Sarcoma ecosystems : spatial characterization and prognostic significance

Sarcoma is a highly heterogeneous disease with complex biological activities and unique tumor microenvironments (TME) in distinct subtypes. The limited treatment options and inadequate responses to current therapies necessitate a deeper understanding of sarcoma biology and personalized treatment strategies. Our research comprehensively explores the sarcoma TME through advanced spatial analysis and investigates sarcoma's molecular and genetic profiles through transcriptome and genome sequencing. In paper I, we focused on undifferentiated pleomorphic sarcoma (UPS) using multiplex immunofluorescence (mIF) staining for in-depth spatial analysis of B cell populations and lymphocyte aggregates (LAs). LAs in UPS were found to be associated with longer overall survival (OS) and metastasis-free survival (MFS). Moreover, we unveiled distinct maturation profiles among B cell subsets, indicative of different phenotypes that contribute to functional ecosystems in TME. LA-positive tumors displayed a more well-differentiated B cell profile throughout the entire tumor section, not limited in LA regions. We introduced the B-index, an integrated measurement tool combining B cell abundance and maturity, which demonstrated predictive power for both MFS and OS. Using the TissUUmap tool, we identified B cell desert areas characterized by extremely low B cell infiltration. LA-positive tumors displayed smaller and more fragmented B cell desert areas. In paper II, we performed double immunohistochemistry to study CD11c-positive antigen-presenting cells (APCs) and CD8- positive cells in 177 soft tissue sarcoma (STS) patients. We found that CD11c-CD8 interactions in the TME were associated with improved MFS and OS. Transcriptomic analysis in The Cancer Genome Atlas (TCGA) sarcoma cohort supported the prognostic significance of combining CD11c with CD8, irrespective of FOXP3 levels and in the presence of CD274 (PD-L1). In paper III, we conducted transcriptome and targeted DNA sequencing in 91 synovial sarcomas, identifying three distinct Synovial Sarcoma Clusters (SSCs) mirroring histological subtypes. SSC-I was characterized by high cell proliferation and immune evasion with an unfavorable prognosis. SSC-II was dominated by vascularstromal components and correlated with better outcomes. SSC-III displayed biphasic differentiation, genomic complexity, and immune checkpoint-mediated immune suppression, leading to adverse outcomes, even after a good histological response to neoadjuvant treatment. In paper IV, we analyzed Ewing sarcoma (ES) transcriptome signatures in four previously published cohorts and identified 29 prognostic RNA-binding protein (RBP) genes, from which we constructed and validated an RBP-associated prognostic risk model (RPRM). The RPRM demonstrated stable predictive value for prognosis, with NSUN7 emerging as an independent and favorable prognostic marker. In summary, our research integrates spatial analysis of the sarcoma TME to identify unique immune features and prognostic markers. Moreover, we use transcriptomic and genomic analyses to categorize specific sarcoma types for more detailed survival stratification. This work provides a deeper insight into the sarcoma TME and suggests an improved grouping strategy, aiming to shape the development of personalized immunotherapy in the future

A Research Model Construction of Impact of IT Usage on University Faculty’s Teaching Self-efficacy

Nowadays, the information technology has been widely used in teaching activities, enabling more and more teachers to improve and facilitate their ways of teaching and communicating. However, how does IT usage exert influence on teaching self-efficacy, especially in university classes, still needs to be further studied. Based on Bandura’s self-efficacy theory, and literature review of flipped classroom which is the most representative and latest application scenarios of information technology, we try to identify applicable conceptual dimensions of teaching self-efficacy of university faculty and to construct a research model of influencing mechanism of IT usage on faculty’s teaching self-efficacy. Further study directions are suggested at the end of the research

Analysis of two pheromone-responsive conjugative multiresistance plasmids carrying the novel mobile optrA locus from Enterococcus faecalis

Background: The acquired optrA gene, which encodes a ribosomal protection protein of the ABC-F family, can confer cross-resistance to linezolid and florfenicol, posing a serious therapeutic challenge to both human and veterinary medicine. Purpose: The objective of this study was to investigate the two Enterococcus faecalis (E. faecalis) plasmids for their fine structure, their transferability and the presence of mobile antimicrobial resistance loci. Methods: To elucidate their fine structure, the two plasmids were completely sequenced and the sequences analysed. Besides conjugation experiments, inverse PCR assays were conducted to see whether minicircles are produced from the mobile antimicrobial resistance loci. Results: Two pheromone-responsive conjugative optrA-carrying plasmids from E. faecalis, pE211 and pE508 were identified, which can transfer with frequencies of 2.6 ×10−2 and 3.7 ×10−2 (transconjugant per donor), respectively. In both plasmids, optrA was located on the novel mobile optrA locus with different sizes (12,834 bp in pE211 and 7,561 bp in pE508, respectively), flanked by two copies of IS1216 genes in the same orientation. Inverse PCR revealed that circular forms can be generated, consisting of optrA and one copy of IS1216, indicating they are all active. The 77,562 bp plasmid pE211 also carried Tn558 and a mobile bcrABDR locus, and the 84,468 bp plasmid pE508 also harbored the genes fexA, tet(L), tet(O/W/32/O) and a mobile aac(A)-aph(D) locus. Conclusion: The presence of mobile genetic elements in these plasmids renders them flexible and these elements will aid to the persistence and dissemination of these plasmids among enterococci and potentially also other gram-positive bacteria

PO-302 The Research on the Effects of Resistance Training on the Stress of Skeletal Muscle Endoplasmic Reticulum and Mitochondrial Autophagy in Aging Rats

Objective By establishing a resistance training model, the researchers observed the effects of resistance exercise on the endoplasmic reticulum stress and mitochondrial autophagy-related factors in aging rats and further discussed the physiological mechanism of resistance movement in preventing and delaying senile skeletal muscle decay . Methods 20 adult rats and 20 aged rats were randomly divided into two groups. The adult group was divided into the control Group C and the Sports Group E Group, the elderly group were divided into the control group OC Group and the Sports Group OE Group, 10/group. The eight-week tail-loading ladder training method was used to intervene the suitable resistance training for rats in the exercise group. During this period, rats in the control group did not exercise any training activities and ate normally. The relative expression of PINK1, PARKIN, LC3, PERK/EIF2A and Caspase-12 mRNA in gastrocnemius muscle of rats were detected by quantitative PCR after the experiment. The expression of Pink1/parkin protein in gastrocnemius muscle of rats was detected by Western Blot method. High performance liquid chromatography was performed to detect the ATP production of rat gastrocnemius mitochondria, and the obtained data were collected and analyzed. Results (1) Compared with group C, the expression of PINK1 protein and parkin protein of gastrocnemius muscle in OC Group decreased significantly (p<0.05). PINK1 protein and Parkin protein in OE Group increased significantly (p<0.01) compared with OC Group.(2) Compared with group C, the expression of Pink1mRNA, PARKIN mRNA and Lc3 mRNA in OC group showed a downward trend (p<0.05), and the expression of Pink1 mRNA, PARKIN mRNA and Lc3 mRNA in Group E showed an ascending trend (p<0.01). Compared with OC , the expression of Pink1 mRNA, PARKIN mRNA and Lc3 mRNA in OE group increased and had significant difference (p<0.01).(3) Compared with group C, the expression levels of perk mRNA, eif2a mRNA and Caspase-12 mRNA in the gastrocnemius of rats in Group E were significantly lower (p<0.01), and the expression of perk mRNA in OC Group had a significant upward trend (p<0.05). Compared with OC Group , the expression levels of perk mRNA, eif2a mRNA and Caspase-12 mRNA in OE group showed significant decrease (p<0.01).(4) There was a small increase in mitochondrial ATP production in Group E rats and Group C, but there was no significant difference. The mitochondrial ATP production in Group C was significantly higher than that in OC Group, and had significant difference (p<0.01). After 8 weeks ' training, the mitochondrial function of the OE group was restored to normal, and the ATP production in the OC group increased significantly, there was significant difference (p<0.05). Conclusions The resistance training can improve the function of mitochondria and activate the autophagy, which can improve the abnormality of mitochondria autophagy caused by skeletal muscle decay. Resistance training can reduce the extent of endoplasmic reticulum stress, suggesting that skeletal muscle decay can be slowed down by prolonged exercise

Prevalence of mobile genetic elements and transposase genes in Vibrio alginolyticus from the southern coastal region of China and their role in horizontal gene transfer

Vibrio alginolyticus has high genetic diversity, but little is known about the means by which it has been acquired. In this study, the distributions of mobile genetic elements (MGEs), including integrating conjugative elements (ICEs), superintegron-like cassettes (SICs), insertion sequences (ISs), and two types of transposase genes (valT1 and valT2), in 192 strains of V. alginolyticus were investigated. ICE, SIC, and IS elements, valT1, and valT2 were detected in 8.9 %, 13.0 %, 4.7 %, 9.4 %, and 2.6 % of the strains, respectively. Blast searches and phylogenetic analysis of the acquired sequences of the ICE, SIC, IS elements and transposase genes showed that the corresponding homologues were bacterial and derived from extensive sources. The high prevalences of the se MGEs in V. alginolyticus implied the extensive and frequent exchange of genes with environmental bacteria and that these elements strongly contribute to the genetic and phenotypic diversity of the bacterium. To our knowledge, this is the fi rst report of V. alginolyticus harboring ICE and SIC elements. [Int Microbiol 2012; 15(4): 199-208

Structural Behavior of Thin-Walled Concrete-Filled Steel Tube Used in Cable Tunnel: An Experimental and Numerical Investigation

One steel grid and five thin-walled concrete-filled steel tubes (CTST) used as the supports of tunnel were tested in site for investigating the mechanical behavior. The mechanical influences of thickness, node form, and concrete on CTST were gained and compared with the impacts on steel grid. It is indicated that high antideformation capacity of CTST improved the stability of surrounding rock in short time. The cementitious grouted sleeve connection exhibited superior flexibility when CTST was erected and built. Although the deformation of rock and soil in the tunnel was increasing, good compression resistance was observed by CTST with the new connection type. It was also seen that vault, tube foot, and connections were with larger absolute strain values. The finite element analysis (FEA) was carried out using ABAQUS program. The results were validated by comparison with experimental results. The FE model could be referred by similar projects

Diagnostic value of urine sCD163 levels for sepsis and relevant acute kidney injury: a prospective study

BACKGROUND: Sepsis is a common syndrome in critically ill patients and easily leads to the occurrence of acute kidney injury (AKI), with high mortality rates. This study aimed to investigate the diagnostic value of urine soluble CD163 (sCD163) for identification of sepsis, severity of sepsis, and for secondary AKI, and to assess the patients’ prognosis. METHODS: We enrolled 20 cases with systemic inflammatory response syndrome (SIRS), 40 cases with sepsis (further divided into 17 sepsis cases and 23 severe sepsis cases) admitted to the intensive care unit (ICU), and 20 control cases. Results for urine sCD163 were recorded on the day of admission to the ICU, and AKI occurrence was noted. RESULTS: On the day of ICU admission, the sepsis group exhibited higher levels of urine sCD163 (74.8 ng/ml; range: 47.9-148.3 ng/ml) compared with those in the SIRS group (31.9 ng/ml; 16.8-48.0, P < 0.001). The area under the curve (AUC) was 0.83 (95% confidence interval [CI]: 0.72-0.94, P < 0.001) the sensitivity was 0.83, and the specificity was 0.75 (based on a cut-off point of 43.0 ng/ml). Moreover, the severe sepsis group appeared to have a higher level of sCD163 compared with that in the sepsis group (76.2; 47.2-167.5 ng/ml vs. 74.2; 46.2-131.6 ng/ml), but this was not significant. For 15 patients with AKI, urine sCD163 levels at AKI diagnosis were significantly higher than those of the remaining 35 sepsis patients upon ICU admission (121.0; 74.6-299.1 ng/ml vs. 61.8; 42.8-128.3 ng/ml, P = 0.049). The AUC for urine sCD163 was 0.688 (95% CI: 0.51-0.87, P = 0.049). Sepsis patients with a poor prognosis showed a higher urine sCD163 level at ICU admission (98.6; 50.3-275.6 ng/ml vs. 68.0; 44.8-114.5 ng/ml), but this was not significant. Patients with AKI with a poor prognosis had higher sCD163 levels than those in patients with a better prognosis (205.9; 38.6-766.0 ng/ml vs. 80.9; 74.9-141.0 ng/ml), but this was not significant. CONCLUSIONS: This study shows, for the first time, the potential value of urine sCD163 levels for identifying sepsis and diagnosing AKI, as well as for assessment of patients’ prognosis. TRIAL REGISTRATION: ChiCTR-ONC-1000081

Effects of blood flow restriction training on muscle fitness and cardiovascular risk of obese college students

Purpose: The aim of this study was to investigate the effect of blood flow restriction (BFR) combined with low-intensity resistance training (RT) on cardiovascular risk factors in obese individuals.Methods: Twenty-six male obese college students were recruited and randomly assigned to a control group (CON, n = 8), a low-intensity RT group (RT, n = 9), and a combined BFR training and low-intensity RT group (BFRT, n = 9).Results: The subjects in BFRT group showed significant reductions in body fat percentage and waist-to-hip ratio and a significant increase in lean mass and muscle mass; the peak torque, peak power, and endurance ratio of knee extensors and elbow flexors were significantly upregulated; the root mean square (RMS) for the medial femoral muscle, lateral femoral muscle and biceps significantly increased; the diastolic blood pressure (DBP) showed a significant decrease. The BFRT group also showed significant up-regulations in RMS of the difference between the adjacent R-R intervals (RMSSD), high-frequency power (HF) of parasympathetic modulatory capacity, the standard deviation of R-R intervals (SDNN) of overall heart rate variability (HRV) changes and low-frequency power (LF) of predominantly sympathetic activity. In addition, glycated hemoglobin (HbA1C), insulin resistance index (HOMA-IR) and fasting blood glucose (FBG) were all significantly downregulated in BFRT group. In parallel, low-density lipoprotein (LDL-C) significantly reduced while high-density lipoprotein (HDL-C) significantly increased in BFRT group.Conclusion: BFR combined with low-intensity RT training effectively improved body composition index, increased muscle mass, improved neuromuscular activation, enhanced muscle strength and endurance, which in turn improved abnormal glucolipid metabolism and enhanced cardiac autonomic regulation

Effects of plant diversity and big-sized trees on ecosystem function in a tropical montane evergreen broad-leaved forest

IntroductionScale dependencies play a vital role in defining the biodiversity-ecosystem functioning relationship in forest ecosystems, which varies based on the magnitude of multiple plant diversity attributes, soil properties, and aboveground biomass in forest ecosystems. However, the effects of plant diversity and big-sized trees on the relationship between plant diversity and aboveground biomass across different scales remain unclear in forest ecosystems.MethodsBased on a 30-ha tropical montane evergreen broad-leaved forest dynamics plot in Yunnan province, China, we comparatively analyzed the importance of scale-dependent effects of multiple plant diversity attributes, soil properties, neighborhood competition intensity and aboveground biomass of big-sized trees, as well as stand structural complexity on aboveground biomass of all woody individuals. The aim is therefore to identify the main predictors for sustaining aboveground biomass of all woody individuals, considering multiple biotic and abiotic factors jointly, as well as underlying mechanisms.ResultsOur results suggest that indicators such as species richness and phylogenetic diversity did not strongly contribute to aboveground biomass of all woody individuals with increasing spatial scales, while aboveground biomass of big-sized trees exhibited the greatest contribution to aboveground biomass of all woody individuals. Stand structural complexity, characterized by variances in woody plant diameter at breast height, also contributed more to aboveground biomass of all woody individuals indirectly via neighborhood competition intensity and aboveground biomass of big-sized trees. Contributions of functional dispersion and community-weighted mean of leaf phosphorus concentration to aboveground biomass of all woody individuals became stronger with increasing spatial scales. Neighborhood competition intensity exhibited a negative linear relationship with aboveground biomass of all woody individuals at the smallest scale, but it affected positively aboveground biomass of all woody individuals across spatial scales, likely due to indirect effects via aboveground biomass of big-sized trees.DiscussionBig-sized trees will likely become more important in biodiversity maintenance and ecosystem function management as deforestation and forest degradation

A Hybrid Classification System for Heart Disease Diagnosis Based on the RFRS Method

Heart disease is one of the most common diseases in the world. The objective of this study is to aid the diagnosis of heart disease using a hybrid classification system based on the ReliefF and Rough Set (RFRS) method. The proposed system contains two subsystems: the RFRS feature selection system and a classification system with an ensemble classifier. The first system includes three stages: (i) data discretization, (ii) feature extraction using the ReliefF algorithm, and (iii) feature reduction using the heuristic Rough Set reduction algorithm that we developed. In the second system, an ensemble classifier is proposed based on the C4.5 classifier. The Statlog (Heart) dataset, obtained from the UCI database, was used for experiments. A maximum classification accuracy of 92.59% was achieved according to a jackknife cross-validation scheme. The results demonstrate that the performance of the proposed system is superior to the performances of previously reported classification techniques