Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe

Runsha Xiao,Fan Zheng,Kuo Kang,Lei Xiao,Anyao Bi,Yiting Chen,Qi Zhou,Xueping Feng,Zhikang Chen,Hao Yin,Wei Wang,Zihua Chen,Xiaomiao Cheng,Wenbin Zeng 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. Methods Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. Results We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. Conclusions In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI’s properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

Chemical–Mechanical Polishing of Cemented Carbide Insert Surface for Extended Tool Life in Turning of GH4169 Nickel-Based Superalloy

Zihua Hu,Changjiang Qin,Xiaogao Chen,Aimin Tang,Tao Fang,Zhiping Yang,Sheng Luo,Meijiao Mao 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.8

To extend the tool life of conventional uncoated grinding cemented carbide inserts (CUG inserts) in turning GH4169 nickelbased superalloy, chemical–mechanical polishing (CMP) is applied to appropriately treat the rake face of the CUG insert to address the defects including grinding burn, crack, and thermal deformation. The material removal rate (MRR) and the rake face roughness Ra of YG10 chemical–mechanical polished cemented carbide inserts (CMP inserts) corresponding to the six types of abrasives particles are investigated by applying the single factor method, and the diamond powder is the most suitable to polish YG10 inserts. Thus, CMP parameters are optimized using Taguchi method coupled with both the grey relation analysis and fuzzy inference. Furthermore, the comparison experiments of the cutting performance of the CUG insert and the CMP insert in turning GH4169 are carried out, under the same cutting condition, compared with the CUG insert, the average tool life of the CMP insert is increased by 35.92%. This study demonstrates that the CMP technique is an effective potential method to improve the surface integrity, the cutting performance and the tool life of conventional uncoated grinding cemented carbide inserts & tools in the machining of difficult-to-cut materials.

Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage.

Gong, Zihua,Cho, Young-Wook,Kim, Ja-Eun,Ge, Kai,Chen, Junjie American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.11

<P>Genomic stability in eukaryotic cells is maintained by the coordination of multiple cellular events including cell cycle checkpoint, DNA repair, transcription, and apoptosis after DNA damage. Pax2 transactivation domain interaction protein (PTIP), a protein that contains six BRCT domains, has been implicated in DNA damage response. In this study we showed that recruitment of PTIP to damaged chromatin depends on DNA damage signaling proteins gammaH2AX.MDC1.RNF8, which in turn facilitates sustained localization of PA1 (PTIP-associated protein 1) to sites of DNA break. Similar to PTIP, depletion of PA1 increases cellular sensitivity to ionizing radiation. Furthermore, we demonstrated that the N-terminal PA1 binding domain and the C-terminal focus-localization domain of PTIP are critical for PTIP function in DNA damage repair. Interestingly, although PTIP and PA1 associate with MLL (mixed lineage leukemia) complexes and participate in transcriptional regulation, this function of PTIP.PA1 in DNA damage response is likely to be independent of the MLL complexes. Taken together, we propose that a subset of PTIP.PA1 complex is recruited to DNA damage sites via the RNF8-dependent pathway and is required for cell survival in response to DNA damage.</P>

BACH1/FANCJ Acts with TopBP1 and Participates Early in DNA Replication Checkpoint Control

Gong, Zihua,Kim, Ja-Eun,Leung, Charles Chung Yun,Glover, J.N. Mark,Chen, Junjie Elsevier 2010 Molecular cell Vol.37 No.3

<P><B>Summary</B></P><P>Human TopBP1 plays a critical role in the control of DNA replication checkpoint. In this study, we report a specific interaction between TopBP1 and BACH1/FANCJ, a DNA helicase involved in the repair of DNA crosslinks. The TopBP1/BACH1 interaction is mediated by the very C-terminal tandem BRCT domains of TopBP1 and S phase-specific phosphorylation of BACH1 at Thr 1133 site. Interestingly, we demonstrate that depletion of TopBP1 or BACH1 attenuates the loading of RPA on chromatin. Moreover, both TopBP1 and BACH1 are required for ATR-dependent phosphorylation events in response to replication stress. Taken together, our data suggest that BACH1 has an unexpected early role in replication checkpoint control. A specific interaction between TopBP1 and BACH1 is likely to be required for the extension of single-stranded DNA regions and RPA loading following replication stress, which is a prerequisite for the subsequent activation of replication checkpoint.</P> <P><B>Highlights</B></P><P>► Human TopBP1 interacts with BACH1 in a phosphorylation-dependent manner ► TopBP1 or BACH1 depletion attenuates RPA chromatin loading after replication stress ► Both TopBP1 and BACH1 are required for ATR-dependent replication checkpoint activation</P>

Morphology Controlled Synthesis of Octahedral Covalent Imine Frameworks Through Acid Modulated Aldehyde-Amine Polycondensation

Lili Pan,Zihua Chen,Wenxiu De,Guangjie Yang,Xikui Liu 한국고분자학회 2016 Macromolecular Research Vol.24 No.4

The past decades have witnessed significant advance in the synthesis of covalent organic frameworks (COFs), however, their formation and morphology revolution mechanism have been rarely reported. Here, through an acid modulated dynamic covalent chemistry approach, pure and uniform micro-octahedral covalent imine frameworks were obtained for the first time. Formation mechanism based on the stacking of initially formed two-dimensional nanoplates followed by surface smoothing enabled by the dynamic nature of imine bonding was proposed. Furthermore, we revealed for the first time that nonstoichiometric method can be applied to the synthesis of covalent organic frameworks. Thus we provide novel strategy for the morphology control COFs which will surely facilitate their application in energy-related area.

Characterization of the DOT1L Network: Implications of Diverse Roles for DOT1L

Park, Geunyeong,Gong, Zihua,Chen, Junjie,Kim, Ja-Eun Springer-Verlag 2010 The Protein Journal Vol.29 No.3