Targeting cyclic hypoxia to prevent malignant progression and therapeutic resistance of cancers

Emerging evidence shows that cyclic hypoxia exists in most solid cancers. It is believed that under cyclic hypoxic conditions cancer cells exhibit more malignant biological behaviors than under chronic hypoxic conditions. In this review, we provide a collection of evidence showing the molecular mechanisms by which cyclic hypoxia induces aggressiveness, malignant progression, and therapeutic resistance in cancers. Moreover, we propose that cyclic hypoxia is responsible for the regulation of cancer stem cells, which possess typical biological characteristics of therapeutic resistance. Based on the present findings, some key factors regulated by cyclic hypoxia may serve as potential targets for the prevention of malignant progression and the treatment of solid cancers. Much research is necessary to gain further insights into the biological aspects of cyclic hypoxia in the development and progression of cancers

CONTACT FINITE ELEMENT ANALYSIS OF JOINT BEARING LAMINATED MEMBRANE COUPLING UNDER COMPOSITE LOADING

In order to explore the stress characteristic of flexible components of the laminated membrane coupling,according to the contact finite element model of laminated group,the stress distributing graphs under the comprehensive load are obtained. Based on the finite element analysis software ANSYS,the geometric model of laminated group is provided,some contacts between the diaphragms are added and methods of applying different loads are proposed. Effects of number of diaphragm on laminated stress are analyzed,and distribution curve of maximum equivalent stress and contact stress on laminated group which from four layers to nine layers are obtained. With laminated group which have nine layers as an example,distribution curves of equivalent stress and contact stress due to different torques,different axial displacements and different angular displacements were obtained. Study shows that Mutative angular displacement is the key effect of laminated stress among various kinds of loading,and the breaking point first occurred around the washer on the lateral diaphragms under the action of composite loading. The compensation capacity,use efficiency of the laminated membrane coupling with joint bearing are greater than the laminated membrane coupling without joint bearing under composite loading

Transcriptomic Analysis Reveals the Correlation between End-of-Day Far Red Light and Chilling Stress in <i>Setaria viridis</i>

Low temperature and end-of-day far-red (EOD-FR) light signaling are two key factors limiting plant production and geographical location worldwide. However, the transcriptional dynamics of EOD-FR light conditions during chilling stress remain poorly understood. Here, we performed a comparative RNA-Seq-based approach to identify differentially expressed genes (DEGs) related to EOD-FR and chilling stress in Setaria viridis. A total of 7911, 324, and 13431 DEGs that responded to low temperature, EOD-FR and these two stresses were detected, respectively. Further DEGs analysis revealed that EOD-FR may enhance cold tolerance in plants by regulating the expression of genes related to cold tolerance. The result of weighted gene coexpression network analysis (WGCNA) using 13431 nonredundant DEGs exhibited 15 different gene network modules. Interestingly, a CO-like transcription factor named BBX2 was highly expressed under EOD-FR or chilling conditions. Furthermore, we could detect more expression levels when EOD-FR and chilling stress co-existed. Our dataset provides a valuable resource for the regulatory network involved in EOD-FR signaling and chilling tolerance in C4 plants

NONLINEAR DYNAMICS ANALYSIS OF DIAPHRAGM COUPLING SYSTEMS WITH ANGULAR MISALIGNMENT

This paper mainly investigated the nonlinear dynamic behavior of diaphragm coupling systems with angular misalignment. First of all, a dynamic model is built according to the characteristic of diaphragm coupling with angular misalignment,whose dynamic differential equation is deduced by the second Lagrange equation. Later,the differential equation is solved by the numerical method. And bifurcation diagram of the systems with the speed changing and the angular misalignment changing are drawn,also the diagrams of displacement response,rotor orbit and phase trajectories under different speeds. And then appropriate nonlinear dynamics are analyzed for these diagrams

Cervical metastasis of gingival carcinoma misdiagnosed as branchiogenic carcinoma, a rare entity - report of a case and review of literature

Abstract Background A cervical cystic mass is associated with a number of pathologies that present with similar symptoms. These conditions are difficult to differentiate using fine-needle aspiration (FNA), ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). Another dilemma in the differential diagnosis of cervical cystic masses is due to the controversies associated with the existence of branchiogenic carcinoma (BC). BC is an extremely rare disease that must be differentiated from other conditions presenting with cervical cystic masses, especially cystic metastasis from occult primary lesions. Case presentation We present a case report of a right cervical cystic metastasis from a significantly small squamous cell carcinoma primary gingival lesion misdiagnosed as BC by histopathology. A 62-year-old female presented with a painless progressively enlarging cervical mass at the anterior edge of the sternocleidomastoid muscle in the right submandibular region. Preoperative MRI and US revealed a well-defined cystic round mass. Postoperative histological examination indicated BC. Positron emission tomography/computed tomography (PET/CT) revealed high 18F–FDG (18F 2-fluoro-2-deoxy-D-glucose) uptake in surgical regions with a SUV (standard uptake value) max 4.0 and ipsilateral nasopharynx with a SUVmax 4.4, without any distant metastasis. Pathologic results revealed nasopharyngeal lymphadenosis. Considering the low incidence of BC and the limitation of diagnosis in one institution, the patient was referred to another hospital. Physical examination detected a significantly small neoplasm (~3 mm diameter) in the right lower gingiva. Histopathological examination of the neoplasm revealed a well-differentiated squamous cell carcinoma. Surgery, including a partial mandibulectomy and modified neck dissection (neck level I–V and submental lymph nodes) were undertaken. Postoperative histopathological results revealed a well-differentiated squamous cell carcinoma of right lower gingiva and two metastatic lymph nodes in the 18 lymph nodes of level II. A month later, recurrence occurred in the right cervical level II. The patient was placed on postoperative concurrent chemo-radiotherapy and supportive care. The patient suffered from cachexia and survived for only six months after surgery. Conclusions In cases of cervical cystic masses that appear after the age of 40, clinicians should bear in mind that occult primary lesions should be excluded and examination of the gingiva should be undertaken. PET/CT has a limited role in identifying small occult primary lesions and a comprehensive physical examination must be carefully performed

Image3_Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration.TIF

Liver cirrhosis is one of the most common cause of death in the world. The progress of liver cirrhosis involves health, liver cirrhosis and liver cancer, leading to great challenges in the diagnosis of the disease. Drug targets, which could be obtained conveniently, can help clinicians improve prognosis and treatment. Liver cirrhosis is associated with serum calcium levels. And studies reported Tanshinone IIA plays a therapeutic role in liver injury through activating calcium-dependent apoptosis. In this study, we explored the diagnostic key targets of Tanshinone IIA in liver cirrhosis through exploration of comprehensive dataset including health, liver cirrhosis and liver cancer patients. The unsupervised consensus clustering algorithm identified 3 novel subtypes in which differentially expressed genes (DEGs) between both subtypes were found by pairwise comparison. Then, 4 key drug targets of Tanshinone IIA were determined through the intersection of these DEGs. The diagnostic performance of target genes was assessed and further verified in the external dataset. We found that the 4 key drug targets could be used as effective diagnostic biomarkers. Then the immune scores in the high and low expression groups of target genes were estimated to identify significantly expressed immune cells. In addition, the immune infiltration of high and low target gene expression groups in several immune cells were significantly different. The findings suggest that 4 key drug targets may be a simple and useful diagnostic tool for predicting patients with cirrhosis. We further studied the carcinogenesis role of AKR1C3 and TPX2 in vitro. Both mRNA and protein expression in hepatoma carcinoma cells was detected using qRT-PCR and Western blot. And the knockdown of AKR1C3 and TPX2 significantly suppressed cell proliferation, migration and invasion.</p

Image2_Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration.TIF

Liver cirrhosis is one of the most common cause of death in the world. The progress of liver cirrhosis involves health, liver cirrhosis and liver cancer, leading to great challenges in the diagnosis of the disease. Drug targets, which could be obtained conveniently, can help clinicians improve prognosis and treatment. Liver cirrhosis is associated with serum calcium levels. And studies reported Tanshinone IIA plays a therapeutic role in liver injury through activating calcium-dependent apoptosis. In this study, we explored the diagnostic key targets of Tanshinone IIA in liver cirrhosis through exploration of comprehensive dataset including health, liver cirrhosis and liver cancer patients. The unsupervised consensus clustering algorithm identified 3 novel subtypes in which differentially expressed genes (DEGs) between both subtypes were found by pairwise comparison. Then, 4 key drug targets of Tanshinone IIA were determined through the intersection of these DEGs. The diagnostic performance of target genes was assessed and further verified in the external dataset. We found that the 4 key drug targets could be used as effective diagnostic biomarkers. Then the immune scores in the high and low expression groups of target genes were estimated to identify significantly expressed immune cells. In addition, the immune infiltration of high and low target gene expression groups in several immune cells were significantly different. The findings suggest that 4 key drug targets may be a simple and useful diagnostic tool for predicting patients with cirrhosis. We further studied the carcinogenesis role of AKR1C3 and TPX2 in vitro. Both mRNA and protein expression in hepatoma carcinoma cells was detected using qRT-PCR and Western blot. And the knockdown of AKR1C3 and TPX2 significantly suppressed cell proliferation, migration and invasion.</p