Identification of QTN-by-environment interactions and their candidate genes for soybean seed oil-related traits using 3VmrMLM.

Introduction: Although seed oil content and its fatty acid compositions in soybean were affected by environment, QTN-by-environment (QEIs) and gene-by-environment interactions (GEIs) were rarely reported in genome-wide association studies. Methods: The 3VmrMLM method was used to associate the trait phenotypes, measured in five to seven environments, of 286 soybean accessions with 106,013 SNPs for detecting QTNs and QEIs. Results: Seven oil metabolism genes (GmSACPD-A, GmSACPD-B, GmbZIP123, GmSWEET39, GmFATB1A, GmDGAT2D, and GmDGAT1B) around 598 QTNs and one oil metabolism gene GmFATB2B around 54 QEIs were verified in previous studies; 76 candidate genes and 66 candidate GEIs were predicted to be associated with these traits, in which 5 genes around QEIs were verified in other species to participate in oil metabolism, and had differential expression across environments. These genes were found to be related to soybean seed oil content in haplotype analysis. In addition, most candidate GEIs were co-expressed with drought response genes in co-expression network, and three KEGG pathways which respond to drought were enriched under drought stress rather than control condition; six candidate genes were hub genes in the co-expression networks under drought stress. Discussion: The above results indicated that GEIs, together with drought response genes in co-expression network, may respond to drought, and play important roles in regulating seed oil-related traits together with oil metabolism genes. These results provide important information for genetic basis, molecular mechanisms, and soybean breeding for seed oil-related traits.

4D genetic networks reveal the genetic basis of metabolites and seed oil-related traits in 398 soybean RILs.

BACKGROUND: The yield and quality of soybean oil are determined by seed oil-related traits, and metabolites/lipids act as bridges between genes and traits. Although there are many studies on the mode of inheritance of metabolites or traits, studies on multi-dimensional genetic network (MDGN) are limited. RESULTS: In this study, six seed oil-related traits, 59 metabolites, and 107 lipids in 398 recombinant inbred lines, along with their candidate genes and miRNAs, were used to construct an MDGN in soybean. Around 175 quantitative trait loci (QTLs), 36 QTL-by-environment interactions, and 302 metabolic QTL clusters, 70 and 181 candidate genes, including 46 and 70 known homologs, were previously reported to be associated with the traits and metabolites, respectively. Gene regulatory networks were constructed using co-expression, protein-protein interaction, and transcription factor binding site and miRNA target predictions between candidate genes and 26 key miRNAs. Using modern statistical methods, 463 metabolite-lipid, 62 trait-metabolite, and 89 trait-lipid associations were found to be significant. Integrating these associations into the above networks, an MDGN was constructed, and 128 sub-networks were extracted. Among these sub-networks, the gene-trait or gene-metabolite relationships in 38 sub-networks were in agreement with previous studies, e.g., oleic acid (trait)-GmSEI-GmDGAT1a-triacylglycerol (16:0/18:2/18:3), gene and metabolite in each of 64 sub-networks were predicted to be in the same pathway, e.g., oleic acid (trait)-GmPHS-D-glucose, and others were new, e.g., triacylglycerol (16:0/18:1/18:2)-GmbZIP123-GmHD-ZIPIII-10-miR166s-oil content. CONCLUSIONS: This study showed the advantages of MGDN in dissecting the genetic relationships between complex traits and metabolites. Using sub-networks in MGDN, 3D genetic sub-networks including pyruvate/threonine/citric acid revealed genetic relationships between carbohydrates, oil, and protein content, and 4D genetic sub-networks including PLDs revealed the relationships between oil-related traits and phospholipid metabolism likely influenced by the environment. This study will be helpful in soybean quality improvement and molecular biological research.

Strategy and Efficacy of Surgery for Congenital Cervicothoracic Scoliosis with or without Hemivertebra Osteotomy.

OBJECTIVE: Cervicothoracic scoliosis will cause severe deformities in the early stage, and its structure is complex and the surgical methods are varied. The purpose of this research is to explore the indication and analyze the corrective effect of the two different posterior approach surgical strategies, including correction with fusion and hemivertebra osteotomy, for congenital cervicothoracic scoliosis deformities in children and adolescents. METHODS: This was a retrospective study of 21 patients with cervicothoracic scoliosis who received surgical treatment from January 2010 to June 2020, including nine cases of posterior hemivertebra osteotomy and fusion surgery and 12 cases of posterior correction and fusion alone. The Cobb angle, T1 tilt angle, clavicular angle, neck tilt angle, radiographic shoulder height, sagittal vertical axis, coronal balance distance, and local kyphosis angle were measured preoperatively, postoperatively, and at the last follow-up. Posterior approach hemivertebra resection or correction with fusion surgery was adopted based on the different individual characteristics of deformity such as main curve Cobb angle, growth potential, and flexibility. Patients were divided into two groups (osteotomy group and nonosteotomy group) according to whether a hemivertebra osteotomy was performed, and the corrective results in the two groups were compared. Paired-sample t tests or independent-sample t tests were used. RESULTS: The median follow-up after surgery of the 21 patients was 36 months (range, 18-72 months). The Cobb angle was corrected from 45.81° ± 14.23° preoperatively to 10.48° ± 5.56° postoperatively (correction rate, 77.78% ± 8.93%). The T1 tilt angle decreased from 15.26° ± 7.08° preoperatively to 3.33° ± 2.14° postoperatively (correction rate,73.42% ± 21.86%). The radiographic shoulder height was corrected from 1.13 ± 0.74 cm preoperatively to 0.52 ± 0.42 cm postoperatively (correction rate, 39.51% ± 35.65%). The clavicular angle improved from 2.52° ± 1.55° preoperatively to 1.16° ± 0.96° postoperatively (correction rate, 47.18% ± 35.84%). No significant differences were found at the last follow-up (p > 0.05). The Cobb angle of the main curve, T1 tilt angle, clavicular angle, cervical tilt angle, and shoulder height difference were similar in the two groups (p > 0.05). CONCLUSIONS: Posterior approach hemivertebra resection or correction with fusion surgery can be used in the treatment of congenital cervicothoracic scoliosis with satisfactory results, and the surgeon can make an individualized surgical plan according to individual characteristics of deformity.

Domestication and improvement genes reveal the differences of seed size- and oil-related traits in soybean domestication and improvement.

To address domestication and improvement studies of soybean seed size- and oil-related traits, a series of domesticated and improved regions, loci, and candidate genes were identified in 286 soybean accessions using domestication and improvement analyses, genome-wide association studies, quantitative trait locus (QTL) mapping and bulked segregant analyses in this study. As a result, 534 candidate domestication regions (CDRs) and 458 candidate improvement regions (CIRs) were identified in this study and integrated with those in five and three previous studies, respectively, to obtain 952 CDRs and 538 CIRs; 1469 loci for soybean seed size- and oil-related traits were identified in this study and integrated with those in Soybase to obtain 433 QTL clusters. The two results were intersected to obtain 245 domestication and 221 improvement loci for the above traits. Around these trait-related domestication and improvement loci, 7 domestication and 7 improvement genes were found to be truly associated with these traits, and 372 candidate domestication and 87 candidate improvement genes were identified using gene expression, SNP variants in genome, miRNA binding, KEGG pathway, DNA methylation, and haplotype analysis. These genes were used to explain the trait changes in domestication and improvement. As a result, the trait changes can be explained by their frequencies of elite haplotypes, base mutations in coding region, and three factors affecting their expression levels. In addition, 56 domestication and 15 improvement genes may be valuable for future soybean breeding. This study can provide useful gene resources for future soybean breeding and molecular biology research.

A combinatorial strategy to identify various types of QTLs for quantitative traits using extreme phenotype individuals in an F2 population.

Theoretical and applied studies demonstrate the difficulty of detecting extremely over-dominant and small-effect genes for quantitative traits via bulked segregant analysis (BSA) in an F2 population. To address this issue, we proposed an integrated strategy for mapping various types of quantitative trait loci (QTLs) for quantitative traits via a combination of BSA and whole-genome sequencing. In this strategy, the numbers of read counts of marker alleles in two extreme pools were used to predict the numbers of read counts of marker genotypes. These observed and predicted numbers were used to construct a new statistic, Gw, for detecting quantitative trait genes (QTGs), and the method was named dQTG-seq1. This method was significantly better than existing BSA methods. If the goal was to identify extremely over-dominant and small-effect genes, another reserved DNA/RNA sample from each extreme phenotype F2 plant was sequenced, and the observed numbers of marker alleles and genotypes were used to calculate Gw to detect QTGs; this method was named dQTG-seq2. In simulated and real rice dataset analyses, dQTG-seq2 could identify many more extremely over-dominant and small-effect genes than BSA and QTL mapping methods. dQTG-seq2 may be extended to other heterogeneous mapping populations. The significance threshold of Gw in this study was determined by permutation experiments. In addition, a handbook for the R software dQTG.seq, which is available at https://cran.r-project.org/web/packages/dQTG.seq/index.html, has been provided in the supplemental materials for the users' convenience. This study provides a new strategy for identifying all types of QTLs for quantitative traits in an F2 population.

Expression of Cyclin D1 gene in ovarian cancer and effect of silencing its expression on ovarian cancer cells based on the Oncomine database.

We aimed to analyze the expression of Cyclin D1 (CCND1) gene in ovarian cancer and the influence of silencing its expression on ovarian cancer cells based on the Oncomine database. The expression of CCND1 gene in ovarian cancer was analyzed by utilizing the relevant information in different tumors and Oncomine database. The correlation between CCDN1 expression level and prognosis of ovarian cancer was analyzed by the online database Kaplan-Meier (kmplot.com). The expression of CCND1 gene in ovarian cancer and the effect of silencing its expression on cancer cells were analyzed by cell experiments. After mining and comprehensively analyzing 7 studies on the differential expression of CCND1 gene in ovarian cancer tissue and normal ovarian tissue included in the Oncomine database, it was found that the median value of CCND1 gene ranked 218.0 (P = 8.03 × 10-6) among all differentially expressed genes, suggesting that CCND1 gene expression in ovarian cancer tissue was higher than that in normal ovarian tissue. Adib Ovarian, Bonome Ovarian and Hendrix Ovarian microarrays revealed that the expression of CCND1 gene in ovarian cancer tissue was significantly higher than that in normal ovarian tissue (P < 0.05). Kaplan-Meier Plotter database showed that the overall survival and progression-free survival of ovarian cancer patients with high CCND1 expression were significantly shorter than those of patients with low CCND1 expression (P < 0.05). The expression levels of CCND1 gene in normal ovarian epithelial cells and SKOV3 ovarian cancer cells were detected by RT-PCR. The expression of CCND1 gene was significantly higher in SKOV3 group than that in control group (P < 0.01). Flow cytometry revealed that the percentage of cells in G0/G1 phase was significantly higher, while that in S phase was lower in SKOV3 + siCCND1 group than the values of SKOV3 and SKOV3 + siNC groups (P < 0.05). The apoptosis rate of ovarian cancer cells was significantly higher in SKOV3 + siCCND1 group than those of SKOV3 and SKOV3 + siNC groups (P < 0.01). CCND1 gene is highly expressed in ovarian cancer tissue and related to prognosis. Preoperative evaluation of CCND1 gene expression in ovarian cancer patients may benefit the assessment of risk and prognosis.

Deformed Complex Vertebral Osteotomy Technique for Management of Severe Congenital Spinal Angular Kyphotic Deformity.

OBJECTIVES: To (i) introduce the deformed complex vertebral osteotomy (DCVO) technique for the treatment of severe congenital angular spinal kyphosis; (ii) evaluate the sagittal correction efficacy of the DCVO technique; and (iii) discuss the advantages and limitations of the DCVO technique. METHODS: Multiple malformed vertebrae were considered a malformed complex, and large-range and angle wedge osteotomy was performed within the complex using the DCVO technique. Patients with local kyphosis greater than 80° who were treated with DCVO and did not have tumors, infections, or a history of surgery were included. A retrospective case study was performed in these patients with severe angular kyphosis who underwent the DCVO technique from 2008 to 2016. Demographic data, the operating time, and the volume of intraoperative blood loss were collected. Spinopelvic parameters (pelvic incidence [PI], pelvic tilt [PT], and sacral slope [SS]), local and global sagittal parameters (deformity angle, thoracic kyphosis [TK], and lumbar lordosis [LL]), visual analog scale (VAS) score, and Oswestry disability index (ODI) score were recorded pre- and postoperatively. Paired t-tests (α = 0.05) were used for all data (to compare the mean preoperative value with the mean postoperative and most recent follow-up values). P < 0.05 was considered statistically significant. RESULTS: Twenty-nine patients with a mean age of 34 years (range, 15-55) were included in the final analysis. Seventeen patients were male, and 12 were female. The mean follow-up was 44 months (range, 26-62). The mean operating time was 299 min (range, 260-320 min). The mean blood loss was 2110 mL (range, 1500-2900 mL). Three patients had T7 -T8 deformities (3/29, 10.3%), six had T8 -T9 deformities (6/29, 20.7%), six had T9 -T10 deformities (6/29, 20.7%), 10 had T10 -T11 deformities (10/29, 34.5%), three had T11 -T12 deformities (3/29, 10.3%), and one had T9 -T11 deformities (1/29, 3.4%). The mean local deformity angle significantly improved from 94.9° ± 10.8° to 24.0° ± 2.3° through the DCVO technique, with no significant loss at the follow-up. Moreover, the global sagittal parameters and spinopelvic parameters exhibited ideal magnitudes of improvement; TK decreased from 86.1° ± 12.1° to 28.7° ± 2.5°, LL improved from 94.5° ± 4.1° to 46.1° ± 3.0°, and PI minus LL improved from -60.9° ± 6.5° to -13.7° ± 2.6°. Both the VAS and ODI scores significantly improved at the last follow-up. CSF fistula and neural injury did not occur during the perioperative period. At the last follow-up, fixation failure was not observed. CONCLUSION: The DCVO technique provides an alternative and effective method for the treatment of congenital severe angular spinal kyphotic deformities and may decrease the occurrence of perioperative complications.

Epidemiological and clinical characteristics of 65 hospitalized patients with COVID-19 in Liaoning, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly to multiple countries through its infectious agent severe acute respiratory syndrome coronavirus 2. The severity, atypical clinical presentation, and lack of specific anti-viral treatments have posed a challenge for the diagnosis and treatment of COVID-19. Understanding the epidemiological and clinical characteristics of COVID-19 cases in different geographical areas is essential to improve the prognosis of COVID-19 patients and slow the spread of the disease. AIM: To investigate the epidemiological and clinical characteristics and main therapeutic strategy for confirmed COVID-19 patients hospitalized in Liaoning Province, China. METHODS: Adult patients (n = 65) with confirmed COVID-19 were enrolled in this retrospective study from January 20 to February 29, 2020 in Liaoning Province, China. Pharyngeal swabs and sputum specimens were collected from the patients for the detection of severe acute respiratory syndrome coronavirus 2 nucleic acid. Patient demographic information and clinical data were collected from the medical records. Based on the severity of COVID-19, the patients were divided into nonsevere and severe groups. All patients were followed until March 20, 2020. RESULTS: The mean age of 65 COVID-19 patients was 45.5 ± 14.4 years, 56.9% were men, and 24.6% were severe cases. During the 14 d before symptom onset, 25 (38.5%) patients lived or stayed in Wuhan, whereas 8 (12.3%) had no clear history of exposure. Twenty-nine (44.6%) patients had at least one comorbidity; hypertension and diabetes were the most common comorbidities. Compared with nonsevere patients, severe patients had significantly lower lymphocyte counts [median value 1.3 × 109/L (interquartile range 0.9-1.95) vs 0.82 × 109/L (0.44-1.08), P < 0.001], elevated levels of lactate dehydrogenase [450 U/L (386-476) vs 707 U/L (592-980), P < 0.001] and C-reactive protein [6.1 mg/L (1.5-7.2) vs 52 mg/L (12.7-100.8), P < 0.001], and a prolonged median duration of viral shedding [19.5 d (16-21) vs 23.5 d (19.6-30.3), P = 0.001]. The overall median viral shedding time was 19.5 d, and the longest was 53 d. Severe patients were more frequently treated with lopinavir/ritonavir, antibiotics, glucocorticoid therapy, immunoglobulin, thymosin, and oxygen support. All patients were discharged following treatment in quarantine. CONCLUSION: Our findings may facilitate the identification of severe cases and inform clinical treatment and quarantine decisions regarding COVID-19.

Epidemiological and clinical characteristics of fifty-six cases of COVID-19 in Liaoning Province, China.

BACKGROUND: Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of ß-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM: To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS: The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS: The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION: SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

An evolutionary population structure model reveals pleiotropic effects of GmPDAT for traits related to seed size and oil content in soybean.

Seed oil traits in soybean that are of benefit to human nutrition and health have been selected for during crop domestication. However, these domesticated traits have significant differences across various evolutionary types. In this study, we found that the integration of evolutionary population structure (evolutionary types) with genome-wide association studies increased the power of gene detection, and it identified one locus for traits related to seed size and oil content on chromosome 13. This domestication locus, together with another one in a 200-kb region, was confirmed by the GEMMA and EMMAX software. The candidate gene, GmPDAT, had higher expressional levels in high-oil and large-seed accessions than in low-oil and small-seed accessions. Overexpression lines had increased seed size and oil content, whereas RNAi lines had decreased seed size and oil content. The molecular mechanism of GmPDAT was deduced based on results from linkage analysis for triacylglycerols and on histocytological comparisons of transgenic soybean seeds. Our results illustrate a new approach for identifying domestication genes with pleiotropic effects.

A SAM-I riboswitch with the ability to sense and respond to uncharged initiator tRNA.

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.

Identification of a modori-inducing proteinase in the threadfin bream: Molecular cloning, tissue distribution and proteinase leakage from viscera during ice storage.

Previously we purified and characterized a sarcoplasmic serine proteinase (SSP) from the belly muscle of the threadfin bream as a modori-inducing proteinase. In our attempt to clarify the structure and physiological functions of SSP, we successfully cloned the full-length cDNA of SSP (ORF 726 bp). The deduced amino acid sequence of SSP (241 residues) was highly homologous to fish trypsinogen. The distribution of SSP mRNA and the proteinase activity in the tissue indicated that SSP was mainly synthesized and existed in the digestive system under physiological conditions. After ice storage of the threadfin bream without gutting, a high SSP activity was detected only in the belly muscle because of SSP leaked from the viscera. Therefore, it is desirable to use edible proteinase inhibitor to inactivate the leaked SSP during production of surimi-based products or to take effective measures to prevent the proteinase leakage during post-harvest storage.

Three-dimensional genetic networks among seed oil-related traits, metabolites and genes reveal the genetic foundations of oil synthesis in soybean.

Although the biochemical and genetic basis of lipid metabolism is clear in Arabidopsis, there is limited information concerning the relevant genes in Glycine max (soybean). To address this issue, we constructed three-dimensional genetic networks using six seed oil-related traits, 52 lipid metabolism-related metabolites and 54 294 SNPs in 286 soybean accessions in total. As a result, 284 and 279 candidate genes were found to be significantly associated with seed oil-related traits and metabolites by phenotypic and metabolic genome-wide association studies and multi-omics analyses, respectively. Using minimax concave penalty (MCP) and smoothly clipped absolute deviation (SCAD) analyses, six seed oil-related traits were found to be significantly related to 31 metabolites. Among the above candidate genes, 36 genes were found to be associated with oil synthesis (27 genes), amino acid synthesis (four genes) and the tricarboxylic acid (TCA) cycle (five genes), and four genes (GmFATB1a, GmPDAT, GmPLDα1 and GmDAGAT1) are already known to be related to oil synthesis. Using this information, 133 three-dimensional genetic networks were constructed, 24 of which are known, e.g. pyruvate-GmPDAT-GmFATA2-oil content. Using these networks, GmPDAT, GmAGT and GmACP4 reveal the genetic relationships between pyruvate and the three major nutrients, and GmPDAT, GmZF351 and GmPgs1 reveal the genetic relationships between amino acids and seed oil content. In addition, GmCds1, along with average temperature in July and the rainfall from June to September, influence seed oil content across years. This study provides a new approach for the construction of three-dimensional genetic networks and reveals new information for soybean seed oil improvement and the identification of gene function.

Ulinastatin ameliorates acute kidney injury induced by crush syndrome inflammation by modulating Th17/Treg cells.

BACKGROUND: Acute kidney injury (AKI) is the main complication of crush syndrome (CS), and it is also a cause of lethality in CS. However, effective treatments for AKI are still lacking. Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor extracted from human urine that reportedly modulates innate immunity and pro-inflammatory responses in sepsis. Here, we explored the effect and the potential mechanism of ulinastatin on crush syndrome-induced acute kidney injury (CSAKI). METHODS: A CSAKI rat model was established by using a digital crush injury device platform. Forty-six male Wistar rats were randomly divided into five groups: the normal control (n = 6), CSAKI model (n = 10), CSAKI plus UTI1 (50,000 U/kg) (n = 10), CSAKI plus UTI2 (100,000 U/kg) (n = 10) and CSAKI plus UTI3 (200,000 U/kg) (n = 10) groups. Hematoxylin-eosin (HE) staining was used to investigate the reliability of the CSAKI model. The percentage of Th17/Treg lymphocytes in peripheral blood was measured by flow cytometry, and the expression of transcription factors associated with Th17/Treg cells was evaluated by quantitative real-time polymerase chain reaction (PCR). In addition, specific cytokines released by Th17/Treg cells in serum and kidney tissues were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with ulinastatin could significantly decrease serum BUN, CK, Scr, Mb and K+ levels compared with CSAKI group. HE staining results showed that ulinastatin could inhibit inflammatory cells infiltration, decrease sarcomere rupture in muscle tissues induced by extrusion, and alleviate the glomerular congestion and edema, as well as decrease myoglobin cast in kidney tissues. The proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells and Foxp3 expression levels were decreased in the CSAKI animals, while IL-17 expression levels were significantly increased, compared with those of the normal control group. Treatment with ulinastatin upregulated the proportion of Treg cells in CD4+ T cells and downregulated the expression of IL-17 compared with those of the CSAKI group. CONCLUSION: The findings of our study indicate that UTI attenuates CS-induced AKI and alleviate the inflammatory response during the early stage. The mechanism of UTI may be due to regulating the balance between Th17/Treg cells. Our study provides a new mechanism for the beneficial effect of ulinastatin on CSAKI.

Purification and characterization of a sarcoplasmic serine proteinase from threadfin bream Nemipterus virgatus muscle.

A sarcoplasmic serine proteinase (SSP) was purified from threadfin bream (Nemipterus virgatus) belly muscle by ammonium sulfate precipitation and a series of chromatographies including Q-Sepharose, Phenyl Sepharose and Superdex 200. The SSP was purified 1967 folds with a yield of 4.8%. The molecular weight of the SSP was estimated to be 43.5 kDa and 22.5 kDa on SDS-PAGE under non-reducing and reducing conditions, respectively. The N-terminal amino acid sequence of the two protein bands were determined as IVGGYEXQPYSQAHQVSLNSGY and corresponded. It is suggested that the SSP exists as a homodimer. Optimum pH and temperature were 9.5 and 50 °C, using Boc-Val-Pro-Arg-MCA as a substrate. Substrate specificity and effects of inhibitors indicated that the SSP was a trypsin-like serine proteinase. The SSP was responsible for hydrolyzing myosin heavy chain (MHC) and inducing modori phenomenon in the threadfin bream surimi gel. Thus, the SSP was considered as a modori-inducing proteinase.

Bradyrhizobium diazoefficiens USDA 110- Glycine max Interactome Provides Candidate Proteins Associated with Symbiosis.

Although the legume-rhizobium symbiosis is a most-important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog- and domain-based approaches, we constructed an interspecies protein interactome containing 5115 protein-protein interactions between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was further validated by the expression pattern analysis in nodules, gene ontology term semantic similarity, co-expression analysis, and luciferase complementation image assay. In the G. max-B. diazoefficiens interactome, bacterial proteins are mainly ion channel and transporters of carbohydrates and cations, while G. max proteins are mainly involved in the processes of metabolism, signal transduction, and transport. We also identified the top 10 highly interacting proteins (hubs) for each species. Kyoto Encyclopedia of Genes and Genomes pathway analysis for each hub showed that a pair of 14-3-3 proteins (SGF14g and SGF14k) and 5 heat shock proteins in G. max are possibly involved in symbiosis, and 10 hubs in B. diazoefficiens may be important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis-related soluble N-ethylmaleimide sensitive factor attachment protein receptor proteins may play roles in regulating bacterial ion channels, and SGF14g and SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The predicted interactome provide a valuable basis for understanding the molecular mechanism of nodulation in soybean.

Epigenetic alterations contribute to promoter activity of imprinting gene IGF2.

The expression of insulin-like growth factor 2 (IGF2), a classical imprinting gene, didn't completely correlate with its imprinting profiles in hepatocellular carcinoma (HCC). The mechanistic importance of promoter activity in regulation of IGF2 has not been fully clarified. Here we show that histone 3 lysine 4 trimethylation (H3K4me3) modified by menin-MLL complex of IGF2 promoter contributes to promoter activity of IGF2. The strong binding of menin and abundant H3K4me3 at the DNA demethylated P3/4 promoters were observed in Hep3B cells with the robust expression of IGF2. In IGF2-low-expressing HepG2 cells, menin didn't bind to DNA hypermethylated P3/4 regions; however, menin overexpression inhibited DNA methylation and promoted H3K4me3 at the P3/4 as well as IGF2 expression in HepG2. In addition, the H3K4me3 at P3/4 locus was activated in primary HCC specimens with high IGF2 expression. Furthermore, inhibition of the menin/MLL interaction via MI-2/3 reduced IGF2 expression, inhibited the IGF1R-AKT pathway, and significantly repressed HCC with robust expression of IGF2. Taken together, we conclude that H3K4me3 of P3/4 locus mediated by the menin-MLL complex is a novel epigenetic mechanism for releasing IGF2.

Disaster Medicine in China: Present and Future.

Disaster can strike people in any community at any time anywhere in the world. Disasters occur with high frequency, take on multiple forms, and exert wide influence, typically causing property damage, injuries, and death. As the world's largest developing country, China incurs great costs when a disaster hits. After the Wenchuan earthquake in 2008, the Chinese government focused its attention on the construction of an emergency response system, the creation of disaster prevention and mitigation systems, and the development of a disaster medicine program. Here, we describe the current status of disaster medicine in China, focusing on the following four aspects: the Emergency Management System, Education & Training, Rescue Practices, and Research. We also discuss the future of disaster medicine in China. (Disaster Med Public Health Preparedness. 2018;12:157-165).

Sacroiliac joint tuberculosis: surgical management by posterior open-window focal debridement and joint fusion.

BACKGROUND: Sacroiliac joint tuberculosis(SJT) is relatively uncommon, but it may cause severe sacroiliac joint destruction and functional disorder. Few studies in the literature have been presented on SJT, reports of surgical treatment for SJT are even fewer. In this study, we retrospectively reviewed surgical management of patients with severe SJT of 3 different types and proposed to reveal the clinical manifestations and features and aim to determine the efficiency and security of such surgical treatment. METHODS: We reviewed 17 patients with severe SJT of 3 different types who underwent posterior open-window focal debridement and bone graft for joint fusion. Among them,five patients with anterior sacral abscess had anterior abscess curettage before debridement. Two patients with lumbar vertebral tuberculosis received one-stage posterior tuberculous debridement, interbody fusion and instrumentation. Follow-up was performed 36 months (26 to 45 months) using the following parameters: erythrocyte sedimentation rate(ESR), status of joint bony fusion on CT scan, visual analogue scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: Buttock pain and low back pain were progressively relieved with time. 6 months later, pain was not obvious, and ESR resumed to normal levels within 3 months. Solid fusion of the sacroiliac joint occurred within 12 months in all cases. No complications or recurrence occurred. At final follow-up, all patients had no pain or only minimal discomfort over the affected joint and almost complete functional recovery. CONCLUSIONS: Posterior open-window focal debridement and joint fusion is an efficient and secure surgical method to treat severe SJT. If there is an abscess in the front of the sacroiliac joint, anterior abscess curettage should be performed as a supplement.