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Background The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers. Methods tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines. Results A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs’ expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines. Conclusion These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery.

Background Renal calyx diverticulum refers to a cystic lesion covered with the transitional epithelium in the renal parenchyma. Although there is no clear evidence that calyx diverticulum can cause hypertension, there exists a close association between the two, and there are few related reports. Herein, we reported the case of a child with renal calyx diverticulum complicated with hypertension and summarized the diagnosis and treatment. Case presentation Physical examination of the patient, an 11-year-old child, revealed a left renal cyst with hypertension (155/116 mmHg). There were no related symptoms. Routine urine and blood biochemical examinations showed no abnormalities. Imaging revealed left renal cyst compression causing the hypertension. She underwent renal cyst fluid aspiration and injection of a sclerosing agent into the capsule, but her blood pressure increased again 3 days postoperatively. Color Doppler ultrasonography showed that the size of the left renal cyst was the same as that preoperatively. To further confirm the diagnosis, cystoscopic retrograde ureteropyelography was performed to confirm the diagnosis of renal calyx diverticulum. Subsequently, renal calyceal diverticulum resection and calyx neck enlargement were performed. The operation went smoothly and the blood pressure returned to normal postoperatively. No abnormalities were noted at the 7-month postoperative follow-up. Conclusion There exists an association between renal calyx diverticulum and hypertension. Therefore, hypertension can be considered a surgical indication for renal calyx diverticulum. Moreover, renal calyceal diverticulum in children can be easily misdiagnosed as a renal cyst. Therefore, it is important to be vigilant to prevent a series of complications, such as postoperative urine leakage, in such cases.

Background The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples. Methods Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS. Results In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged interaction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04–1.63). The interaction of smoking with age was also replicated. Conclusions Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged

Background Overseas imported dengue fever is an important factor in local outbreaks of this disease in the mainland of China. To better prevent and control such local outbreaks, the epidemiological characteristics and temporal-spatial distribution of overseas imported dengue fever cases in provincial-level administrative divisions (PLADs) where dengue fever is outbreak in the mainland of China were explored. Methods Using the Chinese National Notifiable Infectious Disease Reporting Information System (CNNDS), we identified overseas imported dengue fever cases in dengue fever outbreak areas in the mainland of China from 2005 to 2019 to draw the epidemic curve and population characteristic distribution of overseas imported cases in each PLAD. Based on spatial autocorrelation analysis of ArcGIS 10.5 and temporal-spatial scanning analysis of SaTScan 9.5, we analyzed the temporal-spatial distribution of overseas imported dengue fever in dengue fever outbreak areas in the mainland of China. Results A total of 11,407 imported cases, mainly from Southeast Asia, were recorded from 2005 to 2019 in these 13 PLADs. Of which 62.1% were imported into Yunnan and Guangdong Provinces. Among the imported cases, there were more males than females, mainly from the 21–50 age group. The hot spots were concentrated in parts of Yunnan, Guangdong and Fujian Provinces. We found the cluster of infected areas were expanding northward. Conclusions Based on the analysis of overseas imported dengue cases in 13 PLADs of the mainland of China from 2005 to 2019, we obtained the epidemiological characteristics and spatial distribution of imported dengue cases. Border controls need to pay attention to key population sectors, such as 21–50 years old men and education of key populations on dengue prevention. There is a need to improve the awareness of the prevention and control of imported cases in border areas. At the same time, northern regions cannot relax their vigilance. Graphical Abstract

Background Kuruma shrimp, a major commercial shrimp species in the world, has two cryptic or sibling species, Marsupenaeus japonicus and Marsupenaeus pulchricaudatus. Codon usage analysis would contribute to our understanding of the genetic and evolutionary characteristics of the two Marsupenaeus species. In this study, we analyzed codon usage and related indices using coding sequences (CDSs) from RNA-seq data. Results Using CodonW 1.4.2 software, we performed the codon bias analysis of transcriptomes obtained from hepatopancreas tissues, which indicated weak codon bias. Almost all parameters had similar correlations for both species. The gene expression level (FPKM) was negatively correlated with A/T3s. We determined 12 and 14 optimal codons for M. japonicus and M. pulchricaudatus, respectively, and all optimal codons have a C/G-ending. The two Marsupenaeus species had different usage frequencies of codon pairs, which contributed to further analysis of transcriptional differences between them. Orthologous genes that underwent positive selection (ω > 1) had a higher correlation coefficient than that of experienced purifying selection (ω Conclusions This study provides a relatively comprehensive understanding of the correlations among codon usage bias, gene expression, and selection pressures of CDSs for M. japonicus and M. pulchricaudatus. The genetic evolution was driven by mutations and selection pressure. Moreover, the results point out new insights into the specificities and evolutionary characteristics of the two Marsupenaeus species.

Background This study hoped to explore the potential biomarkers and associated metabolites during osteosarcoma (OS) progression based on bioinformatics integrated analysis. Methods Gene expression profiles of GSE28424, including 19 human OS cell lines (OS group) and 4 human normal long bone tissue samples (control group), were downloaded. The differentially expressed genes (DEGs) in OS vs. control were investigated. The enrichment investigation was performed based on DEGs, followed by protein–protein interaction network analysis. Then, the feature genes associated with OS were explored, followed by survival analysis to reveal prognostic genes. The qRT-PCR assay was performed to test the expression of these genes. Finally, the OS-associated metabolites and disease-metabolic network were further investigated. Results Totally, 357 DEGs were revealed between the OS vs. control groups. These DEGs, such as CXCL12, were mainly involved in functions like leukocyte migration. Then, totally, 38 feature genes were explored, of which 8 genes showed significant associations with the survival of patients. High expression of CXCL12, CEBPA, SPARCL1, CAT, TUBA1A, and ALDH1A1 was associated with longer survival time, while high expression of CFLAR and STC2 was associated with poor survival. Finally, a disease-metabolic network was constructed with 25 nodes including two disease-associated metabolites cyclophosphamide and bisphenol A (BPA). BPA showed interactions with multiple prognosis-related genes, such as CXCL12 and STC2. Conclusion We identified 8 prognosis-related genes in OS. CXCL12 might participate in OS progression via leukocyte migration function. BPA might be an important metabolite interacting with multiple prognosis-related genes.

Background Chinese soft-shell turtle (Pelodiscus sinensis) is an important commercial species for their high nutritional value and unique taste, but it has been a vulnerable species due to habitat loss. In this study, homologous juvenile turtles were allocated to lake, pond and paddy field to investigate the habitat effects on turtles. Results The growth, morphology and gut microbial communities were monitored during the 4 months cultural period. It showed higher growth rate of turtles in paddy field and pond. The appearance, visceral coefficients, gut morphology and microbial communities in turtles were distinct among different habitats. The microbial community richness on Chao1 was obviously lower in initial turtle guts from greenhouses, whereas it was relative higher in turtle guts sampled from paddy fields than ponds and lake. Significant differences on dominant microbes were found among initial and subsequent samples from different habitats. Firmicutes was the most abundant phylum in the guts of turtles sampled from the greenhouse initially, while Proteobacteria was the most abundant phylum after cultivation in different habitats, followed by Bacteroidetes. The microbial composition were distinct in different habitats at 60d, and the appearance of dominant phyla and genera was more driven by sampling time than habitats at 120d. Both the sampling time and habitats affected the appearance of dominant phyla and genera during the cultivation. The functional predictions indicated that both habitat type and sampling time had significant effects on metabolic pathways, especially amino acid and carbohydrate metabolism. Conclusions The turtles could adapt to natural lakes, artificial ponds and paddy fields. The gut microbial abundance was different among the habitats and sampling time. The species of microbes were significantly more diverse in paddy field specimens than in those from ponds and lakes. Rice-turtle coculture is a potential ecological and economic farming mode that plays important roles in wild turtle protection and food security.

Background The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis. Methods Azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software. Results Persistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified. Conclusion These findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation. Graphical abstract

Background Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients’ treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. Methods Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. Results Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. Conclusions This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

Background Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. Results To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells. Conclusions A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.

Background In orthopedic application, stress-shielding effects of implant materials cause bone loss, which often induces porosis, delayed bone healing, and other complications. We aimed to compare the stress-shielding effects of locked compression plate (LCP) and limited-contact dynamic compression plate (LC-DCP) in dogs with plate-fixed femurs. Methods Bilateral intact femurs of 24 adult dogs were fixed by adult forearm 9-hole titanium plates using minimally invasive plate osteosynthesis (MIPPO) technology, with LCP on the left and LC-DCP on the right femurs. Dogs were sacrificed at 6 weeks, 12 weeks, and 24 weeks after surgery, and bone specimens were used to evaluate the efficacies of different fixing methods on bones through X-ray, dual-energy X-ray absorptiometry (DEXA), histology, MicroCT, and biomechanics analyses. Results X-ray results showed significant callus formation and periosteal reaction in the LC-DCP group. Bone cell morphology, degree of osteoporosis, and bone mineral density (BMD) changes of the LCP group were significantly better than that of the LC-DCP group. MicroCT results showed that the LCP group had significantly reduced degree of cortical bone osteoporosis than the LC-DCP group. Tissue mineral density (TMD) in the LCP group was higher than that in the LC-DCP group at different time points (6 weeks, 12 weeks, and 24 weeks). Biomechanics analyses demonstrated that the compressive strength and flexural strength of bones fixed by LCP were better than that by LC-DCP. Conclusions Stress-shielding effects of LCP are significantly weaker than that of LC-DCP, which is beneficial to new bone formation and fracture healing, and LCP can be widely used in clinic for fracture fixation.

Background Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer and has one of the highest mortality rates. An increasing number of long non-coding RNAs (LncRNAs) were reported to be associated with the occurrence and progression of LADC. Thus, it is necessary and reasonable to find new prognostic biomarkers for LADC among LncRNAs. Methods Differential expression analysis, survival analysis, PCR experiments and clinical feature analysis were performed to screen out the LncRNA which was significantly related to LADC. Its role in LADC was verified by CCK-8 assay and colony. Furthermore, competing endogenous RNA (ceRNA) regulatory network construction, enrichment analysis and protein–protein interaction (PPI) network construction were performed to investigate the downstream regulatory network of the selected LncRNA. Results A total of 2431 differentially expressed LncRNAs (DELncRNAs) and 2227 differentially expressed mRNAs (DEmRNAs) were from The Cancer Genome Atlas database. Survival analysis results indicated that lnc-YARS2-5, lnc-NPR3-2 and LINC02310 were significantly related to overall survival. Their overexpression indicated poor prognostic. PCR experiments and clinical feature analysis suggested that LINC02310 was significantly correlated with TNM-stage and T-stage. CCK-8 assay and colony formation assay demonstrated that LINC02310 acted as an enhancer in LADC. In addition, 3 targeted miRNAs of LINC02310 and 414 downstream DEmRNAs were predicted. The downstream DEmRNAs were then enriched in 405 Gene Ontology terms and 11 Kyoto Encyclopedia of Genes and Genomes pathways, which revealed their potential functions and mechanisms. The PPI network showed the interactions among the downstream DEmRNAs. Conclusions This study verified LINC02310 as an enhancer in LADC and performed comprehensive analyses on its downstream regulatory network, which might benefit LADC prognoses and therapies.

Background and aim Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. Methods This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight Results Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1–24 ml/(kg · day), 139 (14.4%) received 25–49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P P Conclusions A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. Trial registration ClinicalTrials.gov Identifier: NCT03453502. Registration date: March 5, 2018. This study was retrospectively registered.

Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.

Background Recent studies indicated that exosomal programmed death-ligand 1 (PD-L1) derived from cancers could induce immunosuppression and tumor pathogenesis. However, it is unclear how exosomes influence osteosarcoma (OS) progression and whether PD-L1 also exists in serum exosomes (Sr-exosomes) of patients with osteosarcoma. We examined serum exosomes from 70 OS patients, 9 patients with benign tumors and 22 healthy donors. OS-derived exosomes were functionally evaluated in vivo and in vitro. Results The characteristics of exosomes derived from OS patient serum and OS cell lines were confirmed by several methods. We found OS patients had a higher level of exosomal PD-L1 compared to healthy donors. Meanwhile, OS patients with pulmonary metastasis also showed a relatively higher level of exosomal PD-L1 than patients without metastasis. Next, bioinformatic analysis demonstrated that Sr-exosomes isolated from OS patients may involve in the important process of immune function and cancer pathogenesis for OS patients. Co-expression network centered with PD-L1 among Sr-exosomal differently expressed mRNA demonstrated exosomal N-cadherin had a close relationship with exosomal PD-L1 expression. Then, we confirmed higher level of Sr-exosomal N-cadherin in OS patients with pulmonary metastasis compared to ones without metastasis. Furthermore, we elucidated osteosarcoma-derived exosomes and exosomal-PD-L1 promoted the pulmonary metastasis in metastatic models. ROC (Receiver Operating Characteristic Curve) analysis showed AUC (Area Under Curve) of 0.823 for exosomal PD-L1, 0.806 for exosomal N-cadherin and 0.817 for exosomal N-cadherin/E-cadherin to distinguish OS patients with pulmonary metastasis from ones without metastasis. Conclusions Osteosarcoma stimulates pulmonary metastasis by releasing exosomes, that carry PD-L1 and N-cadherin. Detection of exosomal PD-L1 and N-cadherin from serum of OS patients may predict pulmonary metastasis progression for OS patients.

Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. Results This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

Rationale Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been described as potential predictor of poor outcome for COVID-19, without considering its time-varying behavior though. Methods Prognostic value of SpO2/FiO2 was evaluated by jointly modeling the longitudinal responses of SpO2/FiO2 and time-to-event data retrieved from 280 severe and critically ill (intensive care) patients with COVID-19. Results A sharply decrease of SpO2/FiO2 from the first to second measurement for non-survivors was observed, and a strong association between square root SpO2/FiO2 and mortality risk was demonstrated, with a unit decrease in the marker corresponding to 1.82-fold increase in mortality risk (95% CI: 1.56–2.13). Conclusions The current study suggested that SpO2/FiO2 could serve as a non-invasive prognostic marker to facilitate early adjustment for treatment, thus improving overall survival.

Background Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear. Methods RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts. Results In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression. Conclusion Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.

Background Previous research has documented mental health status among rural-to-urban migrant children (labeled as “migrant children” henceforth) and urban children. However, the findings remain unclear. In addition, far less attention has been paid to rural children’s psychological outcomes. The purpose of this study was to compare mental health status among migrant, urban and rural school-age children in Guangdong Province, China. Methods This was a cross-sectional study involving 372 migrant, 254 urban and 268 rural children selected respectively from 3 private schools, 4 public schools and 2 village schools in Guangdong Province, China. Participants provided their socio-demographic information and completed the Strengths and Difficulties Questionnaire (SDQ) to assess mental health. One-way analyses of variance (ANOVAs) and Bonferroni post hoc test were used to evaluate SDQ scores differences. A multiple linear regression analysis was conducted to measure mental health differences among children after controlling for socio-demographics. Chi-square analyses were used to assess differences in the prevalence of mental health problems among children. Results Bonferroni post hoc test showed that migrant and rural children reported significantly higher scores than urban peers in emotional symptoms, hyperactivity/inattention and total difficulties score (p p p = 0.046 and 0.024, respectively). Additionally, female gender, having insurance, seldom communicating with parents, and higher monthly household income were negatively associated with a higher total difficulties score. Conversely, children’s father with secondary education was positively associated with a higher total difficulties score. The prevalence of mental health problems among rural, migrant and urban children were 26.5, 18.8 and 15.0% (χ2 = 11.41, p = 0.003), respectively. Conclusions Rural and migrant children reported poorer mental health than urban children. Female gender, having insurance, seldom communicating with parents, and higher monthly household income were associated with better mental health of children. However, children’s father with secondary education was associated with poorer mental health of children. Given the different effects of socio-demographics, further support might be provided accordingly to improve the mental health of school-age children.

Background Xylanase is one of the most extensively used biocatalysts for biomass degradation. However, its low catalytic efficiency and poor thermostability limit its applications. Therefore, improving the properties of xylanases to enable synergistic degradation of lignocellulosic biomass with cellulase is of considerable significance in the field of bioenergy. Results Using fragment replacement, we improved the catalytic performance and thermostability of a GH10 xylanase, XylE. Of the ten hybrid enzymes obtained, seven showed xylanase activity. Substitution of fragments, M3, M6, M9, and their combinations enhanced the catalytic efficiency (by 2.4- to fourfold) as well as the specific activity (by 1.2- to 3.3-fold) of XylE. The hybrids, XylE-M3, XylE-M3/M6, XylE-M3/M9, and XylE-M3/M6/M9, showed enhanced thermostability, as observed by the increase in the T50 (3–4.7 °C) and Tm (1.1–4.7 °C), and extended t1/2 (by 1.8–2.3 h). In addition, the synergistic effect of the mutant xylanase and cellulase on the degradation of mulberry bark showed that treatment with both XylE-M3/M6 and cellulase exhibited the highest synergistic effect. In this case, the degree of synergy reached 1.3, and the reducing sugar production and dry matter reduction increased by 148% and 185%, respectively, compared to treatment with only cellulase. Conclusions This study provides a successful strategy to improve the catalytic properties and thermostability of enzymes. We identified several xylanase candidates for applications in bioenergy and biorefinery. Synergistic degradation experiments elucidated a possible mechanism of cellulase inhibition by xylan and xylo-oligomers.

BackgroundLysine post-translational modifications are important regulators of protein function. Proteomic and biochemical approaches have resulted in identification of several lysine modifications, including acetylation, crotonylation, and succinylation. Here, we developed an approach for surveying amide-bonded lysine modifications in the proteome of human tissues/cells based on the observation that many lysine modifications are amide-bonded and that theSalmonella entericadeacetylase, CobB, is an amidase.ResultsAfter the proteome of human tissues/cells was denatured and the non-covalently bonded metabolites were removed by acetone washes, and the amide-bonded modifiers were released by CobB and analyzed using liquid- and/or gas chromatography/mass spectrometry metabolomic analysis. This protocol, which required 3–4 days for completion, was used to qualitatively identify more than 40 documented and unreported lysine modifications from the human proteome and to quantitatively analyze dynamic changes in targeted amide-bonded lysine modifications.ConclusionsWe developed a method that was capable of monitoring and quantifying amide-bonded lysine modifications in cells of different origins.

Background Several studies have focused on the relationship between MMP-8 variants and cancer risk, but they have been unsuccessful in drawing reliable conclusions. Methods We employed odds ratio (OR) together with 95% confidence interval (CI) to assess the correlation between MMP-8 C-799 T, Lys460Thr, and Lys87Glu polymorphisms and cancer risk. We further employed in silico tools to evaluate the effect of MMP-8 expression on cancer susceptibility and overall survival time. Results A total of 8140 patients with malignant carcinoma and 10,529 healthy individuals (control) were enrolled. Overall, the analysis showed that the relationship between three MMP-8 variants and cancer susceptibility was not significant (allelic contrast, C-799 T: OR = 0.98, 95% CI = 0.92–1.04, Pheterogeneity = 0.068; Lys460Thr: OR = 0.94, 95% CI = 0.67–1.32, Pheterogeneity = 0.905; Lys87Glu: OR = 1.05, 95% CI = 0.93–1.18, Pheterogeneity = 0.968). Similar results were observed in subgroup analysis by ethnicity, cancer type, and source of control. In silico analysis indicated that MMP-8 expression was elevated in bladder cancer tissue compared to that in the control. However, both the higher and lower MMP-8 expression groups did not show an impact on the overall survival time of the patients. Conclusions MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not participant with the susceptibility of cancer.

Background KCNH family of potassium channels is responsible for diverse physiological functions ranging from the regulation of neuronal excitability and cardiac contraction to the regulation of cancer progression. KCNH channels contain a Per-Arn-Sim (PAS) domain in their N-terminal and cyclic nucleotide-binding homology (CNBH) domain in their C-terminal regions. These intracellular domains shape the function of KCNH channels and are important targets for drug development. Methods Here we describe a surface plasmon resonance (SPR)-based screening method aimed in identifying small molecule binders of PAS and CNBH domains for three KCNH channel subfamilies: ether-à-go-go (EAG), EAG-related gene (ERG), and EAG-like K+ (ELK). The method involves purification of the PAS and CNBH domains, immobilization of the purified domains on the SPR senor chip and screening small molecules in a chemical library for binding to the immobilized domains using changes in the SPR response as a reporter of the binding. The advantages of this method include low quantity of purified PAS and CNBH domains necessary for the implementation of the screen, direct assessment of the small molecule binding to the PAS and CNBH domains and easiness of assessing KCNH subfamily specificity of the small molecule binders. Results Using the SPR-based method we screened the Spectrum Collection Library of 2560 compounds against the PAS and CNBH domains of the three KCNH channel subfamilies and identified a pool of small molecules that bind to the PAS or CNBH domains. To further evaluate the effectiveness of the screen we tested the functional effect of one of the identified mEAG PAS domain specific small molecule binders on currents recorded from EAG channels. Undecylenic acid inhibited currents recorded from EAG channels in a concentration-dependent manner with IC50 of ~ 1 μM. Conclusion Our results show that the SPR-based method is well suited for identifying small molecule binders of KCNH channels and can facilitate drug discovery for other ion channels as well. Electronic supplementary material The online version of this article (10.1186/s40360-019-0324-8) contains supplementary material, which is available to authorized users.

Background Dexmedetomidine (DEX) has been reported to promote tumour metastases. However the underlying mechanisms remain unclear. The purpose of this study was to investigate whether DEX promotes tumour metastasis by inducing myeloid-derived suppressor cells (MDSC) in the context of surgery. Methods DEX was given to lung cancer patients and its effects on expansion of monocytic MDSC (M-MDSC) were studied in the context of surgery. Spontaneous tumour metastasis was induced in C57BL/6 mice and the effects of DEX on M-MDSC expansion and metastasis formation were assessed. Results DEX increased CD11b+CD33+HLA-DR–CD14+ M-MDSC in lung cancer patients after thoractomy. DEX-induced M-MDSC, in addition to have immunosuppressive activity, were more efficient in producing VEGF. Expansion of M-MDSC by DEX involved α2-adrenergic receptor. Using an experimental tumour metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and CD11b+Ly6ChighLy6G− M-MDSC during postoperative period were enhanced in DEX-treated mice. Promotion of tumour metastasis by DEX-induced M-MDSC involved VEGF, a key factor for tumour angiogenesis. Conclusions DEX induces the proliferation of M-MDSC during postoperative period in lung cancer patients and this cell population is qualified with potent proangiogenic ability. Treatment of mice with DEX expands M-MDSC and promotes tumour metastasis through the increasing production of VEGF. Electronic supplementary material The online version of this article (10.1186/s12967-018-1727-9) contains supplementary material, which is available to authorized users.

Background The collaborative working relationship of nurses with pharmacists has increasingly captured considerable attention. This study measured pharmacy and nursing students’ attitudes toward nurse-pharmacist collaboration at a university in China. Methods This cross-sectional study was conducted to assess the attitudes toward nurse-pharmacist collaboration using a self-developed scale delivered to a sample involving 202 nursing students and 258 pharmacy students enrolled in Wuhan University of Science and Technology. Results Completed instruments were returned by 192 nursing students (95.0% effective response rate) and 249 pharmacy students (96.5% effective response rate). The average students’ score of attitudes toward nurse-pharmacist collaboration was 78.85 out of a total of 100. No significance was found for the attitudes toward nurse-pharmacist collaboration between two professions or between gender. The college freshmen (first-year) students had the maximum scores suggesting the most positive attitude toward nurse-pharmacist collaboration, followed by second- and third-year students, while final-year (fourth-year) students had the least. Conclusion The students had somewhat positive attitudes toward nurse-pharmacist collaboration, but there is still room for improvement.

Background Lung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis. Thus, detecting lung cancer at an early stage could reduce mortality. Aberrant levels of circulating small non-coding RNAs (small ncRNAs) are potential diagnostic or prognostic markers for lung cancer. We aimed to identify plasma small ncRNA pairs that could be used for early screening and detection of lung adenocarcinoma (LAC). Results A panel of seven small ncRNA pair ratios could differentiate patients with LAC or benign lung disease from high-risk controls with an area under the curve (AUC) of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage (which included 50 patients with early-stage LAC, 35 patients with benign diseases and 29 high-risk controls) and an AUC of 90.2%, a sensitivity of 91.5% and a specificity of 80.4% at the validation stage (which included 44 patients with early-stage LAC, 32 patients with benign diseases and 51 high-risk controls). The same panel could distinguish LAC from high-risk controls with an AUC of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage and an AUC of 89.5%, a sensitivity of 85.4% and a specificity of 83.3% at the validation stage. Another panel of five small ncRNA pair ratios (different from the first) was able to differentiate LAC from benign disease with an AUC of 82.0%, a sensitivity of 81.1% and a specificity of 78.1% in the training cohort and an AUC of 74.2%, a sensitivity of 70.4% and a specificity of 72.7% in the validation cohort. Conclusions Several small ncRNA pair ratios were identified as markers capable of discerning patients with LAC from those with benign lesions or high-risk control individuals. Electronic supplementary material The online version of this article (10.1186/s12864-018-4862-z) contains supplementary material, which is available to authorized users.

Background Cryptocaryon irritans is an obligate parasitic ciliate protozoan that can infect various commercially important mariculture fish species and cause high lethality and economic loss. Current methods of controlling this parasite with chemicals or antibiotics are widely considered to be environmentally harmful. Piscidins with broad spectrum antibacterial, antifungal and antiviral activities were found to have potent activity against C. irritans. Little, however, has been understood about the killing mechanisms of piscidins in parasites. Results In total, 57.12, 50.44, 55.86 and 47.87 million raw reads were generated from untreated theront and trophont, and piscidin (Lc-pis) treated theront and trophont libraries, respectively. After de novo assembly, 966,609 unigenes were generated with an average length of 420 bp: among these, 618,629 unigenes showed identity with sequences in one or more databases, with some showing to be significantly manipulated by Lc-pis treatment. The species classification showed that more than 25.8% unigenes from trophonts were homologous to the large yellow croaker (Larimichthys crocea) and less than 3.8% unigenes from theronts were matched. The homologous unigenes demonstrated that the tissue from host could exist in trophonts and might be transported to parasite via vesicular transports. Our analysis showed that regulatory transcripts were involved in vesicular trafficking. Among transcripts induced by Lc-pis, most genes up-regulated in treated and untreated theronts were involved in cell migration and apoptosis related pathways. Few transcripts were found to be down-regulated in treated and untreated trophonts related to cell structure and migration after treatment. Conclusions This is the first transcriptome analysis of C. irritans exposed to Lc-pis, which enhanced the genomic resources and provided novel insights into molecular mechanisms of ciliates treated by cationic antimicrobial peptide. Our comprehensive transcriptome analysis can facilitate the identification of potential drug targets and vaccines candidates for controlling this devastating fish pathogen. Electronic supplementary material The online version of this article (10.1186/s12864-018-4565-5) contains supplementary material, which is available to authorized users.

Background Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood. Methods We analyzed messenger RNA (mRNA) microarray data from both invasive breast tumors (N = 602) and tumor-adjacent normal tissues (N = 508) from participants diagnosed with breast cancer in the Nurses’ Health Study (NHS) and NHSII. Multivariable linear regression, controlling for other known breast cancer risk factors, was used to identify differentially expressed genes by pre-diagnostic alcohol intake. For pathway analysis, we performed gene set enrichment analysis (GSEA). Differentially expressed genes or enriched pathway-defined gene sets with false discovery rate (FDR)

Background Long non-coding RNAs (lncRNAs) are aberrantly expressed in many types of human cancer including pancreatic cancer (PC) and correlated with tumorigenesis and cancer prognosis, whereas knowledge about regulatory mechanism of lncRNA expression is few known. This study aimed to explore whether polymorphisms in lncRNAs genes are associated with PC susceptibility by affecting its expression. Methods We first genotyped three common single-nucleotide polymorphisms (SNPs) of lncRNA genes (HOTTIP rs1859168, HOTAIR rs4759314, and H19 rs217727) in 416 paired PC patients and controls, and then validated the results in another 505 paired PC patients and controls. The genotype-phenotype correlation was examined in 50 PC tissue samples with different genotypes as well as by luciferase reporter assay. Results In the discovery set, only the HOTTIP rs1859168 A > C showed to be significantly associated with a reduced PC risk (CC vs AA: odds ratio (OR) = 0.71, 95% confidence interval (95%CI) = 0.57–0.88, P = 0.002; recessive model: adjusted OR = 0.51, 95%CI = 0.38–0.68, P C polymorphism may decrease the PC risk by down-regulating the HOTTIP expression.

Background Diet composition (yeast:carbohydrate ratio) is an important determinant of growth, development, and reproduction. Recent studies have shown that decreased yeast intake elicits numerous transcriptomic changes and enhances somatic maintenance and lifespan, which in turn reduces reproduction in various insects. However, our understanding of the responses leading to a decrease in yeast ratio to 0% is limited. Results In the present study, we investigated the effects of a sugar-only diet (SD) on the gene expression patterns of the oriental fruit fly, Bactrocera dorsalis (Hendel), one of the most economically important pests in the family Tephritidae. RNA sequencing analyses showed that flies reared on an SD induced significant changes in the expression levels of genes associated with specific metabolic as well as cell growth and death pathways. Moreover, the observed upregulated genes in energy production and downregulated genes associated with reproduction suggested that SD affects somatic maintenance and reproduction in B. dorsalis. As expected, we observed that SD altered B. dorsalis phenotypes by significantly increasing stress (starvation and desiccation) resistance, decreasing reproduction, but did not extend lifespan compared to those that received a normal diet (ND) regime. In addition, administration of an SD resulted in a reduction in antioxidant enzyme activities and an increase in MDA concentrations, thereby suggesting that antioxidants cannot keep up with the increase in oxidative damage induced by SD regime. Conclusions The application of an SD diet induces changes in phenotypes, antioxidant responses, and gene expressions in B. dorsalis. Previous studies have associated extended lifespan with reduced fecundity. The current study did not observe a prolongation of lifespan in B. dorsalis, which instead incurred oxidative damage. The findings of the present study improve our understanding of the molecular, biochemical, and phenotypic response of B. dorsalis to an SD diet. Electronic supplementary material The online version of this article (doi:10.1186/s12862-017-1045-5) contains supplementary material, which is available to authorized users.

Background Although tibial plateau fracture is an uncommon injury, its regulation is challenging and there are some influencing factors, including the effects of severe bone displacement, depression and cancellous bone cartilage, and inevitable cartilage damage. And GIT1 plays an important role in bone mass and 78 osteoblast cell migration. Methods The study used 72 C57/BL6 mice. A tibial plateau fracture model was established by using mice with the same number of GIT1 gene deletions (the experimental group) and their wild-type littermates (the control group). Joint and bone callus recovery were evaluated by X-ray and CT thin layer scans. Micro CT assay and histomorphometry were conducted in order to evaluate the volume of newly formed blood vessels. Type II collagen expression in tibial tissues after tibial plateau fracture were detected by immunohistochemistry after 7, 14 and 21 days. The number of proliferating cell nuclear antigen (PCNA) positive cells after tibial plateau fracture was tested by immunohistochemistry after 14 and 21 days. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was conducted after 14 and 21 days in order to test chondrocyte apoptosis in tibial tissues after tibial plateau fracture. Results The GIT1 gene deletion group mice spent less time on the rotating rod than the control group mice (P

Background Mouse double minute 2 (MDM2) and vascular endothelial growth factor (VEGF) are important molecules involved in tumor progression. We researched potential inhibitors that simultaneously target MDM2 and VEGF. In our recent study involving the performance of high-throughput screening with a fluorescence polarization assay, gossypol was identified as one of the top hits that inhibit protein-RNA binding activity. Because MDM2 is an RNA-binding protein and its targets include VEGF mRNA, we investigated whether gossypol has an inhibitory effect on MDM2-VEGF. Methods UV cross-linking and RNA binding assay, isothermal titration calorimetry assay, and ubiquitination assay were performed to determine mechanisms by which gossypol functions as a dual inhibitor of MDM2 and VEGF. The effect of gossypol on MDM2 and VEGF expression, cancer cell apoptosis, tumor growth and VEGF-mediated angiogenesis were studied in vitro and in vivo in different human breast cancer models with a different p53 status. Results We observed that gossypol inhibited expression of both MDM2 and VEGF in human breast cancer cells with either wild-type or mutant p53. A nechanistic study further demonstrated that, through disrupting the interaction between MDM2 protein and VEGF mRNA, gossypol induced MDM2 self-ubiquitination and decreased VEGF translation simultaneously, which resulted in both apoptosis and anti-angiogenesis effects. In vitro, regardless of p53 status, gossypol induced cancer cell apoptosis. In nude mouse xenograft in vivo models, gossypol suppressed tumor growth and VEGF-mediated angiogenesis. Conclusion Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer. Our study reveals a novel mechanism by which gossypol functions as an anticancer agent. We believe that MDM2-VEGF targeting represents a novel strategy for improving cancer outcome.

Background Polyploidy and hybridization are both recognized as major forces in evolution. Most of our current knowledge about differences in gene regulation in polyploid hybrids comes from plant studies. The gene expression of diverged genomes and regulatory interactions are still unclear in lower vertebrates. Results We generated 229 million cleaned reads (42.23 Gbp) from triploid of maternal grass carp (Ctenopharyngodon idellus, Cyprininae, 2n = 48) × paternal blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n = 48) and their diploid parents using next-generation sequencing. In total, 157,878 contigs were assembled and 15,444 genes were annotated. We examined gene expression level changes among the parents and their triploid offspring. The mechanisms of dosage compensation that reduced triploid expression levels to the diploid state were determined in triploid fish. In this situation, novel gene expression and gene silencing were observed. Then, we established a model to determine the extent and direction of expression level dominance (ELD) and homoeolog expression bias (HEB) based on the relative expression level among the parents and their triploid offspring. Conclusions Our results showed that the genome-wide ELD was biased toward maternal genome in triploid. Extensive alterations in homoeolog expression suggested a combination of regulatory and epigenetic interactions through the transcriptome network. Additionally, the expression patterns of growth genes provided insights into the relationship between the characteristics of growth and underlying mechanisms in triploids. Regulation patterns of triploid state suggest that various expression levels from the initial genomic merger have important roles in adaptation. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3424-5) contains supplementary material, which is available to authorized users.

Background Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. Results In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19–82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p

Background Parasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics. We have previously demonstrated that Schistosoma japonicum HSP60-derived peptide SJMHE1 induces CD4+CD25+ regulatory T-cells (Tregs) and that adoptively transferred SJMHE1-induced CD4+CD25+ Tregs inhibit delayed-type hypersensitivity (DTH) in mice. However, multiple concerns regarding this method render this treatment unsuitable. To gain further insights into the potential effects of SJMHE1, we used ovalbumin (OVA)-induced DTH and evaluated the effect of SJMHE1 on DTH mice. Methods BALB/c mice were sensitised with OVA alone or combined with SJMHE1 and then challenged with OVA to induce DTH. We first analysed the potential effects of SJMHE1 by measuring DTH responses, T-cell responses, cytokine secretion, and Treg proportions. We then evaluated the expression levels of IL-10 and TGF-β1 in CD4+CD25+ T-cells during DTH and Treg generation to identify the mechanism by which SJMHE1 suppresses DTH. Results SJMHE1 modulated the effector response against OVA-induced DTH and stimulated the production of the anti-inflammatory cytokines IL-10 and TGF-β1 in immunised mice through a mechanism involving CD4+CD25+ Tregs. SJMHE1-induced CD4+CD25+ Tregs expressed high levels of CTLA-4, IL-10, and TGF-β1, which substantially contributed to the suppressive activity during DTH. The administration of SJMHE1 to DTH in mice led to the expansion of CD4+CD25+ Tregs from CD4+CD25− T-cells in the periphery, which inhibited DTH responses. Conclusions Our study proves that the parasite-driven peptide suppresses DTH in mice, which may confer a new option for inflammation treatment.

Background Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and also assessed their cumulative effects and predictive value for obesity risk in Chinese children. Methods We genotyped 40 single nucleotide polymorphisms (SNPs) and conducted association analyses for 32/40 SNPs with an estimated minor allele frequency >1 % in 2 030 unrelated Chinese children, including 607 normal-weight, 718 overweight, and 705 obese individuals from two cross-sectional study groups. Logistic regression and linear regression under the additive model were used to examine associations, and the area under the receiver operating characteristic curve (AUCROC) was reported as prediction summary. Results We identified obesity association for 6 SNPs near SEC16B, RBJ, CDKAL1, TFAP2B, MAP2K5 and FTO (odds ratios (ORs) ranged from 1.19 to 1.41, nominal two-sided P-values

Background With regard to the global childhood obesity epidemic, it is imperative that effective lifestyle interventions are devised to combat childhood obesity. This paper describes the development and implementation of a comprehensive (a combination of diet and physical activity (PA)), social cognitive behaviour modification intervention using accelerometry and a dietary diary to tackle child overweight and obesity. The comprehensive intervention effect was evaluated in a comparison with diet only, PA only and a no-treatment control group. Methods A pilot study was conducted with a non-randomized cluster design. Four hundred thirty-eight overweight and obese children aged 7–12 years from ten primary schools in Beijing were recruited to receive a one-year intervention. Participants were allocated into one of four groups: the comprehensive intervention group; the PA only group (Happy 10 program); the diet only group (nutrition education program); and a control group. The effects of intervention on adiposity, blood pressure, and biochemical indicators were assessed by examining 2-way interactions (time × intervention) in linear mixed models. Means and 95 % confidence intervals (CI) for the adjusted changes between post-intervention and baseline relative to changes in the control group were calculated and reported as effect sizes. Results The percentage of body fat in the comprehensive intervention group showed a significant relative decrease (adjusted change: −1.01 %, 95 % CI: (−1.81, −0.20) %) compared with the PA only, diet only or control groups (P

Background This study was aimed to investigate whether regeneration of periodontal ligament (PDL) like tissue could be promoted by stromal cell-derived factor-1 (SDF1) and bone morphogenetic protein-7 (BMP7) induced cell homing in delayed replantation of avulsed teeth. Methods Canine mandibular premolar teeth were first extracted and air-dried for 2 h followed by complete detachment of their PDL tissues. The crown and pulp of the teeth were also removed. Twenty-four roots divided into two groups (n = 12/group) were used for the following in vivo transplantation. The roots of Group A were treated with 17 % EDTA for 24 h to achieve demineralization, and then coated with SDF1 and BMP7 supplemented collagen solution. The roots of Group B were similarly treated except being coated with a pristine collagen solution. The above roots were transplanted in the sockets that formed previously during tooth extraction. At 6 months’ post-operation, PDL-like tissue composed of spindle-shaped cells, capillaries and highly organized collagen fibers was observed in the interstitial space between the avulsed root surface and surrounding alveolar bone in Group A. The neo-fibers inserted deeply and perpendicularly into the cementum and adjacent bone. The periodontium-like characteristics of the neo-tissue was confirmed by immunohistochemical staining for collagen I, fibronectin and osteocalcin. Results A high incidence of PDL re-establishment as 42 % was achieved for samples of Group A. However, no PDL-like tissue was found but root ankylosis and replacement resorption as well as inflammatory resorption was observed in the replanted roots of Group B. Conclusions It can be confirmed that avulsed teeth could be successfully rescued even in delayed transplantation to avoid dentoalveolar ankylosis or replacement resorption via the current developed cell homing method. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0719-2) contains supplementary material, which is available to authorized users.

There is a rapidly increasing amount of de novo genome assembly using next-generation sequencing (NGS) short reads; however, several big challenges remain to be overcome in order for this to be efficient and accurate. SOAPdenovo has been successfully applied to assemble many published genomes, but it still needs improvement in continuity, accuracy and coverage, especially in repeat regions.To overcome these challenges, we have developed its successor, SOAPdenovo2, which has the advantage of a new algorithm design that reduces memory consumption in graph construction, resolves more repeat regions in contig assembly, increases coverage and length in scaffold construction, improves gap closing, and optimizes for large genome.Benchmark using the Assemblathon1 and GAGE datasets showed that SOAPdenovo2 greatly surpasses its predecessor SOAPdenovo and is competitive to other assemblers on both assembly length and accuracy. We also provide an updated assembly version of the 2008 Asian (YH) genome using SOAPdenovo2. Here, the contig and scaffold N50 of the YH genome were ~20.9 kbp and ~22 Mbp, respectively, which is 3-fold and 50-fold longer than the first published version. The genome coverage increased from 81.16% to 93.91%, and memory consumption was ~2/3 lower during the point of largest memory consumption.

Background: Patients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity. Results: In the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway. Conclusions: We provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.

Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) have been used for patients with hepatocellular carcinoma (HCC). However, which therapy is superior remains to be further elucidated. We aimed to conduct a systematic review to assess survival and local tumor recurrence rate with RFA compared with PEI therapy for HCC.We conducted systematic review and meta-analysis of randomized controlled trials (RCTs) published up to 2014 in PubMed, MEDLINE, EMBASE, EBSCO, Springer, Ovid and the Cochrane library. Only RCTs that evaluated survival rate and occurrence of HCC between RFA and PEI therapy were included. The OR (odds ratio) with a 95% confidence interval (CI) was calculated by the Revman 5.0 software.A total of six studies including 983 HCC patients were eligible for this analysis. The survival rate showed a significant benefit under RFA therapy over PEI at 1-year (P = 0.02, OR = 1.88, 95% CI: 1.09 to 3.22), 2-years (P = 0.0003, OR = 2.06, 95% CI: 1.39 to 3.05) and 3-years (P = 0.0007, OR = 1.68, 95% CI: 1.25 to 2.27). Likewise, RFA achieved significantly lower rates of local tumor recurrence over PEI at 1-year (P = 0.002, OR = 0.43, 95% CI: 0.26 to 0.73), 2-year (P = 0.03, OR = 0.33, 95% CI: 0.12 to 0.88) and 3-year (P = 0.003, OR = 0.61, 95% CI: 0.43 to 0.84).The current evidence suggests that RFA is superior to PEI in better survival and local disease control for small HCCs5 cm in diameter and that RFA is worthy of promotion in clinical applications.