DNA double-strand break repair capacity and its pathway gene variants predict the risk and prognosis of lung cancer.

OBJECTIVES: This study aims to investigate the association between DNA double-strand breaks (DSBs) repair capacity, variations in DSBs-related genes, and the occurrence and prognosis of lung cancer in the Chinese population. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 98 lung cancer patients and 60 healthy individuals. The individual DSBs repair capacity was assessed by measuring changes in γ-H2AX levels after treatment with etoposide. Exonic sequencing of 45 DSBs-related genes was performed on PBMC DNA. Logistic regression analysis was conducted to examine the relationship between lung cancer risk and DSBs repair capacity as well as germlines gene variations. Survival analysis employed the Cox proportional hazards regression model, Kaplan-Meier method, and Log-rank test. RESULTS: Lower DSBs repair capacity predicted an increased risk of developing lung cancer (OR = 0.94, 95 %CI = 0.917-0.964, P＜0.001). Among lung cancer patients, higher DSBs repair capacity was associated with shorter progression-free survival (PFS) during first-line treatment (HR = 1.80, 95 %CI = 1.10-3.00, P = 0.031). Patients with BRCA1 mutations had shorter overall survival (OS) (HR = 1.92, 95 %CI = 1.12-3.28, P = 0.018). Patients with FOXO3 mutations had shorter PFS (HR = 4.23, 95 %CI = 1.44-12.36, P = 0.009). Analysis of patients treated with immune checkpoint inhibitors (ICIs) indicated that LIG4 mutations were associated with shorter PFS (HR = 2.90, 95 %CI = 1.00-8.10, P = 0.041). CONCLUSIONS: This study concludes that assessing DSBs repair capacity holds promise for predicting both lung cancer risk and prognosis in the Chinese population. Further large-scale studies and functional validation of specific gene mutations related to double-strand breaks are necessary for confirmation.

Analysis of initial sandplay characteristics among university students with different levels of loneliness.

BACKGROUND AND OBJECTIVE: Loneliness is detrimental to mental health, with university students at higher risk of feeling lonely than other population groups. The mental health of college students is a hot topic at present. Despite numerous studies exploring interventions for loneliness among university students. However, little research has explored early psychological manifestations of university students with different levels of loneliness. Despite numerous studies exploring interventions for loneliness among university students, little research has explored early psychological manifestations of university students with different levels of loneliness. Initial sandplay is a good tool to reveal psychological activity. Therefore, our study aims to explore the characteristics of initial sandplay application among university students with different levels of loneliness. METHODS: We recruited 60 volunteers from a university to perform a sandplay experiment from January to April 2021. The UCLA Loneliness Scale measured the levels of loneliness. These 60 participants were divided into the experimental group (n = 30) and control group (n = 30) according to their levels of loneliness. The experimental group included participants with a scale score of more than 44. Other participants with a scale score of less than 44 belong to the control group. We recorded their sandplay artwork and statistically analyzed it by the Sandplay Process Record Form. Group comparisons were performed using the t-test or Wilcoxon rank-sum test for continuous variables, and the chi-square test or Fisher's exact test for categorical variables. The logistic regression analysis by forward stepwise method was conducted to analyze the sandplay theme features for loneliness. RESULTS: Regarding the sandplay tools, the experimental group used fewer transportation tools (t=-3.608, p < 0.01) and more natural elements (t = 2.176, p < 0.05) than the control group. Moreover, the experimental group created more natural scenes (χ2 = 4.310, p < 0.05) and used less of the lower left (χ2 = 4.593, p < 0.05) and lower right (χ2 = 5.934, p < 0.05) spaces. With regards to sand changes, the experimental group was less likely than the control group to make substantial changes (χ2 = 5.711, p < 0.05) and more likely to make almost no changes (χ2 = 4.022, p < 0.05). In terms of the themes, the experimental group was more likely to exhibit sandplay artwork themes of emptiness (χ2 = 8.864, p < 0.05) and neglect (χ2 = 6.667, p < 0.05), and less likely to show themes of energy (χ2 = 5.079, p < 0.05). In the logistic regression analysis of the sandplay themes, emptiness (OR = 5.714, 95%CI: 1.724-18.944, p = 0.003) and neglect (OR = 7.000, 95%CI: 1.381-35.479, p = 0.010) were demonstrated a nominal association with high levels of loneliness among both groups (F = 16.091, p < 0.01, ΔR2 = 0.193), but failed to pass the Bonferroni testing correction (p threshold < 0.0025). CONCLUSION: University students with higher degree of loneliness do not like to drastic changes and prefer to use natural elements in element selection, while the control group likes to drastic changes and prefers to use transportation tools in element selection. Regression analysis of sandplay theme features revealed emptines and neglect may as significant associated factors for loneliness. We propose sandplay characteristics can help identify university students with different levels of loneliness during psychological evaluations. Therefore, it is important that the school and healthcare systems assist college students in identifying the loneliness through initial sandplay and carrying on the necessary psychological counseling to the lonely student population.

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or "DTRs"). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population.

Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells.

Virtually all living cells are encased in glycans. They perform key cellular functions such as immunomodulation and cell-cell recognition. Yet, how their composition and configuration affect their functions remains enigmatic. Here, we constructed isogenic capsule-switch mutants harboring 84 types of capsular polysaccharides (CPSs) in Streptococcus pneumoniae. This collection enables us to systematically measure the affinity of structurally related CPSs to primary human nasal and bronchial epithelial cells. Contrary to the paradigm, the surface charge does not appreciably affect epithelial cell binding. Factors that affect adhesion to respiratory cells include the number of rhamnose residues and the presence of human-like glycomotifs in CPS. Besides, pneumococcal colonization stimulated the production of interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractantprotein-1 (MCP-1) in nasal epithelial cells, which also appears to be dependent on the serotype. Together, our results reveal glycomotifs of surface polysaccharides that are likely to be important for colonization and survival in the human airway.

Abscisic acid plays a key role in the mechanism of photosynthetic and physiological response effect of Tetrabromobisphenol A on tobacco.

The toxicity of bromide to animals and microorganisms has been widely studied, but the mechanism by which bromide toxicity affects plants is rarely studied. This study used the bromophenol compound Tetrabromobisphenol A (TBBPA) as a representative of bromide to explore the physiological and molecular response mechanism of tobacco leaves to TBBPA. In addition, physiological determination, transcriptomics, weighted gene co-expression network analysis (WGCNA) analysis, and random forest prediction model were conducted. The findings from this study indicated that TBBPA limited the photoreaction process by destroying the light-catching antenna protein of tobacco leaves, the activity of the photosystem reaction centers (PSII and PSI), and the linear electron transport efficiency. TBBPA also reduced the rate of the Calvin-Benson cycle by inhibiting the activities of gene such as Rubisco, PGK, and TPI, and finally destroyed the photosynthesis process. Although cyclic electron transport was enhanced under stress conditions, it could not reverse the damage caused by TBBPA on photosynthesis. TBBPA exposure resulted in the accumulation of reactive oxygen species (ROS) in tobacco leaves, and the activities of Superoxide dismutase (SOD), Ascorbate peroxidase (APX), and Glutathione peroxidase (GPX) and their coding genes were significantly down-regulated. Although POD activity and proline (Pro) content were increased, they were insufficient to remove excess O2·- free radicals to relieve ROS stress. WCGNA and random forest models predicted that the damage of TBBPA to the above processes in tobacco was closely related to the increase in abscisic acid (ABA) content. TBBPA affects the Calvin cycle by inducing ABA signal transduction and stomatal closure, which leads to a series of chain reactions, such as electron transport chain obstruction, excess of ROS, decrease in chlorophyll synthesis, and photosystem reaction center damage.

Characteristics in Initial Sandplay of Optimal and Non-optimal Family Functioning Among High School Students.

Objective: The purpose of this study is to explore the characteristics of the initial sandplay of high school students with poor family function, by studying the initial sandplay of high school students with different levels of family function, so as to provide the basics for the psychological assessment and intervention of high school students. Significance: To provide data support for high school students' mental health education and sandplay therapy, and to apply sandplay as an intervention method to play a healing role in high school mental health work. Methods: High school students (N = 345) were divided into 11 groups and participated in a sandplay experiment for 8 weeks from February to March 2021. Each group completed the Chinese version of the Epstein et al. Family Assessment Device. Samples with scores of one standard deviation below and above the sample mean were placed in the low family functioning group (n = 30; 15 girls) or high family functioning group (n = 30; 15 girls), respectively. The initial sandplay was evaluated on multiple dimensions using an established coding system. Results: Samples with low family functioning used fewer animal figurines in their sandplay (t = 2.176, p < 0.05); had more family scenes (χ2 = 4.356, p < 0.05); fewer rural scenes (χ2 = 4.344, p < 0.05); and fewer healing themes (t = -2.336, p < 0.05). In particular, there were fewer examples of connected healing themes (χ2 = 7.500, p < 0.05); in-depth healing themes (χ2 = 5.455, p < 0.05); and more hindered trauma themes (χ2 = 4.812, p < 0.05). Logistic regression analysis was conducted using the sandplay characteristics as predictors of group membership. Using forward stepwise selection, themes of hindered trauma (B = -2.030) and connected healing (B=1.765) were shown to be significant predictors of group membership (F = 17.784, P < 0.01, ΔR 2 = 0.214). Conclusion: Students who reported high and low family functioning showed significant differences in their sandplay characteristics. We propose sandplay characteristics can help identify low family functioning of adolescents during psychological evaluations.

Uncovering Novel Viral Innate Immune Evasion Strategies: What Has SARS-CoV-2 Taught Us?

The ongoing SARS-CoV-2 pandemic has tested the capabilities of public health and scientific community. Since the dawn of the twenty-first century, viruses have caused several outbreaks, with coronaviruses being responsible for 2: SARS-CoV in 2007 and MERS-CoV in 2013. As the border between wildlife and the urban population continue to shrink, it is highly likely that zoonotic viruses may emerge more frequently. Furthermore, it has been shown repeatedly that these viruses are able to efficiently evade the innate immune system through various strategies. The strong and abundant antiviral innate immunity evasion strategies shown by SARS-CoV-2 has laid out shortcomings in our approach to quickly identify and modulate these mechanisms. It is thus imperative that there be a systematic framework for the study of the immune evasion strategies of these viruses, to guide development of therapeutics and curtail transmission. In this review, we first provide a brief overview of general viral evasion strategies against the innate immune system. Then, we utilize SARS-CoV-2 as a case study to highlight the methods used to identify the mechanisms of innate immune evasion, and pinpoint the shortcomings in the current paradigm with its focus on overexpression and protein-protein interactions. Finally, we provide a recommendation for future work to unravel viral innate immune evasion strategies and suitable methods to aid in the study of virus-host interactions. The insights provided from this review may then be applied to other viruses with outbreak potential to remain ahead in the arms race against viral diseases.

Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection In Vitro, despite Eliciting a Prolonged Antiviral Response.

The dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia. IMPORTANCE Increasing medical attention has been drawn to the persistence of symptoms (long-COVID syndrome) or live virus shedding from subsets of COVID-19 patients weeks to months after the initial onset of symptoms. In vitro approaches to model viral or symptom persistence are needed to fully dissect the complex and likely varied mechanisms underlying these clinical observations. We show that in vitro differentiated human NECs are persistently infected with SARS-CoV-2 for up to 28 dpi. This viral replication occurred despite the presence of an antiviral gene signature across all NEC cell types even at 28 dpi. This indicates that epithelial cell intrinsic antiviral responses are insufficient for the clearance of SARS-CoV-2, implying an essential role for tissue-resident and infiltrating immune cells for eventual viral clearance from infected airway tissue in COVID-19 patients.

Novel fractional-order decentralized control for nonlinear fractional-order composite systems with time delays.

A novel decentralized non-integer order controller applied on nonlinear fractional-order composite system(NFOCS) is proposed. In addition, some novel results for the asymptotic stabilization are shown with fractional parameter α∈0,1. First, we derive certain novel results useful for the Mittag-Leffler function. Then, we design a new decentralized fractional-order controller for the NFOCS according to the novel results applied to Mittag-Leffler function. Next, this novel asymptotic stabilization condition has been proposed. Compared with other controllers our controller has wider control gain range and weaker requirements. Moreover, we solve the asymptotic stabilization problem of the NFOCS with time delays via the novel controller. In the end, four general examples are performed to show the progressiveness of the new fractional-order decentralized controller.

Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection.

The early interactions between the nasal epithelial layer and the innate immune cells during viral infections remains an under-explored area. The significance of innate immunity signaling in viral infections has increased substantially as patients with respiratory infections who exhibit high innate T cell activation show a better disease outcome. Hence, dissecting these early innate immune interactions allows the elucidation of the processes that govern them and may facilitate the development of potential therapeutic targets and strategies for dampening or even preventing early progression of viral infections. This protocol details a versatile model that can be used to study early crosstalk, interactions, and activation of innate immune cells from factors secreted by virally infected airway epithelial cells. Using an H3N2 influenza virus (A/Aichi/2/1968) as the representative virus model, innate cell activation of co-cultured peripheral blood mononuclear cells (PBMCs) has been analyzed using flow cytometry to investigate the subsets of cells that are activated by the soluble factors released from the epithelium in response to the viral infection. The results demonstrate the gating strategy for differentiating the subsets of cells and reveal the clear differences between the activated populations of PBMCs and their crosstalk with the control and infected epithelium. The activated subsets can then be further analyzed to determine their functions as well as molecular changes specific to the cells. Findings from such a crosstalk investigation may uncover factors that are important for the activation of vital innate cell populations, which are beneficial in controlling and suppressing the progression of viral infection. Furthermore, these factors can be universally applied to different viral diseases, especially to newly emerging viruses, to dampen the impact of such viruses when they first circulate in naïve human populations.

Dual-layer detector spectral CT-a new supplementary method for preoperative evaluation of glioma.

PURPOSE: To investigate the value of the iodine concentration (IC) measured by dual-layer detector spectral CT (DLDSCT) in evaluating the factors related to the treatment scheme and survival prognosis of patients with glioma. METHODS: From 2018 to 2019, we prospectively collected the data of 99 patients with glioma. The degree of CT enhancement and the IC of low grade gliomas (LGGs, II), high grade gliomas (HGGs, III and IV), grade II and III gliomas, were compared. The predictive performance of the degree of CT enhancement and IC was examined via receiver operating characteristic (ROC) analysis. The correlations between IC and Ki-67 labeling index, isocitrate dehydrogenase (IDH) mutation, chromosome 1p/19q deletion status of the tumor were examined. RESULTS: Both IC and the degree of CT enhancement of patients with HGG were significantly higher than those of patients with LGG (p < 0.001; χ2 =41.707, p <  0.001); IC had large area under the ROC curve for diagnostic HGG (0.931; 95 % CI: 0.882-0.979; p <  0.001). The IC in the grade III gliomas was significantly higher than that in grade II gliomas (p < 0.001); IC had a large area under the ROC curve for diagnostic grade III gliomas (0.865; 95 % CI: 0.779-0.952; p <  0.001). There was a significant positive correlation between IC and Ki-67 LI (r = 0.679; p < 0.001). CONCLUSIONS: The DLDSCT technology can be used as a supplementary method to provide more information for preoperative grading of the gliomas and the prognosis assessment of the patients.

Long non-coding RNA Sox2 overlapping transcript (SOX2OT) promotes multiple myeloma progression via microRNA-143-3p/c-MET axis.

Long non-coding RNA Sox2 overlapping transcript (SOX2OT) was reported to be involved in progression of multiple cancers. However, the role and mechanism of SOX2OT in multiple myeloma (MM) has yet to be unravelled. In the present study, elevated SOX2OT levels are reported in MM cell lines and patient samples as compared to normal plasma cells (nPCs) and healthy donors, respectively. Knock-down of SOX2OT led to a significant inhibition of cell proliferation, arrested cells at G0/G1 phase and induced cell apoptosis in MM samples in vitro, as well as slowed the growth of tumours in vivo. Additionally, our data indicated that SOX2OT functioned as a competing endogenous RNA (ceRNA) in MM cells that regulated miR-144-3p expression. Repression of miR-144-3p reversed the inhibition of MM development due to SOX2OT knock-down. Our data also revealed that SOX2OT regulated the expression of the cellular-mesenchymal to epithelial transition factor (c-MET, a known target of miR-143-3p) by functioning as a sponge of miR-144-3p in MM samples. These data support that SOX2OT promotes MM progression through regulating the miR-144-3p/c-MET axis, suggesting that SOX2OT might be as a potential therapeutic target for MM.

The use of DNA repair genes as prognostic indicators of gastric cancer.

DNA repair genes can be used as prognostic biomarkers in many types of cancer. We aimed to identify prognostic DNA repair genes in patients with gastric cancer (GC) by systematically bioinformatic approaches using web-based database. Global gene expression profiles from altogether 1,325 GC patients' samples from six independent datasets were included in the study. Clustering analysis was performed to screen potentially abnormal DNA repair genes related to the prognosis of GC, followed by unsupervised clustering analysis to identify molecular subtypes of GC. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular key genes in molecular subtypes were identified based on changes in expression correlation. Multivariate Cox proportional hazard analysis was used to find the independent prognostic gene. Kaplan-Meier method and log-rank test was used to estimate correlations of key DNA repair genes with GC patients'overall survival. There were 57 key genes significantly associated to GC patients' prognosis, and patients were stratified into three molecular clusters based on their expression profiles, in which patients in Cluster 3 showed the best survival (P < 0.05). After a three-phase training, test and validation process, the expression profile of 13 independent key DNA repair genes were identified can classify the prognostic risk of patients. Compared with patients with low-risk score, patients with high risk score in the training set had shorter overall survival (P < 0.0001). Furthermore, we verified equivalent findings by these key DNA repair genes in the test set (P < 0.0001) and the independent validation set (P = 0.0024). Our results suggest a great potential for the use of DNA repair gene profiling as a powerful marker in prognostication and inform treatment decisions for GC patients.

Intra- and Interspecific Variation in Production of Bile Acids That Act as Sex Pheromones in Lampreys.

Pheromones are important sexual signals in most animals, but research into their evolution is largely biased toward insects. Lampreys are a jawless fish with a relatively well-understood pheromone communication system, and they offer a useful opportunity to study pheromone evolution in a vertebrate. Once sexually mature, male sea lamprey (Petromyzon marinus) and likely other lampreys produce and release bile acids that act as sex pheromones. Spawning males do not feed and therefore produce bile acids primarily for sexual communication, whereas larvae produce the same bile acids but for digestion, offering an opportunity to compare the evolution of bile acids produced for sexual versus nonsexual functions. We profiled eight pheromone-related bile acids in livers from larvae and males and determined the effect of life stage on intra- and interspecific variation in bile acid production. Our results indicate less variation among males than larvae within P. marinus but more variation among species for males than larvae. We postulate that bile acid production in males is shaped by directional or stabilizing selection that reduces variance within P. marinus and directional or disruptive selection that promotes diversification across species. Although our results offer support for the role of sexual selection in the evolution of lamprey pheromones, they do not eliminate possible roles of other aspects of lamprey ecology.

The antitumor effect of resveratrol on nasopharyngeal carcinoma cells.

The anti-tumor effect of resveratrol has been observed in many cancers. Here, we examined the anti-tumor activity of resveratrol in human nasopharyngeal carcinoma (NPC) cells. Resveratrol, in a dose-dependent manner, inhibited proliferation related proteins (Ki67, PCNA), and cell proliferation, and reduced apoptosis related proteins (cleaved caspase-3, cleaved caspase-9) and apoptosis in nasopharyngeal carcinoma cells. Resveratrol treatment inhibited the increased-expression of Survivin in NPC cells, while the overexpressed Survivin counteracted the effect of resveratrol on cell proliferation and apoptosis in NPC cells, thus establishing Resveratrol-induced reduction in increased-survivin in NPC cells as the underlying mechanism. These findings show that resveratrol can be used to modify the cell growth and death in NPC cells.

The correlation between gene polymorphisms of endothelial nitric oxide synthase and aneurismal subarachnoid hemorrhage.

To discuss the association of the T786C and G894T polymorphisms of endothelial nitric oxide synthase (eNOS) with the occurrence and prognosis of aneurismal subarachnoid hemorrhage (aSAH). One hundred sixty-nine patients with aSAH were collected as the case group, which was divided into the good prognosis group and adverse prognosis group according to the condition 3 months after the treatment. One hundred fifty-six healthy volunteers were collected as the control group. The allele and genotype of T786C and G894T polymorphisms of eNOS were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequency of eNOS were compared between different groups. And then, the risk factors of aSAH occurrence and prognosis were analyzed by using the logistic regression model. Both the genotype and allele frequency distributions of T786C and G894T between the case group and control group were significantly different (P < 0.05). There were significant differences in the distribution of G894T and T786C allele frequency and G894T genotype between the good prognosis group and adverse prognosis group, and there was no difference in T786C genotype. The results of the logistic regression analysis indicated that T786C and G894T polymorphisms of eNOS were independent influencing factors on the occurrence of aSAH and the G894T polymorphism was also closely related to the prognosis. T786C and G894T polymorphisms of eNOS gene were correlated with the occurrence and prognosis of aSAH, and the G894T polymorphism might be an independent influencing factor.

Transposable element dysregulation in systemic lupus erythematosus and regulation by histone conformation and Hsp90.

Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons. We used RNA-seq to define transposable element families and subfamilies in three cell types in SLE and found diverse effects on transposable element expression in the three cell types and even within a given family of transposable elements. When potential mechanisms were examined, we found that Hsp90 inhibition could drive increased expression of multiple type of transposable elements. Both direct inhibition and the delivery of a heat shock itself, which redirects heat shock regulators (including Hsp90) off of basal expression promoters and onto heat shock-responsive promoters, led to increased transposable element expression. This effect was amplified by the concurrent delivery of a histone deacetylase inhibitor. We conclude that transposable elements are dysregulated in SLE and there are tissue-specific effects and locus-specific effects. The magnitude of RNAs attributable to transposable elements makes their dysregulation of critical interest in SLE where transposable element RNA complexed with proteins has been shown to drive interferon expression.

Incorporation of CD40 ligand enhances the immunogenicity of tumor­associated calcium signal transducer 2 virus­like particles against lung cancer.

The cell surface glycoprotein Trop­2 is overexpressed in various types of cancer, including in lung cancer, and has recently been used as an effective immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor superfamily member, is a promising immune adjuvant. Human immunodeficiency virus (HIV) gag­based virus­like particles (VLPs) are highly immunogenic, and foreign antigens can be incorporated onto their membrane envelope for cancer vaccine development. In the present study, a HIV gag­based VLP strategy and Bac­to­Bac system were utilized to construct Trop­2, CD40L and gag recombinant baculoviruses, which were then used to infect TN5 cells in order to form Trop­2 VLPs or Trop­2­CD40L VLPs. These VLPs were characterized using transmission electron microscopy and western blot analysis methods. VLPs incorporating murine Trop­2 only or incorporating Trop­2 and CD40L were used to immunize C57BL/6 mice. Immunized mice demonstrated high humoral and cellular immunity responses, whereas the Trop­2­CD40L VLPs led to higher immune responses in comparison with Trop­2 only VLPs. Immunization with Trop­2­CD40L VLPs also reduced tumor growth more effectively compared with Trop­2 VLPs. Furthermore, Trop­2­CD40L VLP immunization increased the survival rate of Lewis tumor­bearing mice more significantly when compared with Trop­2 only VLPs. In conclusion, the present study provided a novel vaccine design by combination of a tumor antigen and an immune adjuvant based on a VLP strategy, which may be potentially applied as an alternative immunotherapeutic option in the treatment of lung cancer.

Acute Massive Pulmonary Thromboembolism Treated by Selective Catheter-Directed Thrombolysis.

BACKGROUND: To evaluate the safety and efficacy of selective catheter-directed thrombolysis (SCDT) in treating acute massive pulmonary thromboembolism (AMPTE). METHODS: Twenty-six AMPTE patients were enrolled between March 2010 and March 2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery thrombus. The thrombolytic regimen included an intraoperative bolus injection of 250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000 IU/kg per (every) 24 hr urokinase for 72 hr postoperatively. Clinical symptoms, shock index (SI), systolic pulmonary artery pressure (sPAP), peripheral arterial partial pressure of oxygen (PaO2), and Miller index (MI) were assessed before and after treatment. RESULTS: The patients included 16 men and 10 women (49.9 ± 18.8 years old; time to onset of 50.2 ± 28.5 hr). After thrombolysis, dyspnea and cough were relieved to varying degrees; chest pain, hemoptysis, and syncope disappeared. Importantly, a clinical success rate of 100% was achieved. All objective indices were improved: SI decreased from 1.74 ± 0.38 before operation to 0.71 ± 0.09 postoperatively (P = 0.00); PaO2 increased from 52.78 ± 6.92 mm Hg to 85.98 ± 5.91 mm Hg (P = 0.00); sPAP was reduced from 65.19 ± 8.22 mm Hg to 34.42 ± 4.05 mm Hg (P = 0.00); MI dropped from 0.69 ± 0.09 to 0.33 ± 0.06 (P = 0.00). Mean total urokinase amounts were 1,298,000 IU for each patient. Postoperative complications included 2 cases of puncture-site hematoma (cured by pressure bandage) and 1 case of gastrointestinal hemorrhage (healed by conservative treatment without blood transfusion). CONCLUSIONS: SCDT may be considered a safe and efficacious treatment for AMPTE.

Surface electromyography based muscle fatigue analysis for stroke patients at different Brunnstrom stages.

Muscle fatigue analysis has been an important topic in sport and rehabilitation medicine due to its role in muscle performance evaluation and pathology investigation. This paper proposes a surface electromyography (sEMG) based muscle fatigue analysis approach which was specifically designed for stroke rehabilitation applications. 14 stroke patients from 5 different Brunnstrom recovery stage groups were involved in the experiment and features including median frequency and mean power frequency were extracted from the collected sEMG samples for investigation. After signal decomposition, the decline of motor unit firing rate of patients from different groups had also been studied. Statistically significant presence of fatigue had been observed in deltoideus medius and extensor digitorum communis of patients at early recovery stages (P<;0.05) and no similar observation had been obtained for patients at later stages (P>0.01). It had also been discovered that the motor unit firing frequency declines with a range positively correlated to the recovery stage during repetitive movements. Based on the experiment result, it can be verified that as the recovery stage increases, the central nervous system's control ability strengthens and the patient motion becomes more stable and resistive to fatigue.