Pancreatic cancer is a highly aggressive cancer with an exceedingly low rate of response to treatments, which calls for comprehensive molecular characterization of pancreatic cancer cell lines ...(PCCLs). We screened multi-layer molecular data of 36 PCCLs, including gene mutation, gene expression, microRNA (miRNA) expression, and protein profiles. Our comparative analysis of genomic mutations found that PCCLs recapitulated genomic alterations of the primary tumor and suggested potential therapeutic strategies for clinical interventions. The panel of 36 PCCLs was classified into 2 subgroups based on transcriptomic mRNA expression, wherein the C1 subgroup was characterized with differentiation, whereas C2 cell lines were featured with immunity, angiogenesis, epidermis, and proliferation. Transcriptomic classification was further recapitulated by miRNA and protein expression. Additionally, the differential proteins between C1 and C2 subgroups were prominently involved in epidermal growth factor receptor (EGFR) signaling, phosphatidylinositol 3-kinase (PI3K) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways. Tumor samples from different subgroups exhibited distinct infiltration of CD4 naive cells and monocytes. Remarkably, patients in subgroups C1 showed longer survival, whereas those in C2 had worse clinical outcome. Further integrative analysis revealed that temozolomide and NVP-TAE684 showed higher sensitivity in the C1 subgroup, whereas the C2 cell lines were more sensitive to SR1001 and SRT-1720. Our results also showed that PCCLs with mutations in CDKN2A, TP53, and SMAD4 were more sensitive to certain anti-cancer drugs. Our integrative analysis identified molecular features of pancreatic cancer that were associated with clinical significance and drug sensitivity, providing potentially effective strategies for precision treatments of patients with pancreatic cancer.
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This study provides a comprehensive characterization of multiple pancreatic cancer cell lines, which are divided into 2 subgroups that showed therapeutic differences.
Air route planning system is the core of antisubmarine call-search mission which is carried out by an ASW helicopter, and the efficiency of mission completion is decided by the algorithm adopted. ...Considering actual army training and combat, this paper analyses the basic elements of responding-antisubmarine air route planning system systematically, constitutes assessment index of air route planning system, presents the constraint conditions which should be considered by the system and carries out simulation calculation by ant colony algorithm. Finally, this paper summarizes the applicable circumstances of responding-antisubmarine air route planning methods based on ant colony algorithm, which will be of great value to improve army combat and training efficiency.
Oxidative stress is an important pathogenic factor in various hepatic diseases. Nuclear factor-erythroid 2-related factor-2 (Nrf2), which coordinates the expression of an array of antioxidant and ...detoxifying genes, has been proposed as a potential target for prevention and treatment of liver disease. Dibenzoylmethane (DBM) is a minor ingredient in licorice that activates Nrf2 and prevents various cancers and oxidative damage. In the present study, the mechanisms by which DBM activates Nrf2 signaling were delineated, and its protective effect against carbon tetrachloride (CCl
4
)-induced liver injury was examined. DBM potently induced the expression of HO-1 in cells and in the livers of mice, but this induction was diminished in Nrf2-deficient mice and cells. Overexpression of Nrf2 enhanced DBM-induced HO-1 expression, while overexpression of a dominant-negative fragment of Nrf2 inhibited this induction. DBM treatment resulted in dissociation from Keap1 and nuclear translocation of Nrf2. Moreover, DBM activated Akt/protein kinase B, mitogen-activated protein kinases, and AMP-activated protein kinase and increased intracellular calcium levels. Inhibition of JNK, AMPK, or intracellular calcium signaling significantly suppressed the induction of HO-1 expression by DBM. Finally, DBM treatment significantly inhibited CCl
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-induced acute liver injury in wild-type but not in Nrf2-deficient mice. Taken together, our results revealed the mechanisms by which DBM activates Nrf2 and induces HO-1 expression, and provide molecular basis for the design and development of DBM and its derivatives for prevention or treatment of liver diseases by targeting Nrf2.
GaTe has recently attracted significant interest due to its direct bandgap and unique phase structure, which makes it a good candidate for optoelectronics. However, the controllable growth of ...large‐sized monolayer and few‐layer GaTe with tunable phase structures remains a great challenge. Here the controlled growth of large‐sized GaTe with high quality, chemical uniformity, and good reproducibility is achieved through liquid‐metal‐assisted chemical vapor deposition method. By using liquid Ga, the rapid growth of 2D GaTe flakes with high phase‐selectivity can be obtained due to its reduced reaction temperature. In addition, the method is used to synthesize many Ga‐based 2D materials and their alloys, showing good universality. Raman spectra suggest that the as‐grown GaTe own a relatively weak van der Waals interaction, where monoclinic GaTe displays highly‐anisotropic optical properties. Furthermore, a p‐n junction photodetector is fabricated using GaTe as a p‐type semiconductor and 2D MoSe2 as a typical n‐type semiconductor. The GaTe/MoSe2 heterostructure photodetector exhibits large photoresponsivity of 671.52 A W−1 and high photo‐detectivity of 1.48 × 1010 Jones under illumination, owing to the enhanced light absorption and good quality of as‐grown GaTe. These results indicate that 2D GaTe is a promising candidate for electronic and photoelectronic devices.
A liquid‐metal‐assisted chemical vapor deposition method is proposed to achieve the controlled growth of large‐sized monolayer and few‐layer GaTe with high quality, high phase‐selectivity, chemical uniformity, and good reproducibility. The method can be extended to grow Ga‐based 2D materials and their alloys, including GaSe, GaS, GaTe1‐xSex, and even InSe, which significantly speed up the technological applications of 2D materials.
Implantable biomaterials are widely used in bone tissue engineering, but little is still known about how they initiate early immune recognition and the initial dynamics. Herein, the early immune ...recognition and subsequent osteoinduction of biphasic calcium phosphate (BCP) after implantation to the protein adsorption behavior is attributed. By liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, the biomaterial-related molecular patterns (BAMPs) formed after BCP implantation are mapped, dominated by the highly expressed extracellular matrix protein fibronectin (Fn) and the high mobility group box 1 (HMGB1). Molecular dynamics simulations show that Fn has the ability to bind more readily to the BCP surface than HMGB1. The preferential binding of Fn provides a higher adsorption energy for HMGB1. Furthermore, multiple hydrogen bonding sites between HMGB1 and Fn are demonstrated using a molecular docking approach. Ultimately, the formation of BAMPs through HMGB1 antagonist glycyrrhizic acid (GA), resulting in impaired immune recognition of myeloid differentiation factor 88 (MYD88) mediated dendritic cells (DCs) and macrophages (Mφs), as well as failed osteoinduction processes is obstructed. This study introduces a mechanism for early immune recognition of implant materials based on protein adsorption, providing perspectives for future design and application of tissue engineering materials.
As an accurate, safe, and effective noninvasive examination method, imaging examination has been widely used in the diagnosis and differential diagnosis of focal liver lesions. Enhanced ...ultrasonography (CEUS), enhanced CT (CECT), and enhanced magnetic resonance imaging (CEMRI) are the most commonly used enhanced imaging methods in clinical practice, all of which can accurately determine the nature of liver lesions. The purpose of this paper is to study the application of contrast-enhanced ultrasound and magnetic resonance enhancement in cancer diagnosis based on the Internet of Things medical system. The basic clinical data, CEUS, and enhanced CT/MRI findings of 120 CHC patients were retrospectively analyzed. The clinicopathological features of CHC patients were investigated by contrast-enhanced ultrasonography and CT/MRI enhanced mode. The diagnostic value of contrast-enhanced ultrasound and enhanced CT/MRI combined with tumor markers in CHC was analyzed. The experimental results showed that the sensitivities of CEUS, enhanced MRI, and their combination in diagnosing CHC were 72.44%, 81.56%, and 93.78%, respectively. This experiment has an important value in the diagnosis of primary liver cancer.
Ferroptosis is a predominant contributor to graft kidney ischemia‒reperfusion injury (IRI), resulting in delayed graft function (DGF). However, much less is known about the early predicting ...biomarkers and therapeutic targets of DGF, especially aiming at ferroptosis. Here, we propose a precise predicting model for DGF, relying on the Akirin1 level in extracellular vesicles (EVs) derived from recipient urine 48 h after kidney transplant. In addition, we decipher a new molecular mechanism whereby Akirin1 induces ferroptosis by strengthening TP53‐mediated suppression of SLC7A11 during the graft kidney IRI process, that is, Akirin1 activates the EGR1/TP53 axis and inhibits MDM2‐mediated TP53 ubiquitination, accordingly upregulating TP53 in two ways. Meanwhile, we present the first evidence that miR‐136‐5p enriched in EVs secreted by human umbilical cord mesenchymal stem cells (UM‐EVs) confers robust protection against ferroptosis and graft kidney IRI by targeted inhibition of Akirin1 but knockout of miR‐136‐5p in UM sharply mitigates the protection of UM‐EVs. The functional and mechanistic regulation of Akirin1 is further corroborated in an allograft kidney transplant model in wild‐type and Akirin1‐knockout mice. In summary, these findings suggest that Akirin1, which prominently induces ferroptosis, is a pivotal biomarker and target for early diagnosis and treatment of graft kidney IRI and DGF after kidney transplant.
Proposed model for how UM‐EVs mitigate ferroptosis and protect against graft kidney IRI. Akirin1, which is prominently elevated in the kidney IRI process, promotes EGR1‐mediated TP53 expression and suppresses MDM2‐mediated TP53 ubiquitination and degradation, accordingly upregulating TP53 in two ways. This further enhances TP53‐mediated suppression of SLC7A11 and thus facilitates ferroptosis. MiR‐136‐5p enriched in UM‐EVs protects against ferroptosis and graft kidney IRI by inhibiting Akirin1.
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