Transcriptional suppression of breast cancer resistance protein (BCRP) by wild-type p53 through the NF-κB pathway in MCF-7 cells

AbstractBreast cancer resistance protein (BCRP) has been shown to confer multidrug resistance, but the mechanisms of its regulation are poorly understood. Here, we investigate the effects of wild-type and mutant p53, and nuclear factor kappa-B (NF-κB) (p50) on BCRP promoter activity in MCF-7 cells. Our results demonstrated that wild-type p53 markedly suppressed BCRP activity and enhanced the chemosensitivity of cells to mitoxantrone, whereas mutant p53 had little inhibitory effect. After inhibition of NF-κB, similar results were obtained. Following knockdown of endogenous p53, BCRP and p50 expressions were increased, and the chemosensitivity of the cells to mitoxantrone was decreased. We conclude that wild-type p53 acts as a negative regulator of BCRP gene transcription

Activation of JNK Signaling Mediates Connective Tissue Growth Factor Expression and Scar Formation in Corneal Wound Healing

Connective Tissue Growth Factor (CTGF) and Transforming growth factor-β1 (TGF-β1) are key growth factors in regulating corneal scarring. Although CTGF was induced by TGF-β1 and mediated many of fibroproliferative effects of TGF-β1, the signaling pathway for CTGF production in corneal scarring remains to be clarified. In the present study, we firstly investigated the effects of c-Jun N-terminal kinase (JNK) on CTGF expression induce by TGF-β1 in Telomerase-immortalized human cornea stroma fibroblasts (THSF). Then, we created penetrating corneal wound model and determined the effect of JNK in the pathogenesis of corneal scarring. TGF-β1 activated MAPK pathways in THSF cells. JNK inhibitor significantly inhibited CTGF, fibronectin and collagen I expression induced by TGF-β1 in THSF. In corneal wound healing, the JNK inhibitor significantly inhibited CTGF expression, markedly improved the architecture of corneal stroma and reduced corneal scar formation, but did not have a measurable impact on corneal wound healing in vivo. Our results indicate that JNK mediates the expression of CTGF and corneal scarring in corneal wound healing, and might be considered as specific targets of drug therapy for corneal scarring

Towards Effective Management: Toxicity, Causal Mechanism and Controlling Strategy of Toxic Rangeland Weeds in Western China

Toxic rangeland weeds (TRWs) pose a great threat to animal husbandry. Currently, an estimated 33 million hectares of pasture (10%) in western China is infested by a variety of toxic weeds, including Stellera chamaejasme, Oxytropis spp., Astragalus spp., Achnatherum inebrians. The spread of these toxic weeds results in huge annual economic losses of more than $2.4 billion USD (direct and indirect). A combination of ecology, molecular biology, biochemistry and field practise methods will be used to identify and evaluate TRWs, explore the mechanism of toxicity, and more importantly, understand the causal mechanism by which TRWs flourish. The knowledge will underpin the development of effective management strategies

RNA-Sequencing Reveals Global Transcriptomic Changes in \u3cem\u3eNicotiana tabacum\u3c/em\u3e Responding to Topping and Treatment of Axillary-Shoot Control Chemicals

Removal of terminal buds (topping) and control of the formation of axillary shoots (suckers) are common agronomic practices that significantly impact the yield and quality of various crop plants. Application of chemicals (suckercides) to plants following topping is an effective method for sucker control. However, our current knowledge of the influence of topping, and subsequent suckercide applications, to gene expression is limited. We analyzed the differential gene expression using RNA-sequencing in tobacco (Nicotiana tabacum) that are topped, or treated after topping by two different suckercides, the contact-localized-systemic, Flupro® (FP), and contact, Off-Shoot-T®. Among the differentially expressed genes (DEGs), 179 were identified as common to all three conditions. DEGs, largely related to wounding, phytohormone metabolism and secondary metabolite biosynthesis, exhibited significant upregulation following topping, and downregulation after suckercide treatments. DEGs related to photosynthetic processes were repressed following topping and suckercide treatments. Moreover, topping and FP-treatment affect the expression of auxin and cytokinin signaling pathway genes that are possibly involved in axillary shoot formation. Our results provide insights into the global change of plant gene expression in response to topping and suckercide treatments. The regulatory elements of topping-inducible genes are potentially useful for the development of a chemical-free sucker control system

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background: Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects. Methodology/Principal Findings: aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%). Conclusions/Significance: It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects

Process, microstructure and mechanical properties

Funding Information: This work was supported by National Natural Science Foundation of China (Grant No. 51875168/52002112 ), Natural Science Foundation of Hebei Province (Grant No. E2019208089 ) and “Three-Three-Three Talent Project” Foundation of Hebei Province ( C20221022 ). Sichuan Province Science Funding for Distinguished Young Scholars ( 3NSFJQ0064 ). JPO acknowledges funding by national funds from FCT – Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020. Science and Technology Research Project of Colleges and Universities in Hebei Province (Grant No. BJK2022020 ). Publisher Copyright: © 2023 The AuthorsAiming to decouple the inherent relationship between mass transfer and heat transfer in traditional arc-based directed energy deposition, a novel heterogeneous multi-wire indirect arc directed energy deposition (DED) has been developed for in-situ synthesis of Al-Zn-Mg-Cu alloy components. Multi-wires (Al-Cu and Al-Mg) with a bypassing Zn wire have been used to replace the traditional homogeneous twin-wires. The process, microstructure and mechanical properties of the deposited Al-Zn-Mg-Cu alloy components obtained by multi-wire indirect arc DED were investigated. The results indicate that the wire feeding speed, current and angle between the two wires have a significant influence on the multi-wire indirect arc DED process. When the current was 200 A, the different wire feeding speeds could be used for both wires and the angle between them was 90°. The resulting indirect arc presented a ‘heart’ shape and allowed to obtain an Al-5.7Zn-3.4Mg-1.6Cu (wt%) alloy with a high deposition rate of 5.1 kg/h. The Al-5.7Zn-3.4Mg-1.6Cu alloy is mainly composed of α-Al, S (Al2CuMg), η (Mg (Al, Zn, Cu)2) and η′ phases. The composition and phases are in accordance with the 7xxx series aluminum alloys. The microstructure is dominated by columnar and equiaxed grains, and it has obvious periodic distribution along the building direction, which is related to the process thermal cycle. Fine second phases η′ are observed to precipitate during the manufacturing process. Furthermore, the average hardness, ultimate tensile strength and elongation of the fabricated material are 98.6 HV, 243.9 MPa and 5.9%, respectively. These mechanical properties are higher than those of as-cast 7050 aluminum alloy, thus showing the potential of this new process variant to fabricate high strength Al alloys in the as-deposited state. The fracture morphology exhibit features mainly associated to a ductile-like fracture, accompanied by some transgranular and partial cleavage fracture characteristics. This novel multi-wire indirect arc DED provides a new choice for arc-based directed energy deposition of Al-Zn-Mg-Cu alloys and shows great potential for the in-situ synthesis of other high-performance alloys.publishersversionpublishe

Clinical Evaluation of High-risk HR-HPV E6/E7 mRNA Detection during Pregnancy

BackgroundIt is necessary to differentiate high-risk human papillomavirus (HR-HPV) infection and cervical lesions during pregnancy using an effective measure, so as to guide personalized diagnosis and treatment and to reduce unnecessary invasive examinations during pregnancy.ObjectiveTo assess the value of HR-HPV E6/E7 mRNA detection in differentiating HR-HPV infection and cervical lesions during pregnancy by comparing efficacy between it and HR-HPV DNA testing.MethodsParticipants were healthy women with singleton pregnancy (20-45-years old) selected from Department of Obstetrics and Gynecology of Capital Medical University Xuanwu Hospital during January 2016 to January 2019. All had file creation and underwent regular prenatal examination, and those with abnormal liquid-based cytology and HR-HPV DNA testing results further underwent colposcopy with biopsy taken for pathological examination (serving as a gold standard) , and performed HR-HPV E6/E7 mRNA detection in cervical exfoliated cells collected as samples. Pathologically detected CIN Ⅱand Ⅲ were defined as high-grade cervical lesions.ResultsOf the 1 058 participants, 118 had cytological abnormalities and/or HPV 16 and 18 infections, and 84 of them consented to perform colposcopy with biopsy pathological results successfully obtained. The prevalence of HR-HPV E6/E7 mRNA positivity was lower than that of HR-HPV DNA positivity in women with CINⅠ, normal cervical epithelium or cervicitis detected by pathological examination (P<0.05) . In contrast, the prevalence of HR-HPV E6/E7 mRNA positivity was similar to that of HR-HPV DNA positivity in those with CINⅡ and Ⅲ detected by pathological examination without statistical difference (P>0.05) . In predicting CINⅡ and Ⅲ, the HR-HPV DNA testing had a sensitivity of 89.7% (26/29) , a specificity of 21.8% (12/55) , a positive predictive value of 37.1% (26/69) , and a negative predictive value of 75.0% (12/29) , and the HR-HPV E6/E7 mRNA detection had a sensitivity of 65.5% (19/29) , a specificity of 54.5% (25/55) , a positive predictive value of 43.0% (19/44) , and a negative predictive value 75.0% (25/40) . McNemar's test revealed that HR-HPV E6/E7 mRNA detection had a lower sensitivity but a higher specificity than HR-HPV DNA testing in diagnosing CINⅡ and Ⅲ (P<0.05) .ConclusionHR-HPV E6/E7 mRNA detection may have an increased specificity in diagnosing CINⅡandⅢ than HR-HPV DNA testing, so it may be used in HR-HPV positive cases for differentiating HR-HPV infections and cervical lesions to avoid unnecessary invasive examinations during pregnancy