Immortalization-upregulated protein promotes pancreatic cancer progression by regulating NPM1/FHL1-mediated cell-cycle-checkpoint protein activity.

Immortalization-upregulated protein (IMUP) plays a vital role in cell proliferation and tumor progression. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we select IMUP as an alternative gene based on GeneChip analysis of clinical PDAC tissues and transcriptome data from The Cancer Genome Atlas. IMUP expression is upregulated in PDAC tumor tissues. Moreover, high IMUP expression correlates with poor prognosis, while IMUP depletion inhibits PDAC cell proliferation and colony formation capacity in vitro, and decreases xenograft tumor growth in vivo. IMUP downregulation leads to cell-cycle arrest in the S phase. IMUP knockdown increases the expression of four-and-a-half LIM domain protein 1 (FHL1), which regulates the phosphorylation of cell division cycle 25A (CDC25A) by cycle checkpoint kinase 1 (CHK1) and promotes cytoplasmic distribution of CDC25A by interaction with 14-3-3ξ. Furthermore, FHL1 knockdown restores the effects induced by IMUP depletion. Liquid chromatography tandem mass spectrometry and immunoprecipitation analysis further show that IMUP interacts directly with nucleophosmin (NPM1) and enhances its stability. DNA methylation sequencing shows that FHL1 promoter methylation decreases when IMUP is downregulated. Overexpression of NPM1 can increase the methylation level of FHL1, thereby decreasing its expression. Our study provides a novel perspective on IMUP/NPM1/FHL1-mediated cell-cycle arrest by regulating CDC25A phosphorylation in PDAC. These findings may provide a new therapeutic target for PDAC.

The role of strigolactone analog (GR24) in endogenous hormone metabolism and hormone-related gene expression in tobacco axillary buds.

KEY MESSAGE: Strigolactone has the potential to influence hormone metabolism, in addition to having a role in inhibiting axillary bud elongation, which could be regulated by the expression of phytohormones-related genes. The elongation of axillary buds affects the economic benefits of tobacco. In this study, it was investigated the effect of strigolactone (SL) on the elongation of tobacco axillary buds and its endogenous hormone metabolism and related gene expression by applying the artificial analog of SL, GR24, and an inhibitor of SL synthesis, TIS-108, to the axillary buds. The results showed that the elongation of axillary buds was significantly inhibited by GR24 on day 2 and day 9. Ultra-high-performance liquid-chromatography-mass spectrometry results further showed that SL significantly affected the metabolism of endogenous plant hormones, altering both their levels and the ratios between each endogenous hormone. Particularly, the levels of auxin (IAA), trans-zeatin-riboside (tZR), N6-(∆2-isopentenyl) adenine (iP), gibberellin A4 (GA4), jasmonic acid (JA), and jasmonoyl isoleucine (JA-Ile) were decreased after GR24 treatment on day 9, but the levels of 1-aminocyclopropane-1-carboxylic acid (ACC) and gibberellin A1 (GA1) were significantly increased. Further analysis of endogenous hormonal balance revealed that after the treatment with GR24 on day 9, the ratio of IAA to cytokinin (CTK) was markedly increased, but the ratios of IAA to abscisic acid (ABA), salicylic acid (SA), ACC, JAs, and, GAs were notably decreased. In addition, according to RNA-seq analysis, multiple differentially expressed genes were found, such as GH3.1, AUX/IAA, SUAR20, IPT, CKX1, GA2ox1, ACO3, ERF1, PR1, and HCT, which may play critical roles in the biosynthesis, deactivation, signaling pathway of phytohormones, and the biosynthesis of flavonoids to regulate the elongation of axillary buds in tobacco. This work lays the certain theoretical foundation for the application of SL in regulating the elongation of axillary buds of tobacco.

Psychological Distress and Risk Factors in Frontline Nurses Confronting COVID-19 in Less Severely Affected Areas.

The current study investigated the prevalence and risk factors of somatization, depression, and anxiety among 374 frontline nurses in less severely affected areas during the initial period of the coronavirus disease 2019 (COVID-19) outbreak. The prevalence of somatization, depression, and anxiety among frontline nurses was 41.4%, 40.1%, and 37.4%, respectively. Nurses from provincial-level hospitals were less likely to report somatization (odds ratio [OR] = 0.50; p = 0.018), depression (OR = 0.52; p = 0.024), and anxiety (OR = 0.35; p < 0.001) than those from county-level hospitals. Longer service duration was significantly associated with a higher likelihood of reporting somatization (OR = 1.06; p = 0.008) and depression (OR = 1.06; p = 0.006). Psychological distress exists in frontline nurses in less severely affected areas, and hospital levels and service duration are independent risk factors for psychological stress in these nurses. Maintaining nurses' mental health is an important issue in addressing the COVID-19 pandemic in addition to sufficient distribution of medical resources between hospitals at different levels. [Journal of Psychosocial Nursing and Mental Health Services, 61(4), 37-44.].

Identifying cancer cell-secreted proteins that activate cancer-associated fibroblasts as prognostic factors for patients with pancreatic cancer.

The study aimed to investigate the mechanism by which cancer-associated fibroblasts (CAFs) are activated by cancer cells and construct a risk model to predict the prognosis of patients with pancreatic cancer (PC) after surgery. Pancreatic stellate cells were isolated from human pancreatic tissue and co-cultured with cancer cells to verify their crosstalk. Liquid chromatography-tandem mass spectrometry was used to detect proteins secreted by cancer cells. The online tools Gene Expression Profiling Interactive Analysis, UALCAN, and the Human Protein Atlas were used to analyse gene expression in PC. Expression data from the cancer genome atlas and the clinical samples were used to develop a training receiver operating characteristic (ROC) model and an external validation ROC model, respectively. We identified that cancer cells promote the activation of inflammatory CAFs (iCAF) through secretory proteins, which promote PC metastasis. Six candidate proteins secreted by cancer cells were identified which promote iCAF formation. These proteins were highly expressed in tumours and were associated with a poor prognosis in patients with PC. Moreover, a 6-gene model was constructed to predict death risk in patients at 1, 2 and 3 years after surgery. The training areas under the ROC curves (AUC) of 1-, 2- and 3-year death risks were 0.780, 0.792 and 0. 825, respectively. The externally validated AUC of death at 3 years post-surgery was 0.728. In conclusion, cancer cell-secreted proteins play a vital role in iCAF formation, and the 6-gene model may be a potential marker for predicting whether PC patients will benefit from surgery.

Alternate Mediterranean diet score is positively associated with skeletal muscle mass index in middle-aged adults.

Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008-2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011-2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all P trend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (P trend=0·03), 1·05, 0·52 and 1·20 %, (P trend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (P interaction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

Identification of predictive factors in hepatocellular carcinoma outcome: A longitudinal study.

Various surgical methods impact the prognosis of patients with hepatocellular carcinoma (HCC) differently. However, clinical guidelines remain inconsistent and the relative importance of predictors of survival outcomes requires further evaluation. The present study aimed to rank the importance of predictive factors that impact the survival outcomes of patients with HCC and to compare the prognosis associated with different surgical methods based on data obtained from the Surveillance, Epidemiology and End Results database. To achieve these aims, the present study used a random forest (RF) model to detect important predictive factors associated with survival outcomes in patients with HCC. Cox regression analysis was used to compare different surgery methods. The variables included in the Cox regression model were selected based on the Gini index calculated by the RF model. Using the RF model, the present study demonstrated that surgery method, tumor size and age were the first, second and third most important factors associated with HCC prognosis, respectively. Overall, patients who underwent local tumor destruction [(hazard ratio (HR)=0.48; 95% confidence interval (CI), 0.45-0.51; P<0.001)], wedge or segmental resection (HR, 0.31; 95% CI, 0.29-0.33; P<0.001), lobectomy (HR, 0.29, 95% CI, 0.27-0.31; P<0.001) or liver transplantation (HR, 0.16; 95% CI, 0.14-0.17; P<0.001) demonstrated improved overall survival time compared with those treated with surgery, with a gradual decreasing trend observed in HRs. The present study demonstrated that the surgical method used is the most important predictor of the survival outcomes of patients with HCC. Liver transplantation resulted in the best prognosis for patients with HCC, except for those with undifferentiated tumors or distant metastasis.

An Extreme Learning Machine Based on Artificial Immune System.

Extreme learning machine algorithm proposed in recent years has been widely used in many fields due to its fast training speed and good generalization performance. Unlike the traditional neural network, the ELM algorithm greatly improves the training speed by randomly generating the relevant parameters of the input layer and the hidden layer. However, due to the randomly generated parameters, some generated "bad" parameters may be introduced to bring negative effect on the final generalization ability. To overcome such drawback, this paper combines the artificial immune system (AIS) with ELM, namely, AIS-ELM. With the help of AIS's global search and good convergence, the randomly generated parameters of ELM are optimized effectively and efficiently to achieve a better generalization performance. To evaluate the performance of AIS-ELM, this paper compares it with relevant algorithms on several benchmark datasets. The experimental results reveal that our proposed algorithm can always achieve superior performance.

Modeling analysis of the relationship between atherosclerosis and related inflammatory factors.

Objective: To establish early diagnosis model of inflammatory factors for atherosclerosis (AS), providing theoretical evidence for early detection of AS and development of plaques. Methods: Serum samples were collected to detect the inflammatory factors including CysC, Hcy, hs-CRP, UA, FIB, D-D, LP (a), IL-6, SAA, sCD40L and MDA. Using Logistic regression analysis, the inflammatory factors used for modeling were screened out, and then the AS early diagnosis models were established based on receiver operating characteristic (ROC) curve, support vector machine and BP neural network respectively. Results: No significant difference exists between the general materials of two groups. All 11 inflammatory factors had higher level in AS group than in control group. As shown in ROC curve, all inflammatory factors were helpful in AS diagnosis. In terms of sensitivity, UA ranked first (98) and FIB ranked last (55.5); in terms of specificity, UA ranked first (99) and FIB ranked last (78); in terms of area under the curve, UA and SAA ranked first (both were 0.995) and FIB ranked last (0.721). Based on Logistic regression equation, six factors were screened out, including Hcy, Hs-CRP, IL-6, D-D, CysC and MDA. According to classification, the final sixth steps had a prediction accuracy of 99%. When six inflammatory factors included in Logistic regression equation were detected jointly, the sensitivity, specificity and area under the curve were 57%, 97% and 0.821 respectively, while those of the model excluding D-D were 64%, 90% and 0.828, generally superior to results of joint detection including six factors. The ROC curve based on Hcy, Hs-CRP and MDA had a sensitivity of 87%, a specificity of 94% and an area under the curve of 0.869, being inferior to those of the ROC curve based on IL-6, D-D and Cys C, which were 87%, 92% and 0.936 respectively. The accuracy of SVM-AS diagnosis model and BP neural network model were 82.5% and 77.5% respectively. Conclusion: All 11 inflammatory factors are valuable in AS diagnosis. AS early diagnosis models based on Logistic regression analysis, ROC curve, support vector machine and BP neural network possess diagnostic value and can provide reference for clinical diagnosis.

Greater Intake of Fruit and Vegetables Is Associated with Greater Bone Mineral Density and Lower Osteoporosis Risk in Middle-Aged and Elderly Adults.

OBJECTIVE: A few studies have suggested that the consumption of fruit and vegetables (FV) may benefit bone health, but limited data are available in Asian subjects. We examined the association between FV intake and bone mineral density (BMD) and osteoporosis in Chinese adults. METHODS: This population-based cross-sectional study involved 2083 women and 1006 men aged 40-75 years in Guangzhou, China. Habitual dietary data was collected from a 79-item food frequency questionnaire by face-to-face interviews. The BMD was measured for the whole body (WB), lumbar spine (LS), total hip (TH) and femur neck (FN) with dual-energy X-ray absorptiometry. RESULTS: After adjustment for potential covariates, we observed dose-dependent associations between total FV intake and BMD and osteoporosis risk. The mean BMD was higher in tertile 3 vs. tertile 1 by 1.33% (TH) and 1.31% (FN) for FV, and 1.10% (WB), 1.57% (TH), and 2.05% (FN) for fruit (all P-trends < 0.05). Significant beneficial associations with BMD at some sites were also found in most fruit categories but not in total vegetables or their subgroups. The odds ratios (95% confidence interval) of osteoporosis (T-score ≤ -2.5) in tertile 3 (vs. 1) were 0.73 (0.58-0.92), 0.37 (0.22-0.60), and 0.71 (0.52-0.97) for FV; 0.82 (0.66-1.03), 0.48 (0.30-0.77) and 0.89 (0.61-1.12) for fruit; and 0.80 (0.64-1.01), 0.57 (0.35-0.92) and 0.76 (0.55-1.05) for vegetables at the LS, TH, and FN, respectively. The favorable association between FV intake and the occurrence of osteoporosis was evident only in subjects with lower BMI (<24.0 kg/m2, P-trends < 0.05). CONCLUSIONS: Greater intake of FV was independently associated with a higher BMD and a lower presence of osteoporosis in middle-aged and elderly Chinese subjects with lower BMI. Fruit tended to have more contribution to the favorable association than vegetables.

Elevated Serum Uric Acid Is Associated with Greater Bone Mineral Density and Skeletal Muscle Mass in Middle-Aged and Older Adults.

BACKGROUND AND OBJECTIVE: Previous studies have suggested a positive link between serum uric acid (UA) and bone mineral density (BMD). In this study, we re-examined the association between UA and BMD and further explored whether this was mediated by skeletal muscle mass in a general Chinese population. METHOD: This community-based cross-sectional study was conducted among 3079 (963 men and 2116 women) Chinese adults aged 40-75 years. Face-to-face interviews and laboratory analyses were performed to determine serum UA and various covariates. Dual-energy X-ray absorptiometry was used to assess the BMD and appendicular skeletal muscle mass. The skeletal muscle mass index (SMI = ASM/Height(2), kg/m(2)) for the total limbs, arms, and legs was then calculated. RESULTS: The serum UA was graded and, in general, was significantly and positively associated with the BMD and muscle mass, after adjustment for multiple covariates in the total sample. Compared with participants in lowest quartile of UA, those participants in highest quartile showed a 2.3%(whole body), 4.1%(lumbar spine), 2.4%(total hip), and 2.0% (femoral neck) greater BMDs. The mean SMIs in the highest (vs. lowest) quartile increased by 2.7% (total), 2.5% (arm), 2.7% (leg) respectively. In addition, path analysis suggested that the favorable association between UA and BMD might be mediated by increasing SMI. CONCLUSION: The elevated serum UA was associated with a higher BMD and a greater muscle mass in a middle-aged and elderly Chinese population and the UA-BMD association was partly mediated by muscle mass.

Adherence to the Mediterranean diet is associated with a higher BMD in middle-aged and elderly Chinese.

Previous studies showed that better adherence to the Mediterranean diet (MD) is associated with lower risk of chronic diseases, but limited data are available on bone health. We investigated the association of the MD with bone mineral density (BMD) in Chinese adults. We included 2371 participants aged 40-75 years in this community-based cross-sectional study. Dietary information was assessed at baseline and a 3-year follow-up. Alternate Mediterranean diet (aMed) scores were calculated. BMD was determined at the second survey. After adjusting for potential covariates, higher aMed scores were positively and dose-dependently associated with BMD (all P-trends < 0.05). The BMD values were 1.94% (whole body), 3.01% (lumbar spine), 2.80% (total hip), 2.81% (femur neck), 2.62% (trochanter), and 2.85% (intertrochanter) higher in the quintile 5 (highest, vs. quintile 1) aMed scores for all of the subjects (all P-values < 0.05). Similar associations were found after stratifying by gender (P-interaction = 0.338-0.968). After excluding the five non-significant components of vegetables, legumes, fish, monounsaturated to saturated fat ratio, and alcohol intake from the aMed scores, the percentage mean differences were substantially increased by 69.1-150% between the extreme quintiles. In conclusion, increased adherence to the MD shows protective associations with BMD in Chinese adults.