner is highly cytotoxic, proinflammatory and pro-oxidative. AIMS: To evaluate the effect of Fucus extract on heme oxygenase-1 (HO-1) stimulation activity, and to study its in vitro anti-inflammatory, antioxidative, and collagen stimulation activity. METHODS: The HO-1 stimulation activity was first evaluated at gene level by reverse transcriptase- polymerase chain reaction targeting specific HO-1 gene, and then followed by Western blot in protein level. The in vitro anti-inflammatory effect was measured by quantification of interleukin-8 (IL-8) level. The in vitro antioxidative activity was measured. Collagen stimulation activity was quantitatively measured by the amount of deposited collagen I in the extracellular matrix. RESULTS: Fucus extract was identified to have HO-1 stimulation activity at both gene and protein level. By stimulating this enzyme, it promotes the degradation of toxic heme to its protective catabolites (CO, Ferritin, and bilirubin) and reduces the source of dark circles. In addition, Fucus extract showed good anti-inflammatory efficacy. The strong antioxidation property of Fucus extract can reduce eye bags and wrinkles while its collagen boosting activity will potentially reduce fine lines and wrinkles. CONCLUSION: Fucus extract is a novel product that brings a quadruple approach to the treatment of under-eye dark circles.

[The clinical characteristics of polyserositis as main presentation of chronic graft-versus-host rejection disease after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To analyze the clinical characteristics of polyserositis associated with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic transplantation(allo-HSCT). METHODS: The occurrence rate and severity of cGVHD in 323 patients who received allo-HSCT in Peking University First Hospital from June 2003 to July 2013 were observed. Their clinical characteristics and therapeutic effect on polyserositis were analyzed as well. RESULTS: Of the 294 patients who survived for more than 100 days after allo-HSCT, 90 patients (30.6%) were diagnosed with cGVHD including extensive cGVHD in 25 patients (8.5%). Among the patients with cGVHD, 4 patients (4.4%) developed moderate to large amount of polyserous effusions. All of these 4 patients had extensive cGVHD. The effusion was proved to be transudate or transudate-exudate. Immunosuppressive treatment was effective but unsustainable. CONCLUSIONS: Polyserositis with large amount of effusion might be a rare manifestation of cGVHD and is refractory. When recurrent polyserous effusion presents with cGVHD after allo-HSCT, it should be considered as a manifestation of extensive cGVHD. Appropriate treatment should be given immediately.

[The influence of liver dysfunction before transplantation and during conditioning period on the outcome of allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the characteristics of liver dysfunction pre-transplant and during conditioning period and its impacts on transplantation related hepatic complication, overall survival (OS) and transplant-related mortality (TRM). METHODS: A total of 196 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Peking University First Hospital were analyzed retrospectively. Liver function test for each patient was examined pre-transplant and during the period of conditioning. The correlation of liver dysfunction with hepatic complications, OS and TRM rates were analyzed. RESULTS: Liver dysfunction before transplantation was found in 38 (19.8%, 38/192) patients, while damage of liver function during conditioning was found in 159(81.1%) patients, 28 of whom developed grade 3 hepatic dysfunction. There was no life-threatening impairment of liver function. No matter pre-transplant or during conditioning, liver dysfunction did not suggest apparent influence on the engraftment of neutrophil or platelet or the incidence of hepatic complications including hepatic veno occlusive disease (HVOD), acute graft versus host disease (aGVHD) and chronic graft versus host disease (cGVHD). Univariate analysis revealed that factors affecting OS rate included age (P = 0.022), high risk stage (P = 0.003), AST and TBil elevation before transplantation (P = 0.019 and 0.015 respectively), III-IV hepatic aGVHD (P = 0.000) and HVOD(P = 0.000). Multivariate Cox regression analysis revealed that high risk stage (P = 0.002) and III-IV hepatic aGVHD (P = 0.000) were independent prognostic risk factors affecting both OS rate and TRM rate, while liver dysfunction before transplantation or during conditioning period had no apparent influence on OS rate or TRM rate. CONCLUSION: Allo-HSCT would be administrated for the patients with mild impairment of liver function grade 1 and 2.

Study on Process Parameters of Magnetron Sputtering Titanium Coating in Deep Porous Structures.

In order to improve the energy conversion efficiency and power density of the tritium-powered betavoltaic battery, titanium was deposited on the inner surface of the deep porous three-dimensional structure semiconductor as a tritium absorption material. Therefore, magnetron sputtering technology was used to explore the parameters of titanium coating on the inner surface of a deep porous semiconductor. First, the effects of argon pressure and sputtering power on the properties of titanium films were studied. The properties of the titanium films were characterized by a scanning electron microscope and an atomic force microscope. The optimized sputtering parameters were obtained as follows: argon pressure of 0.5 Pa and sputtering power of 80 W. Based on this parameter, the background vacuum and coating angle were changed, and the titanium film was coated in the deep porous structure. Energy dispersive spectrometry line scan and surface scan were used to analyze the coating results, which showed that these two parameters directly affected the content of titanium in the channel, and the area of titanium in the channel structure accounted for more than 50% under each test condition.

Wireless sensing in high-speed railway turnouts with battery-free materials and devices.

Sustainable energy technologies enable solutions for future green transportation. Realizing status awareness and effective wireless monitoring of rail transit infrastructure in dark environments, narrow spaces, and unattended conditions has always been a challenge. This study presents a battery-free vibration-powered force sensing system (VFSS) that integrates structural loading, sensing, and energy harvesting. The proposed VFSS can sense a switching force of up to 4 kN in the high-speed railway turnout section, deliver 6.9 mW of average power over a broad frequency band (ca. 500 Hz) under a vibration amplitude of 0.2 mm, and realize wireless data transmission. Through a cross-scale design from the device to the system, we demonstrate an all-in-one smart component that features stress flow, signal flow, and energy flow, which could highlight the implementation of energy structures in the future.

Vasorelaxant effects of the extracts and some flavonoids from the buds of Coreopsis tinctoria.

CONTEXT: The buds of Coreopsis tinctoria Nutt (Compositae) are used in the treatment of hypertension in the Uyghur folk medicine in China. OBJECTIVE: To investigate vasorelaxant properties of extracts and some flavonoids from C. tinctoria (CT) and their underlying mechanisms in isolated rat thoracic aortic rings. MATERIALS AND METHODS: Vasorelaxant effects of ethanol extracts of CT (CTA) and its flavonoids as well as water-ethanol eluates from CTA by AB-8 resins (CTAA∼CTAF) were evaluated on rat aortic rings pre-contracted with phenylephrine (PE, 1 µM) or high KCl (60 µM). We evaluated the effect of CTA, CTAD and CTAE on PE-induced contraction in a Ca²âº-free medium and a dose-effect curve of Ca²âº in pre-contracted ring with high KCl. RESULTS: Endothelial removal did not modify the effect of CTAD and CTAE (3.00 g/L) neither on PE-pre-contracted rings (164.78 ± 21.44 and 191.47 ± 16.75%) nor on KCl-pre-contracted rings (75.68 ± 10.76 and 125.14 ± 17.41%) compared with intact-endothelium rings pre-contracted with high KCl (100.49 ± 17.30 and 110.81 ± 16.33%). CTAD and CTAE (3.00 g/L) down-regulated the dose-effect curve of Ca²âº in pre-contraction with high KCl, and inhibited the pre-contraction with PE in a Ca²âº-free medium (p < 0.05). Seven flavonoids were obtained from CTAD, of which luteolin (5) and quercetin (6) were found to be the most effective relaxation in rings precontracted with PE (EC50: 0.006 and 0.039 g/L, p < 0.05) or high KCl (EC50: 0.023 and 0.045 g/L, p < 0.05). DISCUSSION AND CONCLUSION: These data demonstrated the vasorelaxant effect of CT, and its mechanism is likely due to an inhibitory effect on calcium movements through cell membranes.

POGZ suppresses 2C transcriptional program and retrotransposable elements.

The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs). However, the exact mechanisms remain unclear. Here, we show that POGZ plays an important role in the maintenance of ESCs by silencing Dux and endogenous retroviruses (ERVs). POGZ maintains a silent chromatin state at Dux and ERVs by associating with and recruiting TRIM28 and SETDB1, and its loss leads to decreased levels of H3K9me3/H4K20me3, resulting in up-regulation of 2C transcripts and ESC transition to a 2C-like state. POGZ suppresses different classes of ERVs through direct (IAPEy, the intracisternal A-type particle elements) and indirect regulation (MERVL). Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural disease genes such as Serpina3m. Our findings provide important insights into understanding the disease mechanism caused by POGZ dysfunction.

Combination of ST2 With Organ-Specific Biomarker is More Sensitive and Specific for the Diagnosis of Acute Graft-vs-Host Disease.

BACKGROUND: Diagnosis of acute graft-vs-host disease (aGVHD) based on clinical symptoms and biopsy of involved organ was not satisfactory; reliable plasma biomarkers or their panels would be of great value to increase the sensitivity and specificity for such a fatal complication. METHOD: One hundred two patients who received allogeneic hematopoietic stem cell transplantation in our center were included in this study. Systemic biomarkers of ST2, IP10, IL-2Rα, TNFR1, and organ-specific biomarkers of Elafin, REG-3α, and KRT-18F in plasma were tested by ELISA. The correlation of each biomarker or selected panel of some systemic and organ-specific biomarker with aGVHD was investigated. RESULTS: The level of each systemic biomarker in aGVHD patients was significantly higher than that in patients without aGVHD. Organ-specific biomarker of Elafin, REG-3α, and KRT-18F also had predictive value for aGVHD of skin, gastrointestinal tract, and liver, respectively. Combination of ST2 with one of the 3 organ-specific biomarkers could provide more accurate prediction for aGVHD with skin, gastrointestinal tract, and liver, respectively. CONCLUSIONS: All the biomarkers tested in our study correlated with the severity and clinical course of aGVHD. Combination of each systemic biomarker with organ-specific biomarker could increase the sensitivity and specificity for the diagnosis of aGVHD, whereas ST2 with organ-specific biomarker is more sensitive for the diagnosis of organ-specific aGVHD.