FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. Here, we identified FBXO32 as an oncogenic driver in PDAC. FBXO32 was aberrantly upregulated in PDAC, and high FBXO32 expression was significantly associated with an unfavorable prognosis in PDAC patients. FRG1 deficiency promoted FBXO32 upregulation in PDAC. FBXO32 promoted cell migration and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, FBXO32 directly interacted with eEF1A1 and promoted its polyubiquitination at the K273 site, leading to enhanced activity of eEF1A1 and increased protein synthesis in PDAC cells. Moreover, FBXO32-catalyzed eEF1A1 ubiquitination boosted the translation of ITGB5 mRNA and activated FAK signaling, thereby facilitating focal adhesion assembly and driving PDAC progression. Importantly, interfering with the FBXO32-eEF1A1 axis or pharmaceutical inhibition of FAK by defactinib, an FDA-approved FAK inhibitor, substantially inhibited PDAC growth and metastasis driven by aberrantly activated FBXO32-eEF1A1 signaling. Overall, this study uncovers a mechanism by which PDAC cells rely on FBXO32-mediated eEF1A1 activation to drive progression and metastasis. FBXO32 may serve as a promising biomarker for selecting eligible PDAC patients for treatment with defactinib.

Thromboxane A2 Modulates de novo Synthesis of Adrenal Corticosterone in Mice via p38/14-3-3γ/StAR Signaling.

Prostanoids are endogenous lipid bioactive mediators that play essential roles in physiological processes such as glucocorticoid secretion. Here, it is found that the thromboxane (Tx)A2 receptor (TP) is highly expressed in the adrenal cortex of mice. Both global and adrenocortical-specific deletion of the TP receptor lead to increased adiposity in mice by elevating corticosterone synthesis. Mechanistically, the TP receptor deletion increases the phosphorylation of steroidogenic acute regulatory protein (StAR) and corticosterone synthesis in adrenal cortical cells by suppressing p-p38-mediated phosphorylation of 14-3-3γ adapter protein at S71. The activation of the p38 in the adrenal cortical cells by forced expression of the MKK6EE gene attenuates hypercortisolism in TP-deficient mice. These observations suggest that the TxA2/TP signaling regulates adrenal corticosterone homeostasis independent of the hypothalamic-pituitary-adrenal axis and the TP receptor may serve as a promising therapeutic target for hypercortisolism.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Thyroglobulin as a Sensitive Biomarker of Iodine Status in Mildly and Moderately Iodine-Deficient Pregnant Women.

Pregnant women are more susceptible to iodine deficiency. However, there are limitations in existing indicators for the evaluation of iodine nutrition in pregnant women. The study aimed to explore whether thyroglobulin (Tg) can be used as a more sensitive biomarker for pregnant women with mild and moderate iodine deficiency. A repeated-measure study was conducted among 1332 pregnant women in Zhejiang Province, China. Serum and urine specimens were collected at a mean of 10, 17, and 32 weeks of pregnancy, respectively; thyroid-stimulating hormone (TSH), Tg, and urinary iodine concentrations were measured. Linear mixed effects models were used to determine the associations between interaction of iodine concentrations and increasing gestation week and TSH and Tg, where participants were divided by urinary iodine concentration (UIC). The median Tg concentration was 11.56, 11.45, and 12.43 µg/L in the first, second, and third trimesters, respectively. After controlling the covariates, the interaction effects between the iodine status and gestation week were significant for both TSH and Tg (p = 0.038 and p = 0.007, respectively). TSH increased with the week of gestation in both iodine concentration groups. Tg increased with advancing pregnancy in the iodine-deficient group whereas it did not in the iodine-sufficient group. There was no significant variation in TSH at each trimester, and Tg was higher in the iodine-deficient group than in the iodine-sufficient group. Tg may be a more sensitive iodine status biomarker than TSH for pregnant women with mild-to-moderate iodine insufficiency.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

DHX38 restricts chemoresistance by regulating the alternative pre-mRNA splicing of RELL2 in pancreatic ductal adenocarcinoma.

Intron retention plays an important role in cancer progression and chemotherapy resistance and seems to be essential for the maintenance of genome stability in cancer. Here, our goal was to analyze the role of receptor expressed in lymphoid tissue (Relt)-like 2 (RELL2) intron 4 retention in promoting pancreatic ductal adenocarcinoma (PDAC) progression. Our results showed that intron retention (IR) occurs at the fourth intron of RELL2 transcript in gemcitabine resistant PDAC cells, however, the regulatory mechanism and the clinical implications of IR of RELL2 are unclear. Firstly, we found that RELL2 plays an anti-oncogenic role in PDAC by performing in vitro functional assays including cell proliferation, GEM cytotoxicity assay and apoptosis. Subsequently, we identified the upstream gene of RELL2, DEAH-Box Helicase 38 (DHX38), and demonstrated the direct interaction between DHX38 and RELL2 by RIP-qPCR. We also found that altered expression of DHX38 resulted in corresponding changes in intron 4 retention of RELL2. Importantly, we unveiled that overexpression of DHX38 on the basis of knocking down of the fourth intron of RELL2 resulted in an impaired intron 4 intention. Overall, our study identified a new IR site in PDAC, which could be a possible target for PDAC therapy.

Pancreatic cancer stemness: dynamic status in malignant progression.

Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide. Increasing evidence suggests that the capacity for self-renewal, proliferation, and differentiation of pancreatic cancer stem cells (PCSCs) contribute to major challenges with current PC therapies, causing metastasis and therapeutic resistance, leading to recurrence and death in patients. The concept that PCSCs are characterized by their high plasticity and self-renewal capacities is central to this review. We focused specifically on the regulation of PCSCs, such as stemness-related signaling pathways, stimuli in tumor cells and the tumor microenvironment (TME), as well as the development of innovative stemness-targeted therapies. Understanding the biological behavior of PCSCs with plasticity and the molecular mechanisms regulating PC stemness will help to identify new treatment strategies to treat this horrible disease.

EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway.

BACKGROUND: The prognosis of pancreatic cancer patients remains relatively poor. Although some patients would receive surgical resection, distant metastasis frequently occurs within one year. Epithelial-mesenchymal transition (EMT), as a pathological mechanism in cancer progression, contributed to the local and distant metastasis of pancreatic cancer. METHODS: Tissue microarray analysis and immunohistochemistry assays were used to compare the expression of EGR1 in pancreatic cancer and normal pancreatic tissues. Transwell chambers were used to evaluated the migration and invasion ability of cancer cells. Immunofluorescence was utilized to assess the expression of E-cadherin. ChIP-qPCR assay was applied to verify the combination of EGR1 and SNAI2 promoter sequences. Dual-luciferase reporter assay was used to detect the gene promoter activation. Co-IP assay was conducted to verify the interaction of EGR1 and p300/CBP. RESULTS: EGR1 was highly expressed in pancreatic cancer rather than normal pancreatic tissues and correlated with poor prognosis and cancer metastasis. EGR1 was proved to enhance the migration and invasion ability of pancreatic cells. Besides, EGR1 was positively correlated with EMT process in pancreatic cancer, via a SNAI2-dependent pathway. P300/CBP was found to play an auxiliary role in the transcriptional activation of the SNAI2 gene by EGR1. Finally, in vivo experiments also proved that EGR1 promoted liver metastasis of pancreatic cancer. CONCLUSION: Our findings implied the EMT-promoting effect of EGR1 in pancreatic cancer and revealed the intrinsic mechanism. Blocking the expression of EGR1 may be a new anticancer strategy for pancreatic cancer.

STOML2 restricts mitophagy and increases chemosensitivity in pancreatic cancer through stabilizing PARL-induced PINK1 degradation.

Pancreatic cancer remains one of the most lethal diseases with a relatively low 5-year survival rate, and gemcitabine-based chemoresistance occurs constantly. Mitochondria, as the power factory in cancer cells, are involved in the process of chemoresistance. The dynamic balance of mitochondria is under the control of mitophagy. Stomatin-like protein 2 (STOML2) is located in the mitochondrial inner membrane and is highly expressed in cancer cells. In this study, using a tissue microarray (TMA), we found that high STOML2 expression was correlated with higher survival of patients with pancreatic cancer. Meanwhile, the proliferation and chemoresistance of pancreatic cancer cells could be retarded by STOML2. In addition, we found that STOML2 was positively related to mitochondrial mass and negatively related to mitophagy in pancreatic cancer cells. STOML2 stabilized PARL and further prevented gemcitabine-induced PINK1-dependent mitophagy. We also generated subcutaneous xenografts to verify the enhancement of gemcitabine therapy induced by STOML2. These findings suggested that STOML2 regulated the mitophagy process through the PARL/PINK1 pathway, thereby reducing the chemoresistance of pancreatic cancer. STOML2-overexpression targeted therapy might be helpful for gemcitabine sensitization in the future.

Multidrug resistance genes screening of pancreatic ductal adenocarcinoma based on sensitivity profile to chemotherapeutic drugs.

BACKGROUNDS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types and chemotherapeutic drug resistance is a stumbling block in improving the overall survival of PDAC patients. The nature of specific drug resistant subpopulation within pancreatic ductal adenocarcinoma is believed to be partly attributed to epithelial-mesenchymal transition (EMT) and cell stemness. Various PDAC cell lines show various degrees of resistance to chemotherapeutic agents including gemcitabine (GEM) and 5-fluorouracil (5-FU). In-depth understanding of drug resistance mechanisms and profile heterogeneities could lead to the development of novel and precise therapeutic strategies for addressing the chemo-resistant dilemma in PDAC patients. METHODS: Cytotoxicity assays were performed by CCK8 in ten common PDAC cell lines including AsPC-1, BxPC-3, CAPAN-1, CFPAC, HPAFII, MIA PaCa-2, PANC-1, Patu-8988, SW1990 and T3M4. RNA-seq data of the ten cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE) database and subsequently analyzed for differentially expressed genes (DEGs). Based on first-line chemotherapy regimens of PDAC, DEGs between resistant and sensitive cell lines were validated by qRT-PCR. Enriched pathways of differentially expressed genes between the resistant and sensitive cell lines were acquired by Metascape database. RESULTS: We found that the top two toxic drugs for PDAC cell lines were paclitaxel (PTX) and GEM. Among the ten PDAC cell lines, SW1990 was the most resistant PDAC cell line with the highest IC50 levels for three drugs, while MIA PaCa-2 and BxPC-3 were the most sensitive PDAC cell lines. Differential expression analysis revealed the highest number of DEGs associated with cisplatin (CIS) sensitivity up to 642 genes, of which 181 genes were upregulated and 461 genes were downregulated in CIS-resistant cell lines. The least number of DEGs are associated with GEM sensitivity, of which 37 genes were highly expressed in GEM-resistant PDAC cell lines and 25 genes were lowly expressed. Enrichment analysis of the DEGs revealed that pathways associated with drug resistance were mainly extracellular matrix and cell-cell junction related pathways. CONCLUSIONS: PDAC cell lines showed diverse sensitivities to commonly used chemotherapeutic agents, which was caused by differential gene expression between the resistant and sensitive cell lines. The heterogeneity and its associated genes were enriched in extracellular matrix and cell-cell junction related pathways. Our study first portrayed the sensitivity profile to chemotherapeutic drugs of PDAC, which would benefit the chemoresistance mechanism study by reemphasizing the vital role of extracellular matrix and cell-cell junction related pathways and helping the selection of suitable PDAC cell lines.

CHRNB2 represses pancreatic cancer migration and invasion via inhibiting ß-catenin pathway.

BACKGROUND: Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear. METHODS: Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and ß-catenin pathway via Western Blot. RESULTS: High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated ß-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2. CONCLUSIONS: CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit ß-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.

Phospholipase A/acyltransferase 4 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer.

Background: Phospholipase A/acyltransferase (PLAAT) family exhibits O- and N-acyltransferase activity and biosynthesize N-acylated ethanolamine phospholipids. Previously, PLAAT4 was seen as a tumor suppressor, but the exact function of PLAAT4 in pancreatic cancer was still unknown. In this study, we investigated the relationship of PLAAT4 and pancreatic cancer. Methods: Using the data from the cancer genome atlas (TCGA), Genotype-Tissue Expression (GTEx) database and Gene Expression Omnibus (GEO) datasets we compared the expression of PLAAT4 in normal and tumor tissues and analyzed the connections between PLAAT4 and several clinicopathological factors. Further, we conducted Gene ontology (GO) analysis, Gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA) and estimate analysis to explore the association between PLAAT4 and biological function and immune infiltration. In addition, Kaplan-Meier (KM) analysis, univariate and multivariate Cox analysis were used to explore the association between PLAAT4 and prognosis. In addition, we plotted a nomogram according to the multivariate cox analysis visualizing the predictive ability of PLAAT4 on prognosis. In addition, we explore the influence of PLAAT4 on malignant behaviors of the pancreatic cancer cells in vitro. Results: After comparing the expression of PLAAT4 in normal and tumor tissues, we found that the expression of PLAAT4 was significantly high in pancreatic ductal adenocarcinoma (PDAC) samples. In addition, the results of GO and GSEA found that the expression of PLAAT4 was related to cell cycle checkpoints, M phase, regulation by p53, cell cycle mitotic and etc. Further, ssGSEA has shown that PLAAT4 was positively related to the abundance of aDC, Th1 cells, Th2 cells and negatively related to the Th17 cells. Subsequently, KM analysis, univariate and multivariate Cox analysis were used to analyze the correlation between PLAAT4 and prognosis. Additionally, we found that higher expression of PLAAT4 was related to T stage, N stage, histologic grade, etc (P < 0.05) and has a significant correlation with poor Overall Survival (OS), Disease-Specific Survival (DSS) and Progression-Free Interval (PFI). At last, we proved that PLAAT4 contributed to the malignant behaviors of the pancreatic cancer cells. Conclusion: This study indicated PLAAT4 as a novel prognostic biomarker and an important molecular that mediated immune response in pancreatic cancer.

Chromatin Dynamics in Digestive System Cancer: Commander and Regulator.

Digestive system tumors have a poor prognosis due to complex anatomy, insidious onset, challenges in early diagnosis, and chemoresistance. Epidemiological statistics has verified that digestive system tumors rank first in tumor-related death. Although a great number of studies are devoted to the molecular biological mechanism, early diagnostic markers, and application of new targeted drugs in digestive system tumors, the therapeutic effect is still not satisfactory. Epigenomic alterations including histone modification and chromatin remodeling are present in human cancers and are now known to cooperate with genetic changes to drive the cancer phenotype. Chromatin is the carrier of genetic information and consists of DNA, histones, non-histone proteins, and a small amount of RNA. Chromatin and nucleosomes control the stability of the eukaryotic genome and regulate DNA processes such as transcription, replication, and repair. The dynamic structure of chromatin plays a key role in this regulatory function. Structural fluctuations expose internal DNA and thus provide access to the nuclear machinery. The dynamic changes are affected by various complexes and epigenetic modifications. Variation of chromatin dynamics produces early and superior regulation of the expression of related genes and downstream pathways, thereby controlling tumor development. Intervention at the chromatin level can change the process of cancer earlier and is a feasible option for future tumor diagnosis and treatment. In this review, we introduced chromatin dynamics including chromatin remodeling, histone modifications, and chromatin accessibility, and current research on chromatin regulation in digestive system tumors was also summarized.

Analysis of Movements and Behavior of Bighead Carps (Hypophthalmichthys nobilis) Considering Fish Passage Energetics in an Experimental Vertical Slot Fishway.

An understanding of fish movement behavior in response to flow field variables is important for exploring the hydrodynamic strategies of fish in fish passages. In this paper, bighead carps were taken as an example. The fish movement behavior response to water flow field information by means of estimating the energetic expenditure using an IBM approach in an experimental fishway was investigated. Fish swimming velocity, drag force, and energy expenditure were analyzed in varied flow conditions related to hydraulic variables, including velocity (V), turbulent kinetic energy (TKE), and strain rate (SR). The result indicated that the fish will require more energy in high TKE zones. This study provides a reference for optimizing the design of fish passages and fisheries management. This method can be applied to assess the efficiency of fish bypass structures and conduct fish survival studies.

Long Noncoding RNA and Circular RNA: Two Rising Stars in Regulating Epithelial-Mesenchymal Transition of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with especially poor prognosis. However, the molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Epithelial-mesenchymal transition (EMT) process is important to drive pancreatic carcinogenesis. Recently, long noncoding RNAs (lncRNAs) and circular RNAs(circRNAs) have been characterized to participate in EMT in PDAC, which can affect the migration and invasion of tumor cells by playing important roles in epigenetic processes, transcription, and post-transcriptional regulation. LncRNAs can act as competing endogenous RNAs (ceRNA) to sequester target microRNAs(miRNAs), bind to the genes which localize physically nearby, and directly interact with EMT-related proteins. Currently known circRNAs mostly regulate the EMT process in PDAC also by acting as a miRNA sponge, directly affecting the protein degradation process. Therefore, exploring the functions of lncRNAs and circRNAs in EMT during pancreatic cancer might help pancreatic cancer treatments.

The effects of temperature variability on mortality in patients with chronic obstructive pulmonary disease: a time-series analysis in Hangzhou, China.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in people aged over 60 years old. Research has been reported that ambient temperature and diurnal temperature range (DTR), as representative indices of temperature variability, are contributors to the development and exacerbation of COPD. However, few studies are available in Chinese population. In this study, we aimed to assess the associations of temperature variability on COPD mortality in a fast developing city in China. Using the mortality surveillance system, we obtained a total of 7,863 deaths attributed to COPD from 2014 to 2016. Quasi-Poisson generalized linear regression with distributed lag non-linear model was applied to explore the associations between temperature variability and COPD deaths, after controlling for the potential confounders, including relative humidity, day of week, public holiday, and long-term trend. A J-shaped association of DTR and a reversely J-shaped association of temperature for COPD mortality were observed. Risk estimates showed that the relative risks (RRs) of COPD mortality with extreme high DTR at lag 0 and 0-7 days were 1.045 (95% CI: 0.949-1.151) and 1.460 (95% CI: 1.118-1.908), and the extreme high temperature at lag 0 and 0-7 days were 1.090 (95% CI: 0.945-1.256) and 1.352 (95% CI: 1.163-1.572). Our findings suggest that short-term exposure to extreme temperature was associated with mortality for COPD in Hangzhou. The evidence has implications for policy decision-making and targeted interventions.

Stiffness in breast masses with posterior acoustic shadowing: significance of ultrasound real time shear wave elastography.

BACKGROUND: To assess the stiffness of benign breast masses in ultrasound images with posterior acoustic shadowing (PAS) and malignant lesions, and explore the significance of differential diagnosis using ultrasound real time shear wave elastography. MATERIAL AND METHODS: All 117 mammary masses (98 patients) with PAS were assessed by using routine ultrasound examination, and elastic modulus values were obtained with the real time shear wave elastography mode. All breast lesions were confirmed by surgery or biopsy. The significance of differences in ultrasound elastography values between breast benign and malignant masses with posterior acoustic shadowing was assessed, and the ROC curves of elasticity modulus values were analyzed. RESULTS: Among the 117 masses, 72 were benign and 45 were malignant. The two types of breast masses showed significant differences in size, margin, internal echo, calcification, and blood flow characteristics (P < 0.05), although the difference in orientation was not significant (P > 0.05). Emean, Emax and Esd obtained with real time shear wave elastography showed statistically significant differences between benign masses with posterior acoustic shadowing and breast cancer (P < 0.05), while Emin showed no significant difference between them (P = 0.633). Ultrasound real time shear wave elastography showed higher sensitivity and specificity than conventional ultrasound. CONCLUSIONS: Benign and malignant breast masses with PAS show different ultrasound manifestations. Real time shear wave elastography can facilitate the differential diagnosis and treatment planning for these breast masses.

Catalytic Performance of Li/Mg Composites for the Synthesis of Glycerol Carbonate from Glycerol and Dimethyl Carbonate.

A series of Li/Mg composites were synthesized by the coprecipitation method using magnesium and lithium nitrates, and then used for the synthesis of glycerol carbonate (GC) from glycerol and dimethyl carbonate (DMC). The experimental results indicated that Li/Mg composites were prospective catalysts for GC synthesis. 92.05% glycerol conversion and 90.61% GC yield were obtained after reacting at 80 °C for 2 h in the presence of Li/Mg composites. The structure and properties of Li/Mg composites were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Brunauer-Emmett-Teller (BET), and CO2-temperature-programmed desorption (TPD) techniques. It was inferred that the basic strength and basicity of Li/Mg composites were improved with increase in Li content. It was concluded that Li2CO3 was the main reactive species. A too-strong basic strength of Li/Mg composites could facilitate the glycerol conversion but impair GC selectivity.