Genome-wide analysis of the SWEET gene family in Hemerocallis citrina and functional characterization of HcSWEET4a in response to salt stress.

Sugars will be eventually effluxed transporters (SWEETs) have been confirmed to play diverse physiological roles in plant growth, development and stress response. However, the characteristics and functions of the SWEET genes in Hemerocallis citrina remain unclear and poorly elucidated. In this study, the whole genome of Hemerocallis citrina was utilized to conduct bioinformatics analysis and a total of 19 HcSWEET genes were successfully identified. Analysis of the physicochemical properties indicated dominant differences among these HcSWEETs. A phylogenetic analysis revealed that HcSWEET proteins can be divided into 4 clades ranging from Clade I to IV, where proteins within the same clade exhibited shared conserved motifs and gene structures. Five to six exons were contained in the majority of HcSWEET genes, which were unevenly distributed across 11 chromosomes. The gene duplication analysis showed the presence of 4 gene pairs. Comparative syntenic maps revealed that the HcSWEET gene family might present more closed homology in monocotyledons than dicotyledons. Cis-acting element analysis of HcSWEET genes indicated key responsiveness to various hormones, light, and stresses. Additionally, transcriptome sequencing analysis suggested that most HcSWEET genes had a relatively higher expression in roots, and HcSWEET4a was significantly up-regulated under salt stress. Overexpression further verified the possibility that HcSWEET4a was involved in response to salt stress, which provides novel insights and facilitates in-depth studies of the functional analysis of HcSWEETs in resistance to abiotic stress.

Boosting Bulk Oxygen Transport with Accessible Electrode Nanostructure in Low Pt Loading PEMFCs.

Despite the high potential for reducing carbon emissions and contributing to the future of energy utilization, polymer electrolyte membrane fuel cells (PEMFCs) face challenges such as high costs and sluggish oxygen transport in cathode catalyst layers (CCLs). In this study, the impact of pore size distribution on bulk oxygen transport behavior is explored by introducing nano calcium carbonate of varying particle sizes for pore-forming. Physicochemical characterizations for are employed to examine the electrode structure, while in situ electrochemical measurements are used to scrutinize bulk oxygen transport resistance, effective oxygen diffusivity ( D O 2 eff $D_{{{\mathrm{O}}}_2}^{{\mathrm{eff}}}$ ) and fuel cell performance. Additionally, the CCLs are constructed with aid of Lattice Boltzmann method (LBM) simulations and D O 2 eff $D_{{{\mathrm{O}}}_2}^{{\mathrm{eff}}}$ for CCLs with different pore size distribution are calculated. The findings reveal that D O 2 eff $D_{{{\mathrm{O}}}_2}^{{\mathrm{eff}}}$ initially increases and then decreases as the most probable pore size increases. A "sphere-pipe" model is proposed to describe practical bulk oxygen transport in CCLs, highlighting the significant role of not only the pore size of secondary pores but also the number of primary pores in bulk oxygen transport.

Ethanol responsive lnc171 promotes migration and invasion of HCC cells via mir-873-5p/ZEB1 axis.

BACKGROUNDS: Long nonconding RNAs (lncRNAs) have been found to be a vital regulatory factor in the development process of human cancer, and could regarded as diagnostic or prognostic biomarkers for human cancers. Here, we aim to confirm the expression and molecular mechanism of RP11-171K16.5 (lnc171) in hepatocellular carcinoma (HCC). METHODS: Screening of differentially expressed lncRNAs by RNA sequencing. Expression level of gene was studied by quantitative real-time PCR (qRT-PCR). The effects of lnc171, mir-873-5p, and ethanol on migration and invasion activity of cells were studied used transwell assay, and luciferase reporter assay was used to confirm the binding site. RESULTS: RNA sequencing showed that lnc171 was markedly up-regulated in HCC. siRNA-mediated knockdown of lnc171 repressed the migration and invasion ability of HCC cells. Bioinformatic analysis, dual luciferase reporter assay, and qRT-PCR indicated that lnc171 interacted with mir-873-5p in HCC cells, and Zin-finger E-box binding homeobox (ZEB1) was a downstream target gene of mir-873-5p. In addition, lnc171 could enhance migration and invasion ability of HCC cells by up-regulating ZEB1 via sponging mir-873-5p. More interestingly, ethanol stimulation could up-regulate the increase of lnc171, thereby regulating the expression of competing endogenous RNA (ceRNA) network factors which lnc171 participated in HCC cells. CONCLUSIONS: Our date demonstrates that lnc171 was a responsive factor of ethanol, and plays a vital role in development of HCC via binding of mir-873-5p.

The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts.

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.

Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study.

BACKGROUND: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. METHODS: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. RESULTS: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. CONCLUSION: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.

Effect of acceptance and commitment therapy for depressive disorders: a meta-analysis.

OBJECTIVE: To systematically evaluate the effect of Acceptance and Commitment Therapy (ACT) on depressive disorders. METHODS: The electronic databases of Web of Science Core Collection, Pubmed, EMBASE, Cochrane Library, PsycInfo, CNKI, Wanfang and Weipu were used to select relevant publications. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. RevMan5.4 was used for meta-analysis. RESULTS: 11 studies with a total of 962 patients were included. Random-effects model analysis showed that ACT could effectively reduce the level of depressive symptoms in patients with depressive disorders (SMD = - 1.05, 95% CI: - 1.43-- 0.66, P < 0.00001), improve psychological flexibility (MD = 4.84, 95% CI: 2.70-6.97, P < 0.00001), and have good maintenance effect (SMD = - 0.70, 95% CI: - 1.15-- 0.25, P = 0.002). All differences were statistically significant. CONCLUSIONS: ACT not only improves depressive symptoms and psychological flexibility, but also has a good maintenance effect, and it is particularly effective in Chinese patients. Large randomized controlled trials are needed to validate the findings from this meta-analysis.

Aspartate ß-Hydroxylase Serves as a Prognostic Biomarker for Neoadjuvant Chemotherapy in Gastric Cancer.

Neoadjuvant chemotherapy (NACT) has been established as being an effective treatment for advanced gastric cancer (GC), while the predictive biomarker of NACT efficacy remains under investigation. Aspartate ß-hydroxylase (ASPH) represents an attractive target which is a highly conserved transmembrane enzyme overexpressed in human GC, and participates in the malignant transformation by promoting tumor cell motility. Here, we evaluated the expression of ASPH by immunohistochemistry in 350 GC tissues (including samples for NACT) and found that ASPH expression was higher in patients undergoing NACT compared with patients without NACT pre-operation. The OS and PFS time of ASPH-intensely positive patients was significantly shorter than that of the negative patients in the NACT group, while the difference was not significant in patients without NACT. We showed that ASPH knockout enhanced the inhibitory effects of chemotherapeutic drugs on the cell proliferation, migration, and invasion in vitro and suppressed tumor progression in vivo. Co-immunoprecipitation revealed that ASPH might interact with LAPTM4B to perform chemotherapeutic drug resistance. Our results suggested that ASPH might serve as a candidate biomarker to predict prognosis and a novel therapeutic target for gastric cancer patients treated with neoadjuvant chemotherapy.

Inhibition of exosome release augments neuroinflammation following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe stroke subtype without effective pharmacological treatment. Following ICH, peripheral leukocytes infiltrate into the brain and contribute to neuroinflammation and brain edema. However, the intercellular machinery controlling the initiation and propagation of leukocyte infiltration remains elusive. Exosomes are small extracellular vesicles released from donor cells and bridge intercellular communication. In this study, we investigated the effects of inhibition of exosome release on neuroinflammation and ICH injury. Using a mouse model of ICH induced by collagenase injection, we found that ICH induced an increase of exosome level in the brain. Inhibition of exosome release using GW4869 augmented neurological deficits and brain edema after ICH. The exacerbation of ICH injury was accompanied by increased barrier disruption and brain infiltration of leukocytes. The detrimental effects of GW4869 were ablated in ICH mice receiving antibody depletion of Gr-1+ myeloid cells. Extracted exosomes from the ICH brains suppressed the production of inflammatory factors by splenocytes. Additionally, exosomes extracted from brain tissues of donor ICH mice reduced ICH injury in recipient mice. These results demonstrate that inhibition of exosome release augments neuroinflammation and ICH injury. The impact of exosomes released from the ICH brain on the immune system deserves further investigation.

The relationship between negative life events and non-suicidal self-injury (NSSI) among Chinese junior high school students: the mediating role of emotions.

BACKGROUND: Adolescent non-suicidal self-injury (NSSI) is common and adolescence is the most common period of first self-injury, and the occurrence of NSSI is influenced by negative life events and emotional symptoms. The mediating role of emotional symptoms in the interaction between negative life events and NSSI has not been carefully investigated yet. METHODS: For middle school students in three schools in a Chinese province, the Adolescents Self-Harm Scale was used to investigate NSSI, the Adolescent Self-Rating Life Events Check List was used to investigate adolescent negative life events, and the Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to assess their emotional symptoms. After the description of general data and the test for differences between groups, the relationship between negative life events, emotional symptoms and NSSI was analyzed using Pearson correlation analysis. Structural equation modeling was used to analyze the mediating role of emotions in negative life events and NSSI. RESULTS: A total of 2376 junior high school students completed this survey, which revealed an annual NSSI prevalence of 37.1% (n = 881) and a higher prevalence of NSSI among girls and rural adolescents. Among adolescents who developed NSSI, 67.4% (N = 594) used multiple means of self-injury. The most common means of self-injury was hair pulling (51.0%), and the most common NSSI purpose and external factors/events were venting bad emotions or feelings (57.5%) and poor academic performance (44.9%), respectively. Negative life events, emotional symptoms and NSSI were positively associated (P < 0.05). Structural equation modeling with negative life events, emotional symptoms and NSSI as variables showed that the model-fit index matched the data well, with RMSEA = 0.073, AGFI = 0.945, GFI = 0.980, CFI = 0.985, NFI = 0.982, TLI = 0.968, IFI = 0.985, and negative life events, emotional symptoms (anxiety, depression) and NSSI all had direct effects with standardized path coefficients of 0.16, 0.19, and 0.23, respectively, with negative life events playing an indirect role in NSSI through emotional symptoms and emotional symptoms playing an incomplete mediating role in negative life events and NSSI. CONCLUSION: The prevalence of NSSI was higher among Chinese junior high school students. Both negative life events and emotional symptoms were direct risk factors for NSSI. In addition, negative life events were also indirect risk factors for NSSI, and emotional symptoms played an incomplete mediating role in the relationship between the effects of negative life events and NSSI. This indicates that the combination of reducing the frequency of negative life events while maintaining individual emotional stability during adolescent development can effectively reduce the prevalence of NSSI in adolescents.

Genome-wide identification of CLE gene family and their potential roles in bolting and fruit bearing in cucumber (Cucumis sativus L.).

BACKGROUND: Signal peptides are essential for plant growth and development. In plants, biological processes including cell-cell communication, cellular proliferation and differentiation, cellular determination of self-incompatibility, and defensive responses, all depend heavily on peptide-signaling networks such as CLE (CLAVATA3/Embryo surrounding region-related). The CLEs are indispensable in different periods of plant growth and development, especially in maintaining the balance between proliferation and differentiation of stem cells in various meristematic tissues. The working system of CLE genes in cucumber, an important economical vegetable (Cucumis sativus L.), has not been fully studied yet. The distributional patterns of chromosome-level genome assembly in cucumber provide a fundamental basis for a genome-wide comparative analysis of CLE genes in such plants. RESULTS: A total of 26 individual CLE genes were identified in Chinese long '9930' cucumber, the majority of which belong to unstable short alkaline and hydrophilic peptides. A comparative analysis showed a close relationship in the development of CLE genes among Arabidopsis thaliana, melon, and cucumber. Half of the exon-intron structures of all CsCLEs genes are single-exon genes, and motif 1, a typical CLE domain near the C-terminal functioning in signal pathways, is found in all cucumber CLE proteins but CsCLE9. The analysis of CREs (Cis-Regulatory Elements) in the upstream region of the 26 cucumber CLE genes indicates a possible relationship between CsCLE genes and certain functions of hormone response elements. Cucumber resulted closely related to Arabidopsis and melon, having seven and 15 orthologous CLE genes in Arabidopsis and melon, respectively. Additionally, the calculative analysis of a pair of orthologous genes in cucumber showed that as a part of the evolutionary process, CLE genes are undergoing a positive selection process which leads to functional differentiation. The specific expression of these genes was vigorous at the growth and development period and tissues. Cucumber gene CLV3 was overexpressed in Arabidopsis, more than half of the transformed plants in T1 generation showed the phenomena of obvious weakness of the development of growing point, no bolting, and a decreased ability of plant growth. Only two bolted strains showed that either the pod did not develop or the pod was short, and its development was significantly inferior to that in the wild type. CONCLUSIONS: In this study, 26 CLE genes were identified in Chinese long '9930' cucumber genome. The CLE genes were mainly composed of alkaline hydrophilic unstable proteins. The genes of the CLE family were divided into seven classes, and shared close relationships with their homologs in Arabidopsis and melon. The specific expression of these genes was evaluated in different periods of growth and tissue development, and CLV3, which the representative gene of the family, was overexpressed in Arabidopsis, suggesting that it has a role in bolting and fruit bearing in cucumber.

Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signalling pathways.

Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high-glucose and high-fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high-glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin -induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91phox , Cyt-Cyto C), enhanced cell apoptosis (Bax/Bcl-2, Cleaved caspase-3, TUNEL-positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1-Foxo1 and PI3K-Akt pathways.

A panel of DNA methylated markers predicts metastasis of pN0M0 gastric carcinoma: a prospective cohort study.

BACKGROUND: The aim of this prospective study was to evaluate the feasibility of predicting GC metastasis using CDH1, GFRA1, P16 and ZNF382 DNA methylation as biomarkers. METHODS: 198 GC patients without metastasis at the time of surgery resection were recruited into the double-blind cohort (NCT02159339). Gene methylation was analysed using MethyLight assays. GC metastasis and survival data were obtained from 178 patients with 94.7% compliance during follow-up. RESULTS: Twenty six cases of metastasis and 5 cases of recurrence were observed in 178 cases (17.4%) during the follow-up (median, 62.7 months). The GC metastasis rate for GFRA1 methylation-positive patients was significantly reduced compared with GFRA1 methylation-negative patients (odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.08-0.66). Similar results were also observed using ZNF382 methylation as a predictor (OR: 0.17, 95% CI 0.06-0.47). A risk score including methylation of GFRA1 and ZNF382 was generated. The metastasis rate was significantly increased in high-risk GC patients (OR: 4.71, 95% CI: 1.85-12.00). GC patients with high risk had a shorter overall survival, especially for patients with stage I GC (P = 0.024). CONCLUSIONS: The combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis.

Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK.

Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.

Luteolin Ameliorates Cognitive Impairments by Suppressing the Expression of Inflammatory Cytokines and Enhancing Synapse-Associated Proteins GAP-43 and SYN Levels in Streptozotocin-Induced Diabetic Rats.

Luteolin, a flavonoid isolated from Cirsium japonicum, has antioxidant, anti-inflammatory and neuroprotective activities. Our previous studies brought a prospect that luteolin benefited diabetic rats with cognitive impairments. In this study, we examined whether luteolin could suppress the inflammatory cytokines, thus increasing synapse-associated proteins in streptozotocin (STZ)-induced diabetes in rat models. The model rats underwent luteolin treatment for 8 consecutive weeks, followed by assessment of cognitive performances with MWM test. Nissl staining was employed to assess the neuropathological changes in the hippocampus and the effects of luteolin on diabetic rats. With animals sacrificed, expressions of inflammatory cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and synapse-associated proteins including growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were determined. The results affirmed improvement of behavioral performances in the MWM test, downexpression of glycation end products (AGEs) in the plasma and the receptor for advanced glycation end products in the hippocampus, inhibition of IL-1ß and TNF-α in both the hippocampus and plasma in diabetic rats. Furthermore, luteolin treatment upregulated the expressions of GAP-43 and SYN in the hippocampus. Thus, luteolin could ameliorate the cognitive dysfunctions in STZ-induced diabetic rat model.

MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer.

BACKGROUND: We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. METHODS: We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. RESULTS: Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. CONCLUSIONS: MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy.

Exploration of significant influences of the operating conditions on the local O2 transport in proton exchange membrane fuel cells (PEMFCs).

A drastic reduction of the Pt loading in the cathode catalyst layers (CCLs) of proton exchange membrane fuel cells (PEMFCs) is much desired. However, a decrease in Pt loading inevitably leads to an unexpected increase of local O2 transport resistance (rLocal) and severely weakens the fuel cell performance, particularly at high current densities. Thus, it is both urgent and meaningful to explore the impacts of the operating conditions on rLocal in CCLs and therefore to clarify the intrinsic mechanism. Herein, we systematically explore the influences of the operating conditions, in terms of the dry O2 mole fraction, the relative humidity, the operating pressure and the temperature on rLocal using limiting current measurements combined with mathematical calculations. The results show that, in contrary to the established rules, rLocal in CCLs of PEMFCs is aggravated when the dry O2 mole fraction or the operating pressure are increased. It is also experimentally found that rLocal in CCLs is alleviated with the increase in the relative humidity or the operating temperature. Moreover, an adsorption controlled solution-diffusion model is proposed to illuminate the local O2 transport behavior in CCLs of PEMFCs, and it accounts for the influence of the dry O2 mole fraction on rLocal in CCLs.

Trichostatin A potentiates TRAIL-induced antitumor effects via inhibition of ERK/FOXM1 pathway in gastric cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal apoptosis inducer and believed to have promise in cancer therapy, yet part of cancer cells exhibit resistance to TRAIL-mediated apoptosis. This necessitates the exploration of agents that resensitizes cancer cells to TRAIL. In our study, we found that Trichostatin A (TSA), an histone deacetylase (HDAC) inhibitor, augmented TRAIL-induced apoptosis in gastric cancer cells in a caspase-dependent manner. Besides, upregulation of DR5 and downregulation of anti-apoptotic proteins including XIAP, Mcl-1, Bcl-2 and Survivin also contributed to this synergism. Noticeably, TSA treatment inhibited Forkhead boxM1 (FOXM1), which expression level showed negative correlation with TRAIL sensitivity. Similarly, silencing of FOXM1 by small interfering RNA (siRNA) resensitized cancer cells to TRAIL and strengthened the TRAIL-augmenting effect of TSA. In addition, we demonstrated the depletion of FOXM1 was a consequence of the inactivation of ERK mediated by TSA. Collectively, it was first shown that TSA potentiated TRAIL sensitivity via ERK/FOXM1 pathway in gastric cancer cells. FOXM1 might serve as a biomarker for predicting sensitivity to TRAIL.

Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor survival in patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. METHODS: Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays). RESULTS: In the 129 patients, a copy number gain of three chromosome regions-namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator. CONCLUSIONS: Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.

[Diagnostic value of FibroTest for liver fibrosis in patients with chronic hepatitis B].

OBJECTIVE: To determine the diagnostic value of FibroTest (FT) for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: One hundred and forty-two patients with CHB were tested for the following five indicators: alpha2-microglobulin (a2-MG), haptoglobin (Hp), gamma-glutarnyl peptidase (GGT), total bilirubin (TBIL), and apolipoprotein A1 (ApoA1). The resultant data, along with the age and sex of the patients, were put into an algorithm to compute the final results of the FT. During the same period of FT, all of the CHB patients underwent liver stiffness measurement by FibroScan (FS) as well as liver biopsy. Considering the liver biopsy as the gold standard, we determined receiver operating characteristic (ROC) curves at different endpoints. Calculation of the area under the ROC curves (AUROC) was performed to evaluate the diagnostic importance of FT, FS towards the treatment of liver fibrosis in patients with CHB. RESULTS: Significant fibrosis (Scheuer score (S) more than or equal to 2) was predicted with an AUROC for FS, FT of 0.827 (0.753-0.900), 0.897 (0.844-0.949). Significant fibrosis (S more than or equal to 3) was predicted with an AUROC for FS, FT of 0.883 (0.818-0.949), 0.968 (0.932-1.00). Significant fibrosis (S=4) was predicted with an AUROC for FS, FT of 0.943 (0.893-0.993), 0.991 (0.973-1.00). CONCLUSION: s FT is a novel tool that can be used to assess the degree of fibrosis in patients with CHB.

Giant piezoelectricity in potassium-sodium niobate lead-free ceramics.

Environment protection and human health concern is the driving force to eliminate the lead from commercial piezoelectric materials. In 2004, Saito et al. [ Saito et al., Nature , 2004 , 432 , 84 . ] developed an alkali niobate-based perovskite solid solution with a peak piezoelectric constant d33 of 416 pC/N when prepared in the textured polycrystalline form, intriguing the enthusiasm of developing high-performance lead-free piezoceramics. Although much attention has been paid on the alkali niobate-based system in the past ten years, no significant breakthrough in its d33 has yet been attained. Here, we report an alkali niobate-based lead-free piezoceramic with the largest d33 of ∼490 pC/N ever reported so far using conventional solid-state method. In addition, this material system also exhibits excellent integrated performance with d33∼390-490 pC/N and TC∼217-304 °C by optimizing the compositions. This giant d33 of the alkali niobate-based lead-free piezoceramics is ascribed to not only the construction of a new rhombohedral-tetragonal phase boundary but also enhanced dielectric and ferroelectric properties. Our finding may pave the way for "lead-free at last".