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| 1 | Heat shock protein 47 promotes tumor survival and therapy resistance by modulating AKT signaling via PHLPP1 in colorectal cancer显示文摘Objective:Heat shock protein 47(HSP47)is a collagen-specific molecular chaperone that facilitates collagen maturation.Its role in cancer remains largely unknown.In this study,we investigated the roles o f HSP47 in colorectal cancer(CRC)and therapy resistance.Methods:Expression o f HSP47 in CRC tissues was examined(1)in paired human CRC/adjacent normal tissues,using real time quantitative reverse transcription polymerase chain reaction(qRT-PCR),The Cancer Genome Atlas(TCGA)database,and 22 independent m icroarray databases(curated CRC).In vitro studies on several CRC cell lines(H C T 116,RKO and C C L228)with modulated HSP47 expression were conducted to assess cell viability and apoptosis(TU N EL assay and caspase-3/-7)during exposure to chemotherapy.AKT signaling and co-imm unoprecipitation studies were performed to examine HSP47 and PHLPP1 interaction.In vivo studies using tumor xenografts were conducted to assess the effects of HSP47 modulation on tum or growth and therapy response.Results:HSP47 was upregulated in CRC and was associated with poor prognosis in individuals with CRC.In vitro,HSP47 overexpression supported the survival of CRC cells,whereas its knockdown sensitized cells to 5-fluorouracil(5-FU).HSP47 promoted survival by inhibiting apoptosis,enhancing AKT phosphorylation,and decreasing expression of the AKT-specific phosphatase PHLPP1 when cells were exposed to chemotherapy.These effects were partly results of the interaction between HSP47 and PHLPP1,which decreased PHLPP1 stability and led to more persistent AKT activity.In vivoy HSP47 supported tumor growth despite 5-FU treatment.Conclusions:HSP47 supports the growth of CRC tumors and suppresses the efficacy of chemotherapy via modulation of AKT signaling. | Yijye Chern Peter Zhang Hyelim Ju Isabella T.Tai | 2020 | Cancer Biology & Medicine2020，17，2： | 3 |
| 2 | Self‐Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN‐PT Piezoelectric Energy Harvester显示文摘 | Geon‐Tae Hwang Hyewon Park Jeong‐Ho Lee SeKwon Oh Kwi‐Il Park Myunghwan Byun Hyelim Park Gun Ahn Chang Kyu Jeong Kwangsoo No HyukSang Kwon Sang‐Goo Lee Boyoung Joung Keon Jae Lee | 2014 | Adv. Mater2014，，28： | 1 |
| 3 | COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm显示文摘Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is unknown.Here,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19.Intriguingly,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity.We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients.Using an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages.These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients. | Wonhwa Lee June Hong Ahn Hee Ho Park Hong Nam Kim Hyelim Kim Youngbum Yoo Hyosoo Shin Kyung Soo Hong Jong Geol Jang Chun Gwon Park Eun Young Choi Jong-Sup Bae Young-Kyo Seo | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 4 | Perception of unrelated microbe-associated molecular patterns triggers conserved yet variable physiological and transcriptional changes in Brassica rapa ssp.pekinensis显示文摘Pattern-triggered immunity(PTI)includes the different transcriptional and physiological responses that enable plants to ward off microbial invasion.Surface-localized pattern-recognition receptors(PRRs)recognize conserved microbeassociated molecular patterns(MAMPs)and initiate a branched signaling cascade that culminate in an effective restriction of pathogen growth.In the model species Arabidopsis thaliana,early PTI events triggered by different PRRs are broadly conserved although their nature or intensity is dependent on the origin and features of the detected MAMP.In order to provide a functional basis for disease resistance in leafy vegetable crops,we surveyed the conservation of PTI events in Brassica rapa ssp.pekinensis.We identified the PRR homologs present in B.rapa genome and found that only one of the two copies of the bacterial Elongation factor-Tu receptor(EFR)might function.We also characterized the extent and unexpected specificity of the transcriptional changes occurring when B.rapa seedlings are treated with two unrelated MAMPs,the bacterial flagellin flg22 peptide and the fungal cell wall component chitin.Finally,using a MAMP-induced protection assay,we could show that bacterial and fungal MAMPs elicit a robust immunity in B.rapa,despite significant differences in the kinetic and amplitude of the early signaling events.Our data support the relevance of PTI for crop protection and highlight specific functional target for disease resistance breeding in Brassica crops. | Wanhui Kim Maxim Prokchorchik Yonghua Tian Seulgi Kim Hyelim Jeon Cécile Segonzac | 2020 | Horticulture Research2020，7，1： | 0 |
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