Evaluation of sequence-based predictors for phase-separating protein.

Liquid-liquid phase separation (LLPS) of proteins and nucleic acids underlies the formation of biomolecular condensates in cell. Dysregulation of protein LLPS is closely implicated in a range of intractable diseases. A variety of tools for predicting phase-separating proteins (PSPs) have been developed with the increasing experimental data accumulated and several related databases released. Comparing their performance directly can be challenging due to they were built on different algorithms and datasets. In this study, we evaluate eleven available PSPs predictors using negative testing datasets, including folded proteins, the human proteome, and non-PSPs under near physiological conditions, based on our recently updated LLPSDB v2.0 database. Our results show that the new generation predictors FuzDrop, DeePhase and PSPredictor perform better on folded proteins as a negative test set, while LLPhyScore outperforms other tools on the human proteome. However, none of the predictors could accurately identify experimentally verified non-PSPs. Furthermore, the correlation between predicted scores and experimentally measured saturation concentrations of protein A1-LCD and its mutants suggests that, these predictors could not consistently predict the protein LLPS propensity rationally. Further investigation with more diverse sequences for training, as well as considering features such as refined sequence pattern characterization that comprehensively reflects molecular physiochemical interactions, may improve the performance of PSPs prediction.

Physicochemical Characterization of Asphaltenes Using Microfluidic Analysis.

Crude oils are complex mixtures of organic molecules, of which asphaltenes are the heaviest component. Asphaltene precipitation and deposition have been recognized to be a significant problem in oil production, transmission, and processing facilities. These macromolecular aromatics are challenging to characterize due to their heterogeneity and complex molecular structure. Microfluidic devices are able to capture key characteristics of reservoir rocks and provide new insights into the transport, reactions, and chemical interactions governing fluids used in the oil and gas industry. Understanding the microscale phenomena has led to better design of macroscale processes used by the industry. One area that has seen significant growth is in the area of chemical analysis under flowing conditions. Microfluidics and microscale analysis have advanced the understanding of complex mixtures by providing in situ imaging that can be combined with other chemical characterization methods to give details of how oil, water, and added chemicals interface with pore-scale detail. This review article aims to showcase how microfluidic devices offer new physical, chemical, and dynamic information on the behavior of asphaltenes. Specifically, asphaltene deposition and related flow assurance problems, interfacial properties and rheology, and evaluation of remediation strategies studied in microchannels and microfluidic porous media are presented. Examples of successful applications that address key asphaltene-related problems highlight the advances of microscale systems as a tool for advancing the physicochemical characterization of complex fluids for the oil and gas industry.

APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants. METHODS: Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes. RESULTS: An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade. CONCLUSIONS: Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.

LLPSDB v2.0: an updated database of proteins undergoing liquid-liquid phase separation in vitro.

SUMMARY: Emerging evidences have suggested that liquid-liquid phase separation (LLPS) of proteins plays a vital role both in a wide range of biological processes and in related diseases. Whether a protein undergoes phase separation not only is determined by the chemical and physical properties of biomolecule themselves, but also is regulated by environmental conditions such as temperature, ionic strength, pH, as well as volume excluded by other macromolecules. A web accessible database LLPSDB was developed recently by our group, in which all the proteins involved in LLPS in vitro as well as corresponding experimental conditions were curated comprehensively from published literatures. With the rapid increase of investigations in biomolecular LLPS and growing popularity of LLPSDB, we updated the database, and developed a new version LLPSDB v2.0. In comparison of the previously released version, more than double contents of data are curated, and a new class 'Ambiguous system' is added. In addition, the web interface is improved, such as that users can search the database by selecting option 'phase separation status' alone or combined with other options. We anticipate that this updated database will serve as a more comprehensive and helpful resource for users. AVAILABILITY AND IMPLEMENTATION: LLPSDB v2.0 is freely available at: http://bio-comp.org.cn/llpsdbv2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Disrupted topological organization of functional brain networks is associated with cognitive impairment in hypertension patients: a resting-state fMRI study.

PURPOSE: To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores. METHODS: Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized. RESULTS: HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network. CONCLUSION: This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.

Prediction of liquid-liquid phase separating proteins using machine learning.

BACKGROUND: The liquid-liquid phase separation (LLPS) of biomolecules in cell underpins the formation of membraneless organelles, which are the condensates of protein, nucleic acid, or both, and play critical roles in cellular function. Dysregulation of LLPS is implicated in a number of diseases. Although the LLPS of biomolecules has been investigated intensively in recent years, the knowledge of the prevalence and distribution of phase separation proteins (PSPs) is still lag behind. Development of computational methods to predict PSPs is therefore of great importance for comprehensive understanding of the biological function of LLPS. RESULTS: Based on the PSPs collected in LLPSDB, we developed a sequence-based prediction tool for LLPS proteins (PSPredictor), which is an attempt at general purpose of PSP prediction that does not depend on specific protein types. Our method combines the componential and sequential information during the protein embedding stage, and, adopts the machine learning algorithm for final predicting. The proposed method achieves a tenfold cross-validation accuracy of 94.71%, and outperforms previously reported PSPs prediction tools. For further applications, we built a user-friendly PSPredictor web server ( http://www.pkumdl.cn/PSPredictor ), which is accessible for prediction of potential PSPs. CONCLUSIONS: PSPredictor could identifie novel scaffold proteins for stress granules and predict PSPs candidates in the human genome for further study. For further applications, we built a user-friendly PSPredictor web server ( http://www.pkumdl.cn/PSPredictor ), which provides valuable information for potential PSPs recognition.

A (3,8)-Connected Metal-Organic Framework with Bending Dicarboxylate Linkers for C2H2/CO2 Separation.

Herein, by replacement of the linear terephthalate linker with the bending 2,5-thiophenedicarboxylate (tdc2-) linker in the typical (3,9)-connected metal-organic framework, with a reduced 8-connected hydroxyl-centered trinuclear cluster, a new (3,8)-connected network, [Ni3(µ3-OH)(tdc)3(tpp)] [DZU-1; tpp = 2,4,6-tris(4-pyridyl)pyridine], was synthesized. The modified pore environment enables DZU-1 to selectively adsorb C2H2 over CO2 in an efficient manner.

LLPSDB: a database of proteins undergoing liquid-liquid phase separation in vitro.

Liquid-liquid phase separation (LLPS) leads to a conversion of homogeneous solution into a dense phase that often resembles liquid droplets, and a dilute phase. An increasing number of investigations have shown that biomolecular condensates formed by LLPS play important roles in both physiology and pathology. It has been suggested the phase behavior of proteins would be not only determined by sequences, but controlled by micro-environmental conditions. Here, we introduce LLPSDB (http://bio-comp.ucas.ac.cn/llpsdb or http://bio-comp.org.cn/llpsdb), a web-accessible database providing comprehensive, carefully curated collection of proteins involved in LLPS as well as corresponding experimental conditions in vitro from published literatures. The current release of LLPSDB incorporates 1182 entries with 273 independent proteins and 2394 specific conditions. The database provides a variety of data including biomolecular information (protein sequence, protein modification, nucleic acid, etc.), specific phase separation information (experimental conditions, phase behavior description, etc.) and comprehensive annotations. To our knowledge, LLPSDB is the first available database designed for LLPS related proteins specifically. It offers plenty of valuable resources for exploring the relationship between protein sequence and phase behavior, and will enhance the development of phase separation prediction methods, which may further provide more insights into a comprehensive understanding of LLPS in cellular function and related diseases.

BMRMI Reduces Depressive Rumination Possibly through Improving Abnormal FC of Dorsal ACC.

Rumination is a common symptom of major depressive disorder (MDD) and has been characterized as a vulnerability factor for the onset or recurrence of MDD. However, the neurobiological mechanisms underlying rumination and appropriate treatment strategies remain unclear. In the current study, we used resting-state functional magnetic resonance imaging to investigate the effects of body-mind relaxation meditation induction (BMRMI) intervention in MDD with rumination. To this aim, we have recruited 25 MDD and 24 healthy controls (HCs). Changes in functional connectivity (FC) of the anterior cingulate cortex (ACC) subregion and the scores of clinical measurements were examined using correlation analysis. At baseline, MDD showed stronger FC between the right dorsal ACC (dACC) and right superior frontal gyrus than did the HC group. Compared to baseline, the HC group showed a significantly enhanced FC between the right dACC and right superior frontal gyrus, and the MDD group demonstrated a significantly weaker FC between the left dACC and right middle frontal gyrus (MFG) after the intervention. Furthermore, the FC between the right dACC and right superior frontal gyrus was positively associated with rumination scores across all participants at baseline. The above results indicate that BMRMI may regulate self-referential processing and cognitive function through modulating FC of the dACC in MDD with rumination.

Orf165 is associated with cytoplasmic male sterility in pepper.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that derives from the inability to produce functional pollen in higher plants. CMS results from recombination of the mitochondrial genome. However, understanding of the molecular mechanism of CMS in pepper is limited. In this study, comparative transcriptomic analyses were performed using a near-isogenic CMS line 14A (CMS-14A) and a maintainer line 14B (ML-14B) as experimental materials. A total of 17,349 differentially expressed genes were detected between CMS-14A and ML-14B at the PMC meiosis stage. Among them, six unigenes associated with CMS and 108 unigenes involved in energy metabolism were identified. The gene orf165 was found in CMS-14A. When orf165 was introduced into ML-14B, almost 30% of transgenic plants were CMS. In addition, orf165 expression in transgenic CMS plants resulted in abnormal function of some genes involved in energy metabolism. When orf165 in transgenic CMS plant was silenced, the resulted orf165-silenced plant was male fertile and the expression patterns of some genes associated with energy metabolism were similar to ML-14B. Thus, we confirmed that orf165 influenced CMS in pepper.

A novel single-base mutation in CaBRI1 confers dwarf phenotype and brassinosteroid accumulation in pepper.

Dwarfing is the development trend of pepper breeding. It is of great practical and scientific value to generate new dwarf germplasms, and identify new genes or alleles conferring dwarf traits in pepper. In our previous study, a weakly BR-insensitive dwarf mutant, E29, was obtained by EMS mutagenesis of the pepper inbred line 6421. It can be used as a good parent material for breeding new dwarf varieties. Here, we found that this dwarf phenotype was controlled by a single recessive gene. Whole-genome resequencing, dCAPs analysis, and VIGs validation revealed that this mutation was caused by a nonsynonymous single-nucleotide mutation (C to T) in CaBRI1. An enzyme activity assay, transcriptome sequencing, and BL content determination further revealed that an amino-acid change (Pro1157Ser) in the serine/threonine protein kinase and catalytic (S_TKc) domain of CaBRI1 impaired its kinase activity and caused the transcript levels of two important genes (CaDWF4 and CaROT3) participating in BR biosynthesis to increase dramatically in the E29 mutant, accompanied by significantly increased accumulation of brassinolide (BL). Therefore, we concluded that the novel single-base mutation in CaBRI1 conferred the dwarf phenotype and resulted in brassinosteroid (BR) accumulation in pepper. This study provides a new allelic variant of the height-regulating gene CaBRI1 that has theoretical and practical values for the breeding of the plants suitable for the facility cultivation and mechanized harvesting of pepper varieties.

Comparing the Coalescence Rate of Water-in-Oil Emulsions Stabilized with Asphaltenes and Asphaltene-like Molecules.

Asphaltenes are a significant contributor to flow assurance problems related to crude oil production. Because of their polydispersity, model molecules such as coronene and violanthrone-79 (VO-79) have been used as mimics to represent the physiochemical properties of asphaltenes. This work aims to evaluate the emulsion-stabilization characteristics of fractionated asphaltenes and these two model molecules. Such evaluation is expected to better characterize the stabilizing mechanisms of asphaltenes on water-in-oil emulsions. The coalescence process of water-in-oil emulsion droplets is visualized using a microfluidic flow-focusing geometry. The rate of coalescence events is used as the parameter to assess emulsion stability. Interfacial tension (IFT) and oil/brine zeta potential are measured to help explain the differences in the rates of coalescence. VO-79 is found to be better at stabilizing emulsions as compared to coronene. Although VO-79 and asphaltenes have similar interfacial tension and oil/brine zeta potential values, the rate of coalescence differs significantly. This highlights the difficulty in using model molecules to mimic the transport dynamics of asphaltenes.

Risk Factor Analysis and Risk Prediction Model Construction of Pressure Injury in Critically Ill Patients with Cancer: A Retrospective Cohort Study in China.

BACKGROUND The aim of this study was to analyze the risk factors of pressure injury (PI) in critically ill patients with cancer to build a risk prediction model for PI. MATERIAL AND METHODS Between January 2018 and December 2019, a total of 486 critically ill patients with cancer were enrolled in the study. Univariate analysis and binary logistic regression analysis were used to explore risk factors. Then, a risk prediction equation was constructed and a receiver operator characteristic (ROC) curve analysis model was used for prediction. RESULTS Of the 486 critically ill patients with cancer, 15 patients developed PI. Risk factors found to have a significant impact on PI in critically ill patients with cancer included the APACHE II score (P<0.001), semi-reclining position (P=0.006), humid environment/moist skin (P<0.001), and edema (P<0.001). These 4 independent risk factors were used in the regression equation, and the risk prediction equation was constructed as Z=0.112×APACHE II score +2.549×semi-reclining position +2.757×moist skin +1.795×edema-9.086. From the ROC curve analysis, the area under the curve (AUC) was 0.938, sensitivity was 100.00%, specificity was 83.40%, and Youden index was 0.834. CONCLUSIONS The PI risk prediction model developed in this study has a high predictive value and provides a basis for PI prevention and treatment measures for critically ill patients with cancer.

Protein Databases Related to Liquid-Liquid Phase Separation.

Liquid-liquid phase separation (LLPS) of biomolecules, which underlies the formation of membraneless organelles (MLOs) or biomolecular condensates, has been investigated intensively in recent years. It contributes to the regulation of various physiological processes and related disease development. A rapidly increasing number of studies have recently focused on the biological functions, driving, and regulating mechanisms of LLPS in cells. Based on the mounting data generated in the investigations, six databases (LLPSDB, PhaSePro, PhaSepDB, DrLLPS, RNAgranuleDB, HUMAN CELL MAP) have been developed, which are designed directly based on LLPS studies or the component identification of MLOs. These resources are invaluable for a deeper understanding of the cellular function of biomolecular phase separation, as well as the development of phase-separating protein prediction and design. In this review, we compare the data contents, annotations, and organization of these databases, highlight their unique features, overlaps, and fundamental differences, and discuss their suitable applications.

Comprehensive Phosphoproteomic Analysis of Pepper Fruit Development Provides Insight into Plant Signaling Transduction.

Limited knowledge is available for phosphorylation modifications in pepper (Capsicum annuum L.), especially in pepper fruit development. In this study, we conducted the first comprehensive phosphoproteomic analysis of pepper fruit at four development stage by Tandem Mass Tag proteomic approaches. A total of 2639 unique phosphopeptides spanning 1566 proteins with 4150 nonredundant sites of phosphorylation were identified, among which 2327 peptides in 1413 proteins were accurately quantified at four different stages. Mature Green (MG) to breaker stage showed the largest number of differentially expressed phosphoproteins and the number of downregulated phosphoproteins was significantly higher than that of upregulated after MG stage. Twenty seven phosphorylation motifs, including 22 pSer motifs and five pThr motifs and 85 kinase including 28 serine/threonine kinases, 14 receptor protein kinases, six mitogen-activated protein kinases, seven calcium-dependent protein kinases, two casein kinases, and some other kinases were quantified. Then the dynamic changes of phosphorylated proteins in ethylene and abscisic acid signaling transduction pathways during fruit development were analyzed. Our results provide a cascade of phosphoproteins and a regulatory network of phosphorylation signals, which help to further understand the mechanism of phosphorylation in pepper fruit development.

Flower transcriptome dynamics during nectary development in pepper (Capsicum annuum L.).

The measurement of gene expression can provide important information about gene function and the molecular basis for developmental processes. We analyzed the transcriptomes at three different developmental stages of pepper flower [sporogenous cell division, stage (B1); pollen mother cell meiosis, stage (B2); and open flower (B3)]. In the cDNA libraries for B1, B2, and B3: 82718, 77061, and 91491 unigenes were assembled, respectively. A total of 34,445 unigene sequences and 128 pathways were annotated by KEGG pathway analysis. Several genes associated with nectar biosynthesis and nectary development were identified, and 8,955, 12,182, and 23,667 DEGs were identified in the B2 vs B1, B3 vs B1, and B3 vs. B2 comparisons. DEGs were involved in various metabolic processes, including flower development, nectar biosynthesis, and nectary development. According to the RNA-seq data, all 13 selected DEGs showed similar expression patterns after q-PCR analysis. Sucrose-phosphatase, galactinol-sucrose galactosyltransferase, and sucrose synthase played very important roles in nectar biosynthesis, and CRABS CLAW could potentially be involved in mediating nectary development. A significant number of simple sequence repeat and single nucleotide polymorphism markers were predicted in the Capsicum annuum sequences. The new results provide valuable genetic information about flower development in pepper.

Integrative Transcriptome and Proteome Analysis Identifies Major Metabolic Pathways Involved in Pepper Fruit Development.

Pepper ( Capsicum annuum L.) fruit development is a complex and genetically programmed process. In this study, we conducted integrative analysis of transcriptome and proteome profiles during pepper fruit development. A total of 23 349 transcripts and 5455 protein groups were identified in four fruit developmental stages of two pepper varieties. The numbers of transcripts and proteins identified were decreased gradually across fruit development, and the most significant changes in transcript and protein levels happened from the mature green (MG) to breaker (Br) stages. Poor correlation between differentially expressed transcript and differentially expressed protein profiles was observed during pepper fruit development. We then analyzed expression profiles of transcripts and proteins involved in cell wall metabolism, and capsanthin, tocopherol, and ascorbate biosynthetic pathways during fruit development, and identified key regulatory proteins in these pathways. We presented a dynamic picture of pepper fruit development via comprehensive analysis of transcriptome and proteome profiles at different fruit developmental stages and in different varieties, revealing the temporal specificity of key protein expression. Our report provides insight into the transcription and translation dynamics of pepper fruit development and a reference for other nonclimacteric species.

Au nanoclusters/porous silica particles nanocomposites as fluorescence enhanced sensors for sensing and mapping of copper(II) in cells.

In this work, we first report Au nanoclusters/porous silica particles nanocomposites as fluorescence enhanced sensors for selective and sensitive detection of Cu (II). As red-emitting GSH-protected Au nanoclusters (Au NCs) were self-assemble into porous silica particles (PSPs) after ultrasonic treatment. As a result, the Au NCs can be immobilized in the nano-channels of PSPs, which leads to the observation of an immobilized induced emission enhancement phenomenon. The photoluminscence (PL) intensity of the nanocomposites can enhance dozens of times compared with Au NCs. As a result, we obtain a novel PL enhanced sensor of Au NCs/PSPs nanocomposites with excellent PL properties. The as-prepared Au NCs/PSPs nanocomposites show good water-solubility, high stability, low toxicity, and exhibit a high PL quenching for reliable, sensitive and selective detection of Cu2+. The limit of detection can reach as low as 1 ppb. What is more, the Au NCs/PSPs nanocomposites also show sensitive detection of Cu2+ in living cells. These properties provide the Au NCs/PSPs nanocomposites with promising PL sensors for Cu2+ detection in various environmental and biological systems.

How calcium ion binding induces the conformational transition of the calmodulin N-terminal domain-an atomic level characterization.

Allostery plays important roles in the regulation of many biological processes, such as signal transduction and transcriptional regulation. Although great advances have been achieved in understanding the allosteric mechanism through experimental and theoretical investigations, the details of the allosteric process are still not clear. Here, using the N-terminal domain of calmodulin (nCaM) as the model protein, we reported the atomic level characterization of the allosteric process induced by Ca2+ binding through extensive and unbiased molecular dynamics simulations. In two trajectories, it was found that Ca2+ first binds to EF-hand 2 and then induces the conformational transformation of nCaM from the Apo to Holo state assisted by second Ca2+ binding to EF-hand 1 completely. The binding order was consistent with a recent experimental result. The simulations also indicated that the two EF-hands changed conformations synergistically and the EF-hand 2 showed an earlier and more gradual conformational transition. Meanwhile, the allosteric process of nCaM triggered by Ca2+ binding might be completed within hundreds of nanoseconds in a two-state-like manner. This was validated by biased simulations, in which the Ca2+ ions were restrained near the binding sites. This work provides the molecular details of the conformational transition of nCaM triggered by Ca2+ binding.

CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression.

Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the regulation of a variety of physiological processes and is involved in early neoplastic development, resulting in poor progression. Hence, suppression of c-Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). It has shown potential efficiency in patients with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a valuable therapeutic option for treating pancreatic adenocarcinoma.