Transcriptome analysis method based on differential distribution evaluation.

Identifying differential genes over conditions provides insights into the mechanisms of biological processes and disease progression. Here we present an approach, the Kullback-Leibler divergence-based differential distribution (klDD), which provides a flexible framework for quantifying changes in higher-order statistical information of genes including mean and variance/covariation. The method can well detect subtle differences in gene expression distributions in contrast to mean or variance shifts of the existing methods. In addition to effectively identifying informational genes in terms of differential distribution, klDD can be directly applied to cancer subtyping, single-cell clustering and disease early-warning detection, which were all validated by various benchmark datasets.

Gestational weight trajectory and risk of adverse pregnancy outcomes among women with gestational diabetes mellitus: A retrospective cohort study.

The aim of this study was to explore gestational weight gain (GWG) trajectories and their associations with adverse pregnancy outcomes. A retrospective cohort study including 11,064 women with gestational diabetes mellitus (GDM) was conducted between 2015 and 2019 in China. The latent class trajectory model was used to identify GWG trajectories, and logistic regression was performed to examine odds ratio (OR) of pregnancy outcomes. Three trajectories of GWG were identified in these 11,604 women with GDM. Trajectory 1: 64.02% of women had sustained moderate GWG throughout pregnancy; Trajectory 2: 17.75% of women showed a high initial GWG but followed by a low GWG from the third trimester until delivery; Trajectory 3: 18.23% had low initial GWG but followed by drastic GWG from the second trimester until delivery. Compared with pregnant women with Trajectory 1, women with Trajectory 2 had a higher risk of large for gestational age (adjusted odds ratio [AOR]: 1.29, 95% confidence interval [CI]: 1.12-1.48) but at a lower risk of having hypertensive disorders of pregnancy (AOR: 0.76, 95% CI: 0.57-0.96). Women in Trajectory 3 were more likely to develop small for gestational age (AOR: 2.12, 95% CI: 1.62-2.78), low birthweight (AOR: 1.49, 95% CI: 1.07-2.08), preterm birth (AOR: 1.28, 95% CI: 1.05-1.63), caesarean section (AOR: 1.26, 95% CI: 1.112-1.42) and hypertensive disorders of pregnancy (AOR: 2.24, 95% CI: 1.82-2.76). The association of GWG trajectory with adverse pregnancy outcomes differs across prepregnancy body mass index and GWG categories. Women with a slow initial GWG but followed by drastic GWG had higher risks of adverse pregnancy outcomes. Early clinical recognition of poor GWG trajectory will contribute to early intervention in high-risk groups to minimise adverse outcomes.

Disease characterization using a partial correlation-based sample-specific network.

A single-sample network (SSN) is a biological molecular network constructed from single-sample data given a reference dataset and can provide insights into the mechanisms of individual diseases and aid in the development of personalized medicine. In this study, we proposed a computational method, a partial correlation-based single-sample network (P-SSN), which not only infers a network from each single-sample data given a reference dataset but also retains the direct interactions by excluding indirect interactions (https://github.com/hyhRise/P-SSN). By applying P-SSN to analyze tumor data from the Cancer Genome Atlas and single cell data, we validated the effectiveness of P-SSN in predicting driver mutation genes (DMGs), producing network distance, identifying subtypes and further classifying single cells. In particular, P-SSN is highly effective in predicting DMGs based on single-sample data. P-SSN is also efficient for subtyping complex diseases and for clustering single cells by introducing network distance between any two samples.

Vitamin D promotes epithelial tissue repair and host defense responses against influenza H1N1 virus and Staphylococcus aureus infections.

BACKGROUND: Early studies indicated that vitamin D (VD) exerted pleiotropic extra-skeletal effects in the airway, but the definite linkage between VD deficiency and airway host responses remains unclear. METHODS: 142 cases of clinical data from Department of Otolaryngology, the Seventh Affiliated Hospital of Sun Yat-sen University, were collected to characterize the relationship between VD deficiency and chronic rhinosinusitis (CRS). Based on the clinical observations, 2.5-D airway epithelial organoids cultured at the air-liquid interface (ALI) were used to simulate the effects of VD treatment in the development of airway epithelium and the modulation of the host responses against influenza H1N1 virus (representing viral infections) and Staphylococcus aureus (representing bacterial infections) infections in the airway. The intrinsic mechanisms of VD deficiency underlying epithelial remodeling were mapped by transcriptomic as well as proteomic analyses. RESULTS: In this study we observed prevailing VD deficiency among inpatients suffering from CRS, a common disease predominantly characterized by epithelial impairment and remodeling. Relative to control organoids cultured without VD, long-term incubation with VD accelerated basal cell proliferation during nasal epithelial development. Under infectious conditions, VD treatment protected the organoids against influenza H1N1 virus and Staphylococcus aureus invasions by reinforcing the respiratory host defenses, including upregulation of LL37, suppression (or inhibition) of proinflammatory cytokines, strengthening of epithelial integrity, and mucociliary clearance. In silico analysis of transcriptomics and proteomics suggested that VD modulated the epithelial development and remodeling, involving epithelial cell proliferation/differentiation, epithelial-mesenchymal transition (EMT), and cytokine signaling in the immune system, as well as responses to microbe, cell junction organization, and extracellular matrix organization via PTEN signaling, independent of TGF-ß signaling. CONCLUSIONS: Our findings emphasize the importance of managing VD deficiency in clinical settings for the sake of alleviating pathological epithelial remodeling. Vitamin D promotes epithelial tissue repair and host defense responses against influenza H1N1 and Staphylococcus aureus infections.

Correlation between bacterial diversity and flavor substances in Longgang soy sauce.

Longgang soy sauce is one of the traditional fermented condiments in China, but its bacterial community succession and its unique flavor development during the fermentation process are not well-investigated. This study evaluated the bacterial diversity, flavor changes, and their correlation during the fermentation of Longgang soy sauce. The results showed that Weissella was the dominant bacterial genus in the fermentation stage of sauce fermented grains. In the first 31 days of the moromi fermentation stage, a variety of bacterial genera such as Weissella, Halomonas, Bacteroides, Pseudomonas, and Tetragenococcus were the dominant bacteria. Our results showed that these bacteria have a significantly positive correlation with phenylethyl alcohol, ethyl acetate, and 3-methyl-1-butanol. As the fermentation progressed, a flora structure with Halomonas as the main bacterial genus was formed. This genus exhibited a significantly positive and positive correlation with 1-octanol, ethyl palmitate, heptanol, and 2-nonanol, which are the unique flavor components of Longgang soy sauce.

Transcriptome analysis revealed that short-term stress in Blattella germanica to ß-cypermethrin can reshape the phenotype of resistance adaptation.

Previous studies on insect resistance have primarily focused on resistance monitoring and the molecular mechanisms involved, while overlooking the process of phenotype formation induced by insecticide stress. In this study, we compared the expression profiles of a beta-cypermethrin (ß-CYP) resistant strain (R) and a susceptible strain (S) of Blattella germanica after ß-CYP induction using transcriptome sequencing. In the short-term stress experiment, we identified a total of 792 and 622 differentially expressed genes (DEGs) in the S and R strains. Additionally, 893 DEGs were identified in the long-term adaptation experiment. To validate the RNA-Seq data, we performed qRT-PCR on eleven selected DEGs, and the results were consistent with the transcriptome sequencing data. These DEGs exhibited down-regulation in the short-term stress group and up-regulation in the long-term adaptation group. Among the validated DEGs, CUO8 and Cyp4g19 were identified and subjected to knockdown using RNA interference. Subsequent insecticide bioassays revealed that the mortality rate of cockroaches treated with ß-CYP increased by 69.3% and 66.7% after silencing the CUO8 and Cyp4g19 genes (P<0.05). Furthermore, the silencing of CUO8 resulted in a significant thinning of the cuticle by 59.3% and 53.4% (P<0.05), as observed through transmission electron microscopy and eosin staining, in the S and R strains, respectively. Overall, our findings demonstrate that the phenotypic plasticity in response to short-term stress can reshape the adaptive mechanisms of genetic variation during prolonged exposure to insecticides. And the identified resistance-related genes, CUO8 and Cyp4g19, could serve as potential targets for controlling these pest populations.

Industrial air pollution and low birth weight in New Mexico, USA.

In recent decades, the low birth weight (LBW) rate in New Mexico has consistently exceeded the Unites States average. Maternal exposure to air pollution during pregnancy may be a significant contributor to LBW in offspring. This study investigated the links between maternal residential exposure to air pollution from industrial sources and the risk of LBW in offspring. The analysis included 22,375 LBW cases and 233,340 controls. It focused on 14 common chemicals listed in the Toxic Release Inventory (TRI) and monitoring datasets, which have abundant monitoring samples. The Emission Weighted Proximity Model (EWPM) was used to calculate maternal air pollution exposure intensity. Adjusted odds ratios (adjORs) were calculated using binary logistic regressions to examine the association between maternal residential air pollution exposure and LBW, while controlling for potential confounders, such as the maternal age, race/ethnicity, gestational age, prenatal care, education level, consumption of alcohol during pregnancy, public health regions, child's sex, and the year of birth. Multiple comparison correction was applied using the False Discovery Rate approach. The results showed that maternal residential exposure to 1,2,4-trimethylbenzene, benzene, chlorine, ethylbenzene, and styrene had significant positive associations with LBW in offspring, with adjusted odds ratios ranging from 1.10 to 1.13. These five chemicals remained as significant risk factors after dividing the estimated exposure intensities into four categories. In addition, significant linear trends were found between LBW and maternal exposure to each of the five identified chemicals. Furthermore, 1,2,4-trimethylbenzene was identified as a risk factor to LBW for the first time. The findings of this study should be confirmed through additional epidemiological, biological, and toxicological studies.

A pruned feed-forward neural network (pruned-FNN) approach to measure air pollution exposure.

Environmental epidemiology studies require accurate estimations of exposure intensities to air pollution. The process from air pollutant emission to individual exposure is however complex and nonlinear, which poses significant modeling challenges. This study aims to develop an exposure assessment model that can strike a balance between accuracy, complexity, and usability. In this regard, neural networks offer one possible approach. This study employed a custom-designed pruned feed-forward neural network (pruned-FNN) approach to calculate the air pollution exposure index based on emission time and rates, terrain factors, meteorological conditions, and proximity measurements. The model's performance was evaluated by cross-validating the estimated exposure indexes with ground-based monitoring records. The pruned FNN can predict pollution exposure indexes (PEIs) that are highly and stably correlated with the monitored air pollutant concentrations (Spearman's rank correlation coefficients for tenfold cross-validation (mean ± standard deviation: 0.906 ± 0.028) and for random cross-validation (0.913 ± 0.024)). The predicted values are also close to the ground truth in most cases (95.5% of the predicted PEIs have relative errors smaller than 10%) when the training datasets are sufficiently large and well-covered. The pruned-FNN method can make accurate exposure estimations using a flexible number of variables and less extensive data in a less money/time-consuming manner. Compared to other exposure assessment models, the pruned FNN is an appropriate and effective approach for exposure assessment that covers a large geographic area over a long period of time.

Identifying network biomarkers of cancer by sample-specific differential network.

Abundant datasets generated from various big science projects on diseases have presented great challenges and opportunities, which contributed to unfolding the complexity of diseases. The discovery of disease-associated molecular networks for each individual plays an important role in personalized therapy and precision treatment of cancer-based on the reference networks. However, there are no effective ways to distinguish the consistency of different reference networks. In this study, we developed a statistical method, i.e. a sample-specific differential network (SSDN), to construct and analyze such networks based on gene expression of a single sample against a reference dataset. We proved that the SSDN is structurally consistent even with different reference datasets if the reference dataset can follow certain conditions. The SSDN also can be used to identify patient-specific disease modules or network biomarkers as well as predict the potential driver genes of a tumor sample.

Relationship between flavor compounds and changes of microbial community in the solid fermented vinegar.

The relationship between volatile compounds of vinegar and microorganisms is not clear, especially pyrazine, a trace component. In order to reveal their potential relationship, high throughput sequencing, solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) and Spearman's correlation analysis were used. Results showed that Acetobacter and Lactobacillus with opposite abundance trends were the predominant bacteria, and the total abundance of them exceeds 98%, while the predominant fungal genera were Aspergillus and Malassezia, their highest abundances are 75.4% and 81.5%, respectively. In the whole process of microbial community succession, 6 pyrazines were detected including trimethylpyrazine and tetramethylpyrazine, etc., and Spearman's correlation analysis showed that they were positively correlated with the presence of Vibrionimonas, Paraburkholderia, Paucibacter, Komagataeibacter, Acinetobacter, and Slinibacter. In general, this study further revealed more species related to pyrazines, it will be helpful to understand the formation of pyrazines and promote the improvement of vinegar quality.

Isolation of lipopeptide antibiotics from Bacillus siamensis: a potential biocontrol agent for Fusarium graminearum.

Fusarium head blight (FHB), a destructive fungal disease that can cause damage to various crops and reduce yield and quality, is primarily caused by several species of the soil-borne fungal genus Fusarium, which produce mycotoxins that contaminate grains and may cause various severe chronic diseases in humans and livestock. In recent years, Bacillus spp. have been reported to be good producers of antifungal antibiotics against FHB. This study aimed to explore the potential role of a newly identified Bacillus strain, designated as CU-XJ-9, against FHB. This strain, which was isolated from traditional Chinese fermented food, was identified as Bacillus siamensis and confirmed to produce lipopeptide biosurfactants, which according to the analysis by quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS/MS) may belong to the iturin lipopeptide family. At 100 µg/mL, the isolated antifungal compounds completely inhibited conidial germination. Observation of the effects of the isolated antifungal compounds on the mycelia of F. graminearum by scanning electron microscopy revealed obvious nodes in the middle of the mycelia and destroyed mycelial structures, and these changes became more pronounced with increasing dose. Overall, this study provides important information regarding the ability of Bacillus siamensis to produce lipopeptide biosurfactants, which showed significant antagonistic activity against F. graminearum.

2-Keto-D-gluconic acid and prodigiosin producing by a Serratia marcescens.

Microbial fermentation has become the main method to produce target compound. In this study, a 2-Keto-D-gluconic acid (2-KGA) producing mutant strain was obtained by mutation with rational screening methods. Meanwhile, prodigiosin was produced when the nitrogen source in the medium was changed to peptone and its fermentation conditions were evaluated to achieve high-efficient accumulation. The mutant strain SDSPY-136 was firstly identified as Serratia marcescens by morphological observation and 16S rDNA sequencing. The 2-KGA synthetic capacity of S. marcescens SDSPY-136 was evaluated by shake fermentation with 110 g/L glucose as substrates. For fermentation, 2-KGA yield, conversation rate and purity of SDSPY-136 reached 104.60 g/L, 95.10%, 99.11% in 72 h. The red pigment was extracted from the fermentation broth using acidic methanol and identified as prodigiosin by FT-IR. The optimal conditions were as follows: glycerol 20 g/L, peptone 20 g/L, MgSO415 g/L, pH 6.0, a 2% (v/v) inoculum, 30 °C and 200 rpm of shaking culture. Eventually, prodigiosin reached a yield of 9.89 g/Lafter shake culturing for 50 h under this condition. The mutant S. marcescens SDSPY-136 was shown to be promising for 2-KGA and prodigiosin production and a suitable object for prodigiosin metabolism research of S. marcescens.

Maternal preconception and first trimester exposure to PM10 and the risk of oral clefts in offspring: a population-based, case-control study.

BACKGROUND: Current literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC). METHODS: We conducted a case-control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP). RESULTS: Maternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings. CONCLUSIONS: Our study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

Association between maternal exposure to PM10 and polydactyly and syndactyly: A population-based case-control study in Liaoning province, China.

BACKGROUND: The number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear. OBJECTIVES: To evaluate associations between preconception and first-trimester PM10 exposure and polydactyly and syndactyly in a population-based case-control study. METHODS: Polydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: PM10 exposure was positively associated with the risks of polydactyly (preconception: aORT3 vs. T1 = 1.95, 95% CI 1.56-2.45, aOR = 1.06, 95% CI 1.01-1.10 [per 10-µg/m3 increment]; first-trimester: aORT3 vs. T1 = 2.51, 95% CI 2.00-3.15) and syndactyly (preconception: aORT3 vs. T1 = 2.86, 95% CI 1.98-4.13, aOR = 1.11, 95% CI 1.03-1.20 [per 10-µg/m3 increment]; first-trimester: aORT3 vs. T1 = 3.10, 95% CI 2.11-4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups. CONCLUSION: Our study suggest that preconception and first-trimester PM10 exposures are related to increased risks of polydactyly and syndactyly.

Maternal exposure to ambient particulate matter 10 µm or less in diameter before and after pregnancy, and anencephaly risk: A population-based case-control study in China.

BACKGROUND: There is no epidemiological evidence on the effects of maternal exposure to ambient particulate matter 10 µm or less in diameter (PM10) and anencephaly risk in offspring. METHODS: We conducted a population-based case-control study in Liaoning Province, China. The case group consisted of 663 cases with anencephaly and the control group consisted of 7950 healthy infants from the Maternal and Child Health Certificate Registry of Liaoning Province that were born between 2010 and 2015. Daily PM10 concentrations were obtained from 77 monitoring stations located within the study area. A multivariable logistic regression model was established to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Maternal PM10 exposure was significantly associated with an increased risk of anencephaly at three months before conception (highest versus lowest tertile: OR = 1.74, 95% CI: 1.29-2.34; per 10 µg/m3 increment: OR = 1.13, 95% CI: 1.06-1.20) and three months after conception (highest versus lowest tertile: OR = 1.93, 95% CI: 1.44-2.60; per 10 µg/m3 increment: OR = 1.01, 95% CI: 0.95-1.08). The evaluation of shorter exposure windows revealed similar associations for PM10 exposure from the third month before pregnancy to the third month after pregnancy. CONCLUSIONS: Maternal PM10 exposure is positively associated with anencephaly risk during the critical period of neural system development.

Isolation of an anti-entomopathogenic fungal protein secreted from Pseudomonas aeruginosa BGf-2: An intestinal bacteriam of Blattella germanica (L.).

A bacterial strain (BGf-2) with anti-Beauveria bassiana activity was obtained from the feces of Blattella germanica (L.) and identified as Pseudomonas aeruginosa based on biochemical tests and 16S rRNA sequence analysis. An antifungal protein (A0A0H2ZK06) was purified with Sephadex G-100 column and DEAE-sepharose Fast Flowanion exchange from sterile BGf-2 fermentation liquid. Based on MALDI-TOF MS analysis and protein model building, A0A0H2ZK06 showed homology with Pyrrolidone carboxyl peptidases (pcps). Fermentation liquid and antifungal proteins not only reduced the B. bassiana conidial germination rate but also inhibited hyphal growth. A per os test showed that the mortality of cockroaches decreased after treatment with BGf-2 suspension compared with control. We hypothesized that gut microbes with antifungal activity might play an important role in protect cockroaches from pathogenic fungi.

Ovarian morphological features and proteome reveal fecundity fitness disadvantages in ß-cypermethrin-resistant strains of Blattella germanica (L.) (Blattodea: Blattellidae).

To evaluate whether the development of ß-cypermethrin resistance in Blattella germanica (L.) (Blattaria: Blattellidae) affects the fecundity fitness of this insect and to determine the underlying mechanism, we compared fecundity differences between ß-cypermethrin-resistant (R) and sensitive (S) strains of B. germanica, observed the physiological structural changes of ovaries from an visual perspective, and analyzed differences in the ovarian proteome using proteomic methods. The results showed that, compared with the S strain of B. germanica, the R strain of B. germanica had a significantly higher ootheca shedding rate, a significantly lower number of hatched and surviving nymphs, a significantly higher female proportion in the population and defective ovarian development. Ovarian proteomic analysis showed a total of 64 differentially expressed proteins in the R strain, including 18 upregulated proteins and 46 downregulated proteins. Twenty-four significantly differentially expressed proteins were further studied, and 14 were successfully identified, which were mainly classified into the following categories: immunity-related proteins, development-related proteins, structural proteins, energy metabolism-related proteins and proteins with unknown functions. The differential expression of these proteins reflects the overall changes in cell structure and metabolism associated with ß-cypermethrin resistance and explains the possible molecular mechanism of fecundity fitness disadvantages. In summary, ß-cypermethrin resistance can cause fecundity fitness disadvantages in B. germanica. The metabolic deviations needed to overcome the adverse effects of insecticides may result in an energy exchange that affects energy allocation and, ultimately, the basic needs of the insect. The fitness cost due to insecticide resistance is critical to the delay of the evolution of resistance.

Efficacy and Safety of a Novel Catheter for Transradial Cerebral Angiography.

BACKGROUND: The goal of this study is to evaluate the safety and efficacy of a novel catheter for right radial artery approach cerebral angiography. METHODS: Patients from the Neurology Department of The Second Affiliated Hospital of Guangxi Traditional Chinese Medical University who underwent diagnostic cerebral angiography of either the left vertebral artery dominant type or balanced type were enrolled in this study. RESULTS: A total of 167 patients were treated between February 2016 and December 2017, of whom 44 were excluded based on study exclusion criteria and 123 were enrolled in the present analysis. Bilateral subclavian artery catheterization and bilateral common carotid artery catheterization were conducted successfully in all 123 patients. The success rate of selective catheterization of the left vertebral artery was 87.8% (108/123). The success rate of selective catheterization of the right vertebral artery using the novel catheter was 89.0% (73/82). The average fluoroscopy time was 6.5 ± 3.4 min, the average operation duration was 47 ± 3.7 (range 50-90) min, and the average dosage of contrast agent was 112.3 ± 8.1 mL. One patient exhibited an absence of pulse in the punctual radial artery after the removal of the arterial compression band, but there was no evidence of ischemia of the distal hand. One patient who was undergoing dual anti-platelet drug treatment suffered from bleeding at the puncture point when deflated for 2 hr after operation; this patient was re-pressurized and re-timed. CONCLUSIONS: This novel catheter improved the success rate of selective left vertebral artery catheterization, and allowed for simplification of the relevant surgical steps. The controllability of this novel catheter was satisfactory, and its associated surgical risk was found to be low.

Psychological resilience of women after breast cancer surgery: a cross-sectional study of associated influencing factors.

The psychological resilience (PR) of postoperative patients is found relatively low in clinical work. We recruited 220 postoperative women with breast cancer to survey PR of them and the influencing factors. General demographic data and physical exercise status were collected by questionnaire, clinical characteristics data were obtained from medical records. Measures comprised the Chinese version of the Connor and Davidson Resilience Scale (CD-RISC), General Self-Efficacy Scale (GSES), Family Hardiness Index (FHI) and Social Support Rate Scale (SSRS). The mean (±SD) PR score in women after breast cancer surgery was 65.18 ± 13.16. Clinical stage of breast cancer, courses of adjuvant therapy and physical exercise status affected PR level significantly. PR level was positively correlated with total GSES, FHI, and SSRS scores (r = 0.291, 0.378, 0.418, all P < 0.001); dimensions of FHI; and dimensions of SSRS. On multiple regression analysis, clinical stage of breast cancer and courses of adjuvant therapy negatively, but postoperative physical exercise status, commitment, control and social subjective support positively contributed to PR significantly. Psychological resilience of women after breast cancer surgery is relatively low. Moderate physical exercise, self-efficacy, family hardiness, and social support affect PR positively, promoting disease rehabilitation and improving the quality of life.

NMDA receptor activation inhibits the antifibrotic effect of BM-MSCs on bleomycin-induced pulmonary fibrosis.

Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-ß1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.