MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis

Gan Junqing,Liu Shan,Zhang Yu,He Liangzi,Bai Lu,Liao Ran,Zhao Juan,Guo Madi,Jiang Wei,Li Jiade,Li Qi,Mu Guannan,Wu Yangjiazi,Wang Xinling,Zhang Xingli,Zhou Dan,Lv Huimin,Wang Zhengfeng,Zhang Yanqiao,Q 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.

Microfluidic continuous flow synthesis of 1,5-ditosyl-1,5-diazocane- 3,7-dione using response surface methodology

Yang Zou,Tao Zhang,Guannan Wang,Mengwen Zhou,Yabo Xiong,Shaoyun Huang,Houbin Li,Xinghai Liu 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.82 No.-

3,3,7,7-tetrakis(difluoroamino) octahydro-1,5-dinitro-1,5-diazocine (HNFX) is a high-density energeticoxidizer with four difluoroamino groups (-NF2). In this study, 1,5-ditosyl-1,5-diazocane-3,7-dione, as animportant intermediate for synthesis of HNFX, was successfully synthesized using Swern oxidation in atraditional batch reactor and a continuousflow microreactor, respectively. 1,5-dotosyl-1,5-diazocane-3,7-dione was characterized by HPLC, FTIR, 1H NMR, 13C NMR, Mass spectrometry, and X-ray crystaldiffraction. Compared with the traditional batch reactor, the microreactor showed several advantages,including less reaction time, milder reaction temperature, higher yield and selectivity for 1,5-ditosyl-1,5-diazocane-3,7-dione. Moreover, the microreactor could ensure the safer and large-scale industrialproduction of 1,5-ditosyl-1,5-diazocane-3,7-dione. However, some solids produced in Swern oxidationwhich might block the channels (diameter of 0.3 mm) in the microreactor. To overcome the challenges,the experimental device was modified to suit for Swern oxidation, contributing to wider application ofthe microreactor. Besides, response surface methodology (RSM) was introduced and an appropriatemathematical model was built to optimize experimental conditions. The optimum experimentalparameters were recommended as 7.8 C for the reaction temperature, 7.7 mL/min for theflow rate, and6% for the concentration of oxalyl chloride. The actual yield of 1,5-ditosyl-1,5-diazocane-3,7-dione was89.7%, which was in great agreement with the highest predicted yield (90.1%).

Abnormal Precursory Information Analysis of the Infrared Radiation Temperature (IRT) before Sandstone Failure

Zhanping Song,Qiang Zhang,Yuwei Zhang,Junbao Wang,Shengyuan Fan,Guannan Zhou 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.11

To study the abnormal precursory information of rock before failure, uniaxial compression tests were carried out on sandstone specimens; meanwhile, the infrared thermal camera was utilized to monitor the infrared radiation temperature (IRT) variation of the specimen surface synchronously during failure process. The test results show that with the increases of strain, the average infrared radiation temperature (AIRT) decreased gradually; when strain raises to a certain degree, the AIRT increased abruptly; thereafter, the AIRT decreased gradually with increasing strain. Therefore, the mutation point of AIRT can be regarded as the abnormal precursory information of sandstone before failure. Through analysis, the average stress at the abnormal point was 79.93% of the uniaxial compression strength of the sandstone specimens tested in this paper, and the average strain at this point was 0.9%. In addition, due to the end effect, the IRT field distribution of the sandstone specimen surface presented a decreasing tendency from top to bottom at the initial loading stage. As strain increases, the IRT field distribution tended to be high in middle and low in two ends. Closing to failure, a Y-shaped high-temperature band caused by the shear failure of the specimen appeared in the infrared thermal image. After comparison, the position of the Y-sharped high-temperature band is basically corresponding to the actually failure position of the specimen. With the increases of strain, the IRT distribution ranges decreased and the IRT frequency distribution histogram form gradually approached to the normal distribution.

Achieving Ultra-High-Strength and Good Ductility of the ZK60 Alloy Sheet by High Strain-Rate Rolling

Songhui Wang,Wencong Zhang,Jianlei Yang,Xeuyan Jiao,Jinqi Pan,Guannan Chu,Xiangyu Dai 대한금속·재료학회 2023 METALS AND MATERIALS International Vol.29 No.4

A superior combination of the ultra-high tensile strength (~ 419.9 MPa), the yield strength (~ 376.9 MPa) and the elongation(~ 14.8%) ZK60 sheet was successfully achieved by high-strain rate rolling. The ultrahigh strength was attributed to theuniform ultrafine-grained structure. The excellent ductility was ascribed to the ultrafine grains, low dislocation density andweakened basal texture in the final structure.

First-principles investigation of V2CSe2 MXene as a potential anode material for non-lithium metal ion batteries

Wang Yanzong,Ma Yihan,Zhang Qinfang,Huang Rui,Gao Benling,Li Zhongwen,Li Guannan,Liang Feng 한국물리학회 2022 Current Applied Physics Vol.41 No.-

The electrochemical performances of the V2CSe2 MXene as anode materials for Na, K, Mg, Ca, and Al-ion batteries have been systematically investigated by the first-principles method. The adsorption energies of metal atoms show that Na, K, and Ca atoms can effectively adsorb on the V2CSe2, except for Mg and Al atoms. The large diffusion constants for Na, K, and Ca atoms calculated by the diffusion energy barriers (0.098 eV for Na, 0.066 eV for Ca, and 0.24 eV for Ca) indicate the high mobility on the V2CSe2 surface. Significantly, the maximum theoretical capacities of V2CSe2 reach up to 394.12 mA h/g for Na and Ca ions. Furthermore, the low average open-circuit voltage (OCV) (0.150 V for Na, 0.175 V for K, and 0.072 V for Ca) indicates the V2CSe2 is a suitable anode material. These results provide fundamental guidance for the V2CSe2 monolayer as anode materials of non-lithium metal-ion batteries.

Transcriptomic view of survival during early seedling growth of the extremophyte <i>Haloxylon ammodendron</i>

Fan, Ligang,Wang, Guannan,Hu, Wei,Pantha, Pramod,Tran, Kieu-Nga,Zhang, Hua,An, Lizhe,Dassanayake, Maheshi,Qiu, Quan-Sheng Elsevier 2018 Vol. No.

<P><B>Abstract</B></P> <P>Seedling establishment in an extreme environment requires an integrated genomic and physiological response to survive multiple abiotic stresses. The extremophyte, <I>Haloxylon ammodendron</I> is a pioneer species capable of colonizing temperate desert sand dunes. We investigated the induced and basal transcriptomes in <I>H. ammodendron</I> under water-deficit stress during early seedling establishment. We find that not only drought-responsive genes, but multiple genes in pathways associated with salt, osmotic, cold, UV, and high-light stresses were induced, suggesting an altered regulatory stress response system. Additionally, <I>H. ammodendron</I> exhibited enhanced biotic stress tolerance by down-regulation of genes that were generally up-regulated during pathogen entry in susceptible plants. By comparing the <I>H. ammodendron</I> basal transcriptome to six closely related transcriptomes in Amaranthaceae, we detected enriched basal level transcripts in <I>H. ammodendron</I> that shows preadaptation to abiotic stress and pathogens. We found transcripts that were generally maintained at low levels and some induced only under abiotic stress in the stress-sensitive model, <I>Arabidopsis thaliana</I> to be highly expressed under basal conditions in the Amaranthaceae transcriptomes including <I>H. ammodendron</I>. <I>H. ammodendron</I> shows coordinated expression of genes that regulate stress tolerance and seedling development resource allocation to support survival against multiple stresses in a sand dune dominated temperate desert environment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We report the transcriptomic signals of <I>H. ammodendron</I> in response to drought that contribute to plant survival. </LI> <LI> We highlight the transcriptional and biological processes for the survival of <I>H. ammodendron</I> at early developmental stage. </LI> <LI> We find abundant orthologs in extremophytes that are rare in Arabidopsis. </LI> <LI> These orthologs provide novel candidates to discover networks naturally selected as adaptations to environmental stresses. </LI> </UL> </P>

Visual deprivation modifies oscillatory activity in visual and auditory centers

Ping Pan,You Zhou,Fanghao Fang,Guannan Zhang,Yonghua Ji 한국통합생물학회 2018 Animal cells and systems Vol.22 No.3

Loss of vision may enhance the capabilities of auditory perception, but the mechanisms mediating these changes remain elusive. Here, visual deprivation in rats resulted in altered oscillatory activities, which appeared to be the result of a common mechanism underlying neuronal assembly formation in visual and auditory centers. The power of high-frequency β and γ oscillations in V1 (the primary visual cortex) and β oscillations in the LGN (lateral geniculate nucleus) was increased after one week of visual deprivation. Meanwhile, the power of β oscillations in A1 (the primary auditory cortex) and the power of β and γ oscillations in the MGB (medial geniculate body) were also enhanced in the absence of visual input. Furthermore, nerve tracing revealed a bidirectional nerve fiber connection between V1 and A1 cortices, which might be involved in transmitting auditory information to the visual cortex, contributing to enhanced auditory perception after visual deprivation. These results may facilitate the better understanding of multisensory cross-modal plasticity.

A Chaperone Function of NO CATALASE ACTIVITY1 Is Required to Maintain Catalase Activity and for Multiple Stress Responses in Arabidopsis

Li, Jing,Liu, Juntao,Wang, Guoqiang,Cha, Joon-Yung,Li, Guannan,Chen, She,Li, Zhen,Guo, Jinghua,Zhang, Caiguo,Yang, Yongqing,Kim, Woe-Yeon,Yun, Dae-Jin,Schumaker, Karen S.,Chen, Zhongzhou,Guo, Yan American Society of Plant Biologists 2015 The Plant cell Vol.27 No.3

<P>Arabidopsis protein NCA1 interacts with catalases in the cytosol and increases catalase activity through maintaining catalase folding state, which is required for stress responses.</P><P>Catalases are key regulators of reactive oxygen species homeostasis in plant cells. However, the regulation of catalase activity is not well understood. In this study, we isolated an <I>Arabidopsis thaliana</I> mutant, <I>no catalase activity1-3</I> (<I>nca1-3</I>) that is hypersensitive to many abiotic stress treatments. The mutated gene was identified by map-based cloning as NCA1, which encodes a protein containing an N-terminal RING-finger domain and a C-terminal tetratricopeptide repeat-like helical domain. NCA1 interacts with and increases catalase activity maximally in a 240-kD complex in planta. In vitro, NCA1 interacts with CATALASE2 (CAT2) in a 1:1 molar ratio, and the NCA1 C terminus is essential for this interaction. CAT2 activity increased 10-fold in the presence of NCA1, and zinc ion binding of the NCA1 N terminus is required for this increase. NCA1 has chaperone protein activity that may maintain the folding of catalase in a functional state. NCA1 is a cytosol-located protein. Expression of <I>NCA1</I> in the mitochondrion of the <I>nca1-3</I> mutant does not rescue the abiotic stress phenotypes of the mutant, while expression in the cytosol or peroxisome does. Our results suggest that NCA1 is essential for catalase activity.</P>