The semantic comparisons of Gene Ontology (GO) annotations provide quantitative ways to compute similarities between genes and gene groups, and have became important basis for many bioinformatics ...analysis approaches. GOSemSim is an R package for semantic similarity computation among GO terms, sets of GO terms, gene products and gene clusters. Four information content (IC)- and a graph-based methods are implemented in the GOSemSim package, multiple species including human, rat, mouse, fly and yeast are also supported. The functions provided by the GOSemSim offer flexibility for applications, and can be easily integrated into high-throughput analysis pipelines. Availability: GOSemSim is released under the GNU General Public License within Bioconductor project, and freely available at http://bioconductor.org/packages/2.6/bioc/html/GOSemSim.html Contact: boxc@bmi.ac.cn; sqwang@bmi.ac.cn Supplementary information: Supplementary information is available at Bioinformatics online.
Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of ...cellular nicotinamide adenine dinucleotide (NAD⁺) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD⁺ precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmdmdx/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD⁺ may reprogram dysfunctional SCs and improve life span in mammals.
Facing the increasingly serious energy and environmental crisis, the development of heteronuclear metal-free double-atom catalysts is a potential strategy to realize efficient catalytic nitrogen ...reduction with low energy consumption and no pollution because it could combine the advantages of flexible active sites in double-atom catalysts while also being pollution-free and have high Faraday efficiency in metal-free catalysts simultaneously. However, according to the existing mechanism, the finite orbits of other nonmetallic atoms, except the boron atom, reduce the possibility of metal-free catalysis and hinder the development of heteronuclear metal-free double-atom catalysts. Herein, we propose a new “capture-backdonation-recapture” mechanism, which skillfully uses the electron capture-backdonation-recapture between boron, the substrate, and other nonmetallic elements to solve the above problems. Based on this mechanism, by means of the first-principle calculations, the material structure, adsorption energy, catalytic activity, and selectivity of 36 catalysts are systematically investigated to evaluate their catalytic performance. B–Si@BP1 and B–Si@BP3 are selected for their good catalytic performance and low limiting potentials of −0.14 and −0.10 V, respectively. Meanwhile, the “capture-backdonation-recapture” mechanism is also verified by analyzing the results of adsorption energy and electron transfer. Our work broadens the ideas and lays the theoretical foundation for the development of heteronuclear metal-free double-atom catalysts in the future.
In this paper, we investigate the coverage and energy consumption control in mobile heterogeneous wireless sensor networks (WSNs). By term heterogeneous, we mean that sensors in the network have ...various sensing radius, which is an inherent property of many applied WSNs. Two sensor deployment schemes are considered-uniform and Poisson schemes. We study the asymptotic coverage under uniform deployment scheme with i.i.d. and 1-D random walk mobility model, respectively. We propose the equivalent sensing radius (ESR) for both cases and derive the critical ESR correspondingly. Our results show that the network performance largely depends on ESR. By controlling ESR, we can always promise the network achieve full coverage, regardless of the total number of sensors or the sensing radius of a single senor under random mobility patterns, which is a much easier and more general way to operate coverage control. Meanwhile, we can operate a tradeoff control between coverage performance and energy consumption by adjusting ESR. We demonstrate that 1-D random walk mobility can decrease the sensing energy consumption under certain delay tolerance, though requires larger ESR. Also, we characterize the role of heterogeneity in coverage and energy performance of WSNs under these two mobility models, and present the discrepancy of the impact of heterogeneity under different models. Under the Poisson deployment scheme, we investigate dynamic k -coverage of WSNs with 2-D random walk mobility model. We present the relation between network coverage and the sensing range, which indicates how coverage varies according to sensing capability. Both k -coverage at an instant and over a time interval are explored and we derive the expectation of fraction of the whole operational region that is k -covered, which also identifies the coverage improvement brought by mobility.
Abstract Over the years, obesity has become more commonplace and has had a substantial impact on several medical specialties, including reproductive medicine. The potential correlation between the ...visceral adiposity index (VAI) and infertility has yet to be determined. Women between the ages of 18 and 45 were included in this cross-sectional study, which was conducted as part of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2020. Three tertiles were used to group VAI levels. Subgroup analysis and weighted binary logistic regression were employed to investigate the independent relationship between VAI and infertility. Smooth curve fitting was used to explore nonlinear relationships. This cross-sectional study followed the criteria of the STROBE guidelines. Of the 1231 participants, 127 were infertile women aged 18–45 years. A higher VAI was associated with a higher prevalence of infertility (OR = 1.22, 95% CI:1.03–1.45), which remained consistent across all subgroups (p > 0.05 for all interactions). We demonstrated a positive nonlinear association between VAI and infertility using a smooth curve fit. A higher visceral adiposity index level is positively correlated with a higher incidence of infertility among women in the United States. Women who are infertile can be identified using the visceral obesity index, and controlling visceral obesity may help lower the chances of becoming infertile.
The index composed of preoperative lymphocytes, albumin, and neutrophils (LANR), a new composite score based on inflammatory response and nutritional status, has been reported to be associated with ...the prognosis of multiple types of cancer, but the role of LANR in the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated.
The data of 142 patients with PDAC who underwent radical resection in the Affiliated Hospital of Jiangnan University from January 2015 to December 2018 were retrospectively analyzed. Receiver Operating Characteristic (ROC) curves were generated to determine the optimal cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting survival. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The optimal cut-off value of LANR was 18.145, and a low preoperative LANR was significantly correlated with the location of the tumor (p = 0.047). Multivariate analysis showed that tumor differentiation degree (HR:2.357, 95%CI:1.388-4.003,p = 0.002), lymph node metastasis (HR:1.755, 95%CI: 1.115-2.763, p = 0.015), TNM stage (HR:4.686, 95%CI: 2.958-7.425, p < 0.001), preoperative cancer antigen 19 - 9 levels (HR:1.001, 95%CI: 1.000-1.001, p < 0.001) and preoperative LANR (HR:0.221, 95%CI: 0.111-0.441, p < 0.001) were independent risk factors for a poor prognosis in patients undergoing radical resection of PDAC.
This study found that preoperative LANR can be used to assess the prognosis of radical resection in patients with PDAC; those with low preoperative LANR had a worse outcome.
The quality of life of people with disabilities is of great significance to social stability and development. Increasing the quality of life among the disabled has become a worldwide topic. This ...study aims to examine the relationship between the big five personality and quality of life and the mediating effects of social support indicators in people with disabilities.
This was a cross-sectional study with 358 people with disabilities (193 women and 165 men). A questionnaire was utilized to measure big five personality, social support, and quality of life variables. Pearson's correlation analysis and structural equation modeling were used to examine the relation among big five personality, social support, and quality of life.
QOL was positively correlated with social support (
= 0.402
< 0.001), extraversion (
= 0.324
< 0.001), agreeableness (
= 0.474
< 0.001), conscientiousness (
= 0.482
< 0.001), and openness (
= 0.498
< 0.001). QOL was negatively correlated with neuroticism (
= -0.186
< 0.001). The mediating effect of social support on the relationship between neuroticism and the quality of life of people with disabilities was not significant. Social support significantly mediated the relationship between extraversion, agreeableness, conscientiousness, openness, and quality of life. Overall, positive personality traits (extraversion, agreeableness, conscientiousness, and openness) in the Big Five Personality of people with disabilities could increase their quality of life by Perceiving social support. But social support could not significantly mediate the relationship between neuroticism and the quality of life of people with disabilities.
These new findings suggest that combining individual factors (personality) and environmental factors (social support) can better improve the quality of life of people with disabilities.
The purpose of this study was to investigate the role of preoperative lymphocytes, albumin, neutrophils, and LANR in the prognosis of patients with stage IB-IIA cervical cancer (CC).
We made a ...retrospective analysis of the clinical information and related materials of 202 patients with stage IB-IIA primary cervical cancer who had undergone a radical hysterectomy in the Department of Gynecology at the Affiliated Hospital of Jiangnan University between January 2017 and December 2018. The definition of LANR was as follows: LANR, lymphocyte × albumin / neutrophil. The receiver operating characteristic curve (ROC) was generated to determine the best cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting recurrence and survival. The Kaplan-Meier method was employed to draw survival curves in our survival analysis. Univariate analysis, multifactorial analysis, and subgroup analysis were used to evaluate the prognostic significance of LANR in overall and progression-free survival.
The median follow-up time of the study was 55 months. In overall survival, the area under the curve for LANR was 0.704 (95% CI: 0.590-0.818, p<0.05). And in progression-free survival, the area under the curve for LANR was 0.745 (95% CI: 0.662-0.828, p<0.05). Univariate and multivariate analyses showed that the value of LANR was associated with both overall survival and progression-free survival (p< 0.05). Kaplan-Meier analysis demonstrated that OS (p< 0.001) and PFS (p< 0.001) in patients with high LANR levels were significantly higher than those with low LANR levels.
Our findings suggested that LANR might serve as a clinically reliable and effective independent prognostic indicator in patients with stage IB-IIA cervical cancer.
Spermidine (SPD) delays age-related pathologies in various organisms. SPD supplementation overcame the impaired immunotherapy against tumors in aged mice by increasing mitochondrial function and ...activating CD8
+
T cells. Treatment of naïve CD8
+
T cells with SPD acutely enhanced fatty acid oxidation. SPD conjugated to beads bound to the mitochondrial trifunctional protein (MTP). In the MTP complex, synthesized and purified from
Escherichia coli
, SPD bound to the α and β subunits of MTP with strong affinity and allosterically enhanced their enzymatic activities. T cell–specific deletion of the MTP α subunit abolished enhancement of programmed cell death protein 1 (PD-1) blockade immunotherapy by SPD, indicating that MTP is required for SPD-dependent T cell activation.
Spermidine fights cancer in aging mice
Abundance of the polyamine spermidine decreases in aging mice, and supplementation can have restorative effects and extend life span. Al-Habsi
et al
. explored whether loss of spermidine might contribute to loss of antitumor immunity in aged mice. Restoration of spermidine concentrations enhanced antitumor responses stimulated by programmed death ligand-1 (PD-L1) monoclonal antibody therapy. Spermidine appeared to directly affect T cell function by increasing fatty acid oxidation. Tagged spermidine bound to components of the mitochondrial trifunctional protein complex, thus increasing fatty acid oxidation and the production of ATP. The authors propose that these effects may contribute to the effects of spermidine in promoting longevity. —LBR
Spermidine helps to restore antitumor immunity in older mice.
INTRODUCTION
In mammals, the power of the immune system decreases with age. This is because of multiple factors, including a decrease in the output and diversity of the antigenic repertoire of T cells caused by thymus involution; changes in the cellular metabolism caused by inflammation; and defective proliferative, differentiation, or survival capacities of the immune cells. Aged individuals frequently suffer from severe infections and cancers, and often the therapies applied, including programmed cell death protein 1 (PD-1) blockade in cancer immunotherapy, are ineffective when compared with results in young patients. A biogenic polyamine, spermidine (SPD), decreases with age, and SPD supplementation was shown to improve or delay several age-related pathologies, including those of the immune system. Among the proposed mechanisms responsible for rejuvenation of the immune system by SPD were enhanced autophagy, translational activity, and mitochondrial metabolism. SPD supplementation has previously been shown to enhance the antitumor immunity in animal models. However, it remains largely unknown how SPD deficiency relates to the T cell immune suppression induced by aging.
RATIONALE
Because CD8
+
T cells are key players in tumor immunity, we investigated how aging would affect the metabolic and functional characteristics of CD8
+
T cells. We asked whether SPD insufficiency could be a factor contributing to nonresponsiveness to PD-1 antibody therapy in aged mice. We sought to characterize the CD8
+
T cell population changes induced by SPD supplementation in aged mice and to identify the molecular mechanisms for the SPD action.
RESULTS
We found that the total and free intracellular concentrations of SPD in CD8
+
T cells from aged mice were about half as much as the concentrations found in young mice. Bioenergetically, aged CD8
+
T cells showed impaired mitochondrial activity with lower oxygen consumption rate, adenosine 5′-triphosphate (ATP) production, and fatty acid oxidation (FAO) activity compared with young CD8
+
T cells.
We show that SPD supplementation enhanced the antitumor activity of PD-1 blockade immunotherapy in aged mice. SPD supplementation proved to also be effective in young mice with tumors unresponsive to single anti–programmed death-ligand 1 (PD-L1) antibody therapy. SPD and anti–PD-L1 antibody combination treatment enhanced the proliferation, cytokine production, and mitochondrial ATP production of CD8
+
T cells in vivo. In vitro, SPD effectively enhanced mitochondrial functions and metabolized palmitate into tricarboxylic acid cycle components within 1 hour, which suggests the possibility of direct SPD binding to mitochondria-related proteins. Biochemical analysis identified SPD binding to mitochondrial trifunctional protein (MTP), which is the central enzyme of fatty acid β-oxidation. MTP is composed of α and β subunits, both of which bind SPD. Several assays using the MTP synthesized and purified from
Escherichia coli
revealed that SPD bound with strong affinity binding affinity (dissociation constant,
K
d
) = 0.1 μM and allosterically enhanced their enzymatic FAO activities. Furthermore, we found that spermine, another polyamine derived from SPD with important cellular protective functions, also directly binds to MTP and competitively inhibits FAO activity of SPD, which suggests the importance of SPD and spermine balance for FAO evaluation in aged cells. T cell–specific deletion of the MTP α subunit abolished enhancement of PD-1 blockade immunotherapy by SPD, indicating that MTP is required for SPD-dependent T cell activation.
CONCLUSION
SPD enhances FAO by directly binding and activating the MTP. SPD supplementation enhances the FAO activity and boosts the mitochondrial activities and cytotoxic functions of CD8
+
T cells. We provide new insights into the properties of SPD that may facilitate the development of strategies to prevent and improve outcomes of age-related immune pathologies and combat unresponsiveness to PD-1 blockade therapy in cancers, regardless of age.
SPD binds to MTP and activates FAO in T cells.
SPD directly activates MTP, which plays a central role in FAO. SPD concentration is decreased in aged T cells, leading to low FAO activity and ATP production compared with those in young T cells. SPD supplementation activates FAO in aged and young T cells, which enhances the efficacy of PD-1 blockade cancer immunotherapy. CoA, coenzyme A; TCA, tricarboxylic acid; ETC, electron transport chain. Figure created by Biorender
Abstract
Background
Endometrial carcinoma (EC) is one of the world’s typical female reproductive tract malignancies, mostly occurring in postmenopausal women. Many reports have confirmed that long ...non-coding RNA SOX21 antisense RNA1 (lncRNA SOX21-AS1) is associated with the progressions of various cancer. However, the mechanism of SOX21-AS1 in EC remains unclear. Our study is intended to probe the mechanisms of SOX21-AS1 on EC progression.
Methods
The CCK-8 assay and colony formation detected cell proliferation. Cell migration and invasion were assessed by transwell analysis. Apoptosis was measured by flow cytometry assay. Bioinformatics software predicted target binding and confirmed using a luciferase reporter analysis.
Results
SOX21-AS1 expression was upregulated in EC tumor tissues and cells. High expression of SOX21-AS1 was associated with poor overall survival. Silencing of SOX21-AS1 restrained cell proliferation, migration, invasion, and increased apoptosis in HEC-1A and Ishikawa cells. Additionally, bioinformatics analysis demonstrated that SOX21-AS1 modulated RAF1 expression by competitively binding to miR-7-5p. Functionally, silencing of RAF1 reversed the functions of miR-7-5p inhibitor in the proliferation, invasion, and apoptosis of HEC-1A/sh-SOX21-AS1 and Ishikawa/sh-SOX21-AS1 cells.
Conclusions
SOX21-AS1 promoted the pathological development of EC by regulating the miR-7-5p/RAF1 pathway. This research may provide a novel target for EC therapy.
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