Publications by authors named "Kaitao Li"

37 Publications

Association of Fibrosis in Bulge Portion with Hair Follicle Miniaturization in Androgenetic Alopecia.

J Am Acad Dermatol 2021 Feb 1. Epub 2021 Feb 1.

Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, 1838 North Guangzhou AV, Guangzhou, Guangdong Province, 510515, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.01.078DOI Listing
February 2021

Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia.

Biomed Pharmacother 2021 Jan 29;137:111247. Epub 2021 Jan 29.

Department of Plastic and Aesthetic Surgery Nanfang Hospital of Southern Medical University Guangzhou, Guangdong Province, 510515, China. Electronic address:

Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.
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http://dx.doi.org/10.1016/j.biopha.2021.111247DOI Listing
January 2021

Impairment of autophagy may be associated with follicular miniaturization in androgenetic alopecia by inducing premature catagen.

J Dermatol 2021 Mar 1;48(3):289-300. Epub 2020 Dec 1.

Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China.

Androgenetic alopecia is the most common form of hair loss disorder. The features of this process are shortening of the anagen phase in hair cycling and progressive miniaturization of the hair follicle. However, the mechanisms in androgenetic alopecia are still unclear, and the treatment methods are also limited. Therefore, further study on the pathogenesis and new therapies for androgenetic alopecia are urgently needed. In this study, we found that endogenous autophagy was severely impaired, accompanied by increased apoptosis in early catagen-like miniaturized hair follicles from the balding scalps of androgenetic alopecia patients. Moreover, inhibition of autophagy using 3-methyladenine could induce apoptosis, premature hair follicle regression and slow down the hair growth in organ-cultured hair follicles. Taken together, these results suggest that impairment of autophagy could be a potential mechanism in androgenetic alopecia.
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http://dx.doi.org/10.1111/1346-8138.15672DOI Listing
March 2021

Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation.

Cell Rep 2020 Oct;33(4):108327

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China. Electronic address:

Abnormal activation of calcium channels has been shown to play crucial roles in tumor occurrence and development. However, the role of inhibitors targeting calcium channels in tumor progression and immune regulation remains unclear, and their clinical applications are still limited. We show that nifedipine (NIFE), a calcium channel blocker, inhibits calcium influx to impair nuclear factor of activated T cell 2 (NFAT2) dephosphorylation, activation, and nuclear translocation, thus preventing transcriptional activation of downstream signaling molecules to suppress colorectal cancer (CRC) proliferation and metastasis. In addition, NIFE decreases expression of programmed death-ligand 1 (PD-L1) on CRC cells and programmed death-1 (PD-1) on CD8 T cells and reactivates tumor immune monitoring, which may stimulate or enhance PD-1-based antitumor immunotherapy. Our findings provide direct evidence that NIFE is a promising clinical therapy to treat patients with advanced CRC by affecting the tumor itself and tumor immunity. NIFE may be a promising therapeutic option to enhance effectiveness of immune checkpoint blockade therapy in CRC.
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http://dx.doi.org/10.1016/j.celrep.2020.108327DOI Listing
October 2020

Novel Fluorescence Method for Determination of Spatial Interparticle Distance in Polymer Nanocomposites.

Anal Chem 2020 06 19;92(11):7794-7799. Epub 2020 May 19.

Kemai Chemical Co., Ltd., Tianjin 300270, China.

Interparticle distance (ID) is generally used for spatial evaluation on the dispersion of nanofillers in polymer nanocomposites (PNCs) in order to gain in-depth insight into fundamental understanding of reinforcement and structure-property correlation. However, currently available methods mainly rely on two-dimensional observation technologies or simulation methods. Herein, using layered double hydroxides (LDHs) in low-density polyethylene (LDPE) as a model matrix, we developed a novel spatial ID determination method through a post labeling fluorescent imaging technique. The spatial ID of LDH nanofillers was achieved by a MATLAB program based on the 3D coordinates of LDH nanofillers in PNCs. The spatial ID data indicated the varied dispersion states of LDH nanofillers from "random", "even", to "clustered" in PNCs. More importantly, the so-called exceptional performances of PNCs at high loading of LDH nanofillers can be reasonably explained in combination with the mechanical studies. This proposed approach could undoubtedly provide valuable information in elucidating the structure-property correlation in PNCs. We believe that this work would be a guide to design advanced PNC materials.
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http://dx.doi.org/10.1021/acs.analchem.0c00957DOI Listing
June 2020

Single-molecule investigations of T-cell activation.

Curr Opin Biomed Eng 2019 Dec 1;12:102-110. Epub 2019 Nov 1.

Wallace H. Coulter Department of Biomedical Engineering.

T-cell activation is the central event governing its development, differentiation, and effector functions. T-cell activation is initiated by the direct physical interaction of the T cell antigen receptor (TCR) with cognate peptide presented by the major histocompatibility complex (pMHC) molecule expressed on the antigen presenting cell (APC) surface. Since the identification of TCR as the only receptor for antigen on T cells three decades ago, studies have elucidated the major molecular players and signaling events responding to TCR stimulation. However, the question of how the physical event of pMHC binding is converted across the membrane into chemical events to initiate signal transduction remains elusive. Here we review recent investigations of T-cell activation using single-molecule force and fluorescence techniques that shed new light on this key question.
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http://dx.doi.org/10.1016/j.cobme.2019.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158867PMC
December 2019

Mechanotransduction in T Cell Development, Differentiation and Function.

Cells 2020 02 5;9(2). Epub 2020 Feb 5.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Cells in the body are actively engaging with their environments that include both biochemical and biophysical aspects. The process by which cells convert mechanical stimuli from their environment to intracellular biochemical signals is known as mechanotransduction. Exemplifying the reliance on mechanotransduction for their development, differentiation and function are T cells, which are central to adaptive immune responses. T cell mechanoimmunology is an emerging field that studies how T cells sense, respond and adapt to the mechanical cues that they encounter throughout their life cycle. Here we review different stages of the T cell's life cycle where existing studies have shown important effects of mechanical force or matrix stiffness on a T cell as sensed through its surface molecules, including modulating receptor-ligand interactions, inducing protein conformational changes, triggering signal transduction, amplifying antigen discrimination and ensuring directed targeted cell killing. We suggest that including mechanical considerations in the immunological studies of T cells would inform a more holistic understanding of their development, differentiation and function.
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http://dx.doi.org/10.3390/cells9020364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072571PMC
February 2020

Author Correction: Mechanosensing through immunoreceptors.

Nat Immunol 2019 Dec;20(12):1700

Wallace H. Coulter Department of Biomedical Engineering, Atlanta, GA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41590-019-0545-4DOI Listing
December 2019

Mechanosensing through immunoreceptors.

Nat Immunol 2019 10 18;20(10):1269-1278. Epub 2019 Sep 18.

Wallace H. Coulter Department of Biomedical Engineering, Atlanta, GA, USA.

The immune response is orchestrated by a variety of immune cells. The function of each cell is determined by the collective signals from various immunoreceptors, whose expression and activity depend on the developmental stages of the cell and its environmental context. Recent studies have highlighted the presence of mechanical force on several immunoreceptor-ligand pairs and the important role of force in regulating their interaction and function. In this Perspective, we use the T cell antigen receptor as an example with which to review the current understanding of the mechanosensing properties of immunoreceptors. We discuss the types of forces that immunoreceptors may encounter and the effects of force on ligand bonding, conformational change and the triggering of immunoreceptors, as well as the effects of force on the downstream signal transduction, cell-fate decisions and effector function of immune cells.
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http://dx.doi.org/10.1038/s41590-019-0491-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592628PMC
October 2019

Biophysical basis underlying dynamic Lck activation visualized by ZapLck FRET biosensor.

Sci Adv 2019 06 19;5(6):eaau2001. Epub 2019 Jun 19.

Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.

Lck plays crucial roles in TCR signaling. We developed a new and sensitive FRET biosensor (ZapLck) to visualize Lck kinase activity with high spatiotemporal resolutions in live cells. ZapLck revealed that 62% of Lck signal was preactivated in T-cells. In Lck-deficient JCam T-cells, Lck preactivation was abolished, which can be restored to 51% by reconstitution with wild-type Lck (LckWT) but not a putatively inactive mutant LckY394F. LckWT also showed a stronger basal Lck-Lck interaction and a slower diffusion rate than LckY394F. Interestingly, aggregation of TCR receptors by antibodies in JCam cells led to a strong activation of reconstituted LckY394F similar to LckWT. Both activated LckY394F and LckWT diffused more slowly and displayed increased Lck-Lck interaction at a similar level. Therefore, these results suggest that a phosphorylatable Y394 is necessary for the basal-level interaction and preactivation of LckWT, while antibody-induced TCR aggregation can trigger the full activation of LckY394F.
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http://dx.doi.org/10.1126/sciadv.aau2001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584686PMC
June 2019

Observational study of aerosol-induced impact on planetary boundary layer based on lidar and sunphotometer in Beijing.

Environ Pollut 2019 Sep 18;252(Pt A):897-906. Epub 2019 May 18.

State Environment Protection Key Laboratory of Satellite Remote Sensing, Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100101, China.

Atmospheric aerosols have been found to influence the development of planetary boundary layer (PBL) and hence to aggravate haze pollution in megacities. PBL height (PBLH) determines the vertical extent to which the most pollutant effectively disperses and is a key argument in pollution study. In this study, we quantitatively evaluate aerosol radiation effect on PBL, as well as assessment of surface cooling effect and atmosphere heating effect. All the data are measured at a site of Beijing from 2014 to 2017, of which PBLH is retrieved from micro pulse lidar and aerosol optical depth (AOD) from sunphotometer. Case study shows qualitatively that relative high aerosol load reduces PBLH, and in turn causes a high surface PM concentration. We preliminarily reveal the influential mechanism of aerosol on PBL. The influence of aerosol on the radiation flux of PBL is analyzed, with the correlation coefficient (R) of 0.938 between AOD and radiative forcing of BOA (RF) and R = 0.43 between RF and PBLH. Also, AOD is found to negatively correlate with PBLH (R = -0.41). With the increase of AOD, the cooling effect of surface is enhanced, and further impede the development of PBL. Due to aerosol-induced reduction of PBLH, near surface PM concentration surges and presents an exponential growth following AOD. Then, it is speculated and testified that the relationship between SSA (single scatting albedo) and PBLH would be determined by the location of absorbing aerosol within PBL. The upper PBL absorbing aerosol may decrease PBLH, while the lower absorbing aerosol appear to enhance PBLH. The study probably can provide effective observational evidence for understanding the effect of aerosol on PBL and be a reference of air pollution mitigation in Beijing and its surrounding areas.
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http://dx.doi.org/10.1016/j.envpol.2019.05.070DOI Listing
September 2019

A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer.

EBioMedicine 2019 Jun 9;44:311-321. Epub 2019 May 9.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address:

Background: Gastric cancer (GC) ranks the fifth most common cancer, and chemotherapy is one of the most common treatments for GC. However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. This study aims to investigate the biological effect of miR-567 on gastric tumourigenesis and chemoresistance and reveal the possible mechanism.

Methods: We measured the expression of miR-567 in 37 paired normal and stomach tumour specimens, as well as GC cell lines by Real-time PCR. The functional effects of miR-567 were validated using in vitro and in vivo assays. Dual-luciferase report assays and Chromatin immunoprecipitation (ChIP) assay were conducted for target evaluation, western blot assay was used to confirm the relationships.

Findings: Our data showed that miR-567 was downregulated in gastric tissues and gastric cancer cells compared with normal tissues and gastric epithelial cells. In vitro, Gain- and lose-of-function assays showed miR-567 not only weakened cells proliferative ability, but also sensitized GC cells to 5-FU and oxaliplatin. In vivo, miR-567 overexpression significantly repressed the tumourigenesis of GC cells compared with the vector control. Mechanistic analysis showed that PIK3AP1 activated AKT phosphorylation in GC. Meanwhile, miR-567 directly targeted PIK3AP1 to inactivate PI3K/AKT/c-Myc pathway and c-Myc inversely regulated miR-567 expression, thus forming a miR-567-PIK3AP1- PI3K/AKT-c-Myc feedback loop explaining the function of miR-567.

Interpretation: Our studies revealed that miR-567 acts as a tumour suppressor gene and suppresses GC tumorigenesis and chemoresistance via a miR-567-PIK3AP1- PI3K/AKT-c-Myc feedback loop. These results suggest that miR-567 may serve as a target for chemoresistance and a potential prognostic biomarker for GC.
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http://dx.doi.org/10.1016/j.ebiom.2019.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603849PMC
June 2019

Substrate-Assisted Visualization of Surfactant Micelles via Transmission Electron Microscopy.

Front Chem 2019 11;7:242. Epub 2019 Apr 11.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China.

The visualization of the micellar morphological evolution for surfactant has drawn much attention due to its self-assemble ability to fold into various structures. However, the direct observation of the soft materials with low atomic number has been hampered because of the poor scattering contrast and complex staining process by the traditional transmission electron microscopy (TEM) techniques. Herein, we reported a novel strategy to the visualization of surfactant micelles with the assistance of layered double hydroxides (LDHs) via TEM. Owing to the uniformly distributed metal ions and positive charges in the LDHs, the surfactant at the micelle-water interface reacted with LDHs to form a stabilized architecture through electrostatic and hydrogen-bond interactions. The morphologies of the surfactant can be clearly observed through the surfactant-LDHs architectures, exhibiting high contrast by TEM techniques. Significantly, the micellar evolutions involving the spherical, rodlike, and wormlike shapes were successfully distinguished. Our results may provide great possibilities and inspirations for the visualization for morphology of soft matters.
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http://dx.doi.org/10.3389/fchem.2019.00242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470246PMC
April 2019

In situ visualization of hydrophilic spatial heterogeneity inside microfluidic chips by fluorescence microscopy.

Lab Chip 2019 03;19(6):934-940

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Fluorescence visualization for hydrophilic spatial heterogeneity inside microfluidic chips is a long-standing challenge owing to the lack of fluorescent dyes with high contrast between the target and the background noise. Herein, we used boronic acid in aggregation-induced emission (AIE) molecules as an anchor group towards modified hydroxyl groups, and an in situ visualization approach for hydrophilic spatial heterogeneity inside microfluidic chips was demonstrated. This success is based on the high-contrast of fluorescent behaviors for AIE molecules in aqueous solution and their immobilization by hydroxyl groups inside the microfluidic channels. In comparison to conventional laboratory-based ex situ techniques, the proposed strategy provides a direct representation for hydrophilic spatial heterogeneity, including the quantity and distribution of hydroxyl groups. This discovery not only identifies a previously unknown variability in hydrophilic spatial heterogeneity inside microfluidic channels, but also guides an optimal hydrophilic modification method in the channels.
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http://dx.doi.org/10.1039/c8lc01336eDOI Listing
March 2019

Aggregation-Induced Emission for Visualization in Materials Science.

Chem Asian J 2019 Mar 25;14(6):715-729. Epub 2019 Jan 25.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, P.O. Box 79, 100029, Beijing, China.

Fluorescent imaging techniques have attracted much attention as a powerful tool to realize the visualization of structural and morphological evolution of various materials. However, the traditional fluorescent dyes usually suffered from aggregation-caused quenching, which severely limits the visualization results. In contrast, aggregation-induced emission (AIE) molecules with high quantum yields in the condensed state showed great opportunities for imaging techniques. In this feature article, recent progresses in visualization with AIE molecules are discussed. Assembly processes including crystallization, gelation process, and dissipative assembly have been observed. To better study information obtained regarding the processes, visualization during reactions, phase transitions, and molecular motions are successfully presented. Based on these successes, AIE molecules were further applied for phase recognition, macro-dispersion evaluation, and damage detection. Finally, we also present the outlook and perspectives, in our opinion, for the development of visualization by AIE molecules.
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http://dx.doi.org/10.1002/asia.201801760DOI Listing
March 2019

The relationship between self-esteem and hair transplantation satisfaction in male androgenetic alopecia patients.

J Cosmet Dermatol 2018 Dec 23. Epub 2018 Dec 23.

Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China.

Background: Frustrated with the embarrassing appearance, patients with androgenetic alopecia (AGA) suffer from poor quality of life and low self-esteem. Moreover, several researches indicate that self-esteem is an important factor affecting outcomes of cosmetic surgery.

Objective: This retrospective study aims to investigate the impact of hair transplantation on patients' self-esteem and satisfaction with appearance, as well as relationship between self-esteem and patient satisfaction which includes preoperative and postoperative satisfaction.

Methods: The preoperative and 9-month postoperative self-esteem were evaluated by Rosenberg Self-Esteem Scale (RSES), and preoperative satisfaction indicators (satisfaction with appearance, visual age and expected visual age) were assessed by Face-Q scale. At the same time, postoperative satisfaction indicators (satisfaction with appearance, visual age, satisfaction with decision, psychological well-being, and social function) were reevaluated as well.

Results: Of the 1106 male AGA patients, 875 completed a 9-month postoperative questionnaire. Compared with preoperative scores, postoperative scores of self-esteem and satisfaction with appearance showed an increase of 1.56 and 30.25 respectively (P < 0.05). Subgroup analysis showed that patients with high self-esteem level trended to have higher scores of postoperative satisfaction with appearance (P = 0.129), psychological well-being (P = 0.168), social function (P = 0.027), and satisfaction with decision (P = 0.043) compared with patients with low and average self-esteem level.

Conclusion: Hair transplantation significantly elevated self-esteem level and increased satisfaction with appearance of AGA patients. Meanwhile, patients with low self-esteem level trended to have worse postoperative satisfaction. Thus, apart from ensuring the quality of operation, plastic surgeons should offer guidance based on patients' psychological state to improve postoperative satisfaction.
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http://dx.doi.org/10.1111/jocd.12839DOI Listing
December 2018

Highly dispersed layered double oxide hollow spheres with sufficient active sites for adsorption of methyl blue.

Nanoscale 2018 Dec 5;10(48):23191-23197. Epub 2018 Dec 5.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

The adsorption of dyes in contaminated water is an effective approach to solving the environmental crisis. Layered double hydroxide (LDH) and its calcinated product layered double oxide (LDO) show great potential as adsorbents. However, the conventional preparation of LDH or LDO typically suffers from aggregation and blocked active sites, hampering the adsorption efficiency of the adsorbent. Herein, three-dimensional, hollow MgFe-LDO spheres were constructed through the sacrifice of a carbon template. The hollow structure and the monodisperse state provided MgFe-LDO with sufficient microchannels and abundant active sites for adsorption. Through the memory effect of LDO, the anion methyl blue (MB) can be effectively adsorbed with a high uptake capacity of 398 mg g. Isotherm simulations demonstrated the monolayer adsorption of MB and the heterogeneous surfaces of the reconstructed LDHs. Moreover, the adsorbents can be recycled and reutilized at least five times through magnetic separation followed by calcination. Our proposed strategy is expected to provide new possibilities for the construction of adsorbents with well-controlled architecture and abundant active sites to deal with anionic pollutants.
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http://dx.doi.org/10.1039/c8nr08117dDOI Listing
December 2018

A TCR mechanotransduction signaling loop induces negative selection in the thymus.

Nat Immunol 2018 12 12;19(12):1379-1390. Epub 2018 Nov 12.

Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR-pMHC-CD8 trimolecular 'catch bonds', whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR-pMHC and pMHC-CD8 bimolecular 'slip bonds'. Catch bonds were not intrinsic to either the TCR-pMHC or the pMHC-CD8 arm of the trans (cross-junctional) heterodimer but resulted from coupling of the extracellular pMHC-CD8 interaction to the intracellular interaction of CD8 with TCR-CD3 via associated kinases to form a cis (lateral) heterodimer capable of inside-out signaling. We suggest that the coupled trans-cis heterodimeric interactions form a mechanotransduction loop that reinforces negative-selection signaling that is distinct from positive-selection signaling in the thymus.
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http://dx.doi.org/10.1038/s41590-018-0259-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452639PMC
December 2018

miR-589 promotes gastric cancer aggressiveness by a LIFR-PI3K/AKT-c-Jun regulatory feedback loop.

J Exp Clin Cancer Res 2018 Jul 16;37(1):152. Epub 2018 Jul 16.

Department of Medical Oncology, Affiliated Cancer Hospital & Institutes of Guangzhou Medical University, Guangzhou, China.

Background: As novel biomarkers for various cancers, microRNAs negatively regulate genes expression via promoting mRNA degradation and suppressing mRNA translation. miR-589 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in gastric cancer. Here, we aim to investigate the biological effect of miR-589 on gastric cancer and to reveal the possible mechanism.

Methods: Real-time PCR was performed to evaluate the expression of miR-589 in 34 paired normal and stomach tumor specimens, as well as gastric cell lines. Functional assays, such as wound healing, transwell assays and in vivo assays, were used to detect the biological effect of miR-589 and LIFR. We determined the role of miR-589 in gastric cancer tumorigenesis in vivo using xenograft nude models. Dual-luciferase report assays and Chromatin immunoprecipitation (ChIP) assay were performed for target evaluation, and the relationships were confirmed by western blot assay.

Result: MiR-589 expression was significantly higher in tumor tissues and gastric cancer cells than those in matched normal tissues and gastric epithelial cells, respectively. Clinically, overexpression of miR-589 is associated with tumor metastasis, invasion and poor prognosis of GC patients. Gain- and loss-of function experiments showed that miR-589 promoted cell migration, metastasis and invasion in vitro and lung metastasis in vivo. Mechanistically, we found that miR-589 directly targeted LIFR to activate PI3K/AKT/c-Jun signaling. Meanwhile, c-Jun bound to the promoter region of miR-589 and activated its transcription. Thus miR-589 regulated its expression in a feedback loop that promoted cell migration, metastasis and invasion.

Conclusion: Our study identified miR-589, as an oncogene, markedly induced cell metastasis and invasion via an atypical miR-589-LIFR-PI3K/AKT-c-Jun feedback loop, which suggested miR-589 as a potential biomarker and/or therapeutic target for the gastric cancer management.
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http://dx.doi.org/10.1186/s13046-018-0821-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048856PMC
July 2018

Aerosol optical, microphysical, chemical and radiative properties of high aerosol load cases over the Arctic based on AERONET measurements.

Sci Rep 2018 Jun 20;8(1):9376. Epub 2018 Jun 20.

Environment Protection Key Laboratory of Satellite Remote Sensing, Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, Beijing, 100101, China.

Columnar mass concentrations of aerosol components over the Arctic are estimated using microphysical parameters derived from direct sun extinction and sky radiance measurements of Aerosol Robotic Network. Aerosol optical, microphysical, chemical and radiative properties show that Arctic aerosols are dominated by fine mode particles, especially for high aerosol load cases. The average aerosol optical depth (AOD) of the selected Arctic sites in the sampling period is approximately 0.08, with 75% composed of fine mode particles. The fine mode fraction mostly exceeds 0.9 when AOD greater than 0.4. The ammonium sulfate-like component (AS) contributes about 68% of total dry aerosol mass for high-AOD events. The estimated compositions and back trajectories show that the transported aerosol particles from biomass burning events have large amounts of black carbon (BC) and brown carbon, while those from pollution events are characterised by large AS fractions. The instantaneous radiative forcing at the top-of-atmosphere is higher for the more absorbing components, and varies greatly with surface albedo and solar zenith angle. A regression model of columnar composition and radiative forcing within the atmosphere (RF) for Arctic aerosol is established, showing that BC dominates a positive RF with a high warming efficiency.
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http://dx.doi.org/10.1038/s41598-018-27744-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010420PMC
June 2018

LASP1 promotes nasopharyngeal carcinoma progression through negatively regulation of the tumor suppressor PTEN.

Cell Death Dis 2018 03 12;9(3):393. Epub 2018 Mar 12.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells. LASP1 interacted with PTEN and decreased the expression of PTEN in NPC. The ubiquitination assay indicated that LASP1 overexpression increased PTEN ubiquitination. PTEN was known as a tumor suppressor by negatively regulating phosphoinositide 3-kinase/AKT signaling pathway. Rescue experiments showed that PTEN weakened LASP1-mediated cell proliferation, migration, and invasive abilities and decreased the phosphorylation of AKT in NPC cells. Our findings suggest that LASP1 has a crucial role in NPC progression via LASP1/PTEN/AKT axis, highlighting LASP1 as a therapeutic target for NPC.
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http://dx.doi.org/10.1038/s41419-018-0443-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847534PMC
March 2018

Calibration of the degree of linear polarization measurements of the polarized Sun-sky radiometer based on the POLBOX system.

Appl Opt 2018 Feb;57(5):1011-1018

Polarization observation of sky radiation is the frontier approach to improve the remote sensing of atmospheric components, e.g., aerosol and clouds. The polarization calibration of the ground-based Sun-sky radiometer is the basis for obtaining accurate degree of linear polarization (DOLP) measurement. In this paper, a DOLP calibration method based on a laboratory polarized light source (POLBOX) is introduced in detail. Combined with the CE318-DP Sun-sky polarized radiometer, a calibration scheme for DOLP measurement is established for the spectral range of 440-1640 nm. Based on the calibration results of the Sun-sky radiometer observation network, the polarization calibration coefficient and the DOLP calibration residual are analyzed statistically. The results show that the DOLP residual of the calibration scheme is about 0.0012, and thus it can be estimated that the final DOLP calibration accuracy of this method is about 0.005. Finally, it is verified that the accuracy of the calibration results is in accordance with the expected results by comparing the simulated DOLP with the vector radiative transfer calculations.
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http://dx.doi.org/10.1364/AO.57.001011DOI Listing
February 2018

Dual Biomembrane Force Probe enables single-cell mechanical analysis of signal crosstalk between multiple molecular species.

Sci Rep 2017 10 27;7(1):14185. Epub 2017 Oct 27.

Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, 30332, GA, United States.

Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP). The dBFP provides precise controls and quantitative readouts in both mechanical and chemical terms, which is particularly suited for juxtacrine signaling and mechanosensing studies. Specifically, the dBFP allows us to analyze dual receptor crosstalk by quantifying the spatiotemporal requirements and functional consequences of the up- and down-stream signaling events. In this work, the utility and power of the dBFP has been demonstrated in four important dual receptor systems that play key roles in immunological synapse formation, shear-dependent thrombus formation, and agonist-driven blood clotting.
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http://dx.doi.org/10.1038/s41598-017-13793-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660210PMC
October 2017

Absence of physiological Ca transients is an initial trigger for mitochondrial dysfunction in skeletal muscle following denervation.

Skelet Muscle 2017 04 10;7(1). Epub 2017 Apr 10.

Rush University School of Medicine, Chicago, IL, USA.

Background: Motor neurons control muscle contraction by initiating action potentials in muscle. Denervation of muscle from motor neurons leads to muscle atrophy, which is linked to mitochondrial dysfunction. It is known that denervation promotes mitochondrial reactive oxygen species (ROS) production in muscle, whereas the initial cause of mitochondrial ROS production in denervated muscle remains elusive. Since denervation isolates muscle from motor neurons and deprives it from any electric stimulation, no action potentials are initiated, and therefore, no physiological Ca transients are generated inside denervated muscle fibers. We tested whether loss of physiological Ca transients is an initial cause leading to mitochondrial dysfunction in denervated skeletal muscle.

Methods: A transgenic mouse model expressing a mitochondrial targeted biosensor (mt-cpYFP) allowed a real-time measurement of the ROS-related mitochondrial metabolic function following denervation, termed "mitoflash." Using live cell imaging, electrophysiological, pharmacological, and biochemical studies, we examined a potential molecular mechanism that initiates ROS-related mitochondrial dysfunction following denervation.

Results: We found that muscle fibers showed a fourfold increase in mitoflash activity 24 h after denervation. The denervation-induced mitoflash activity was likely associated with an increased activity of mitochondrial permeability transition pore (mPTP), as the mitoflash activity was attenuated by application of cyclosporine A. Electrical stimulation rapidly reduced mitoflash activity in both sham and denervated muscle fibers. We further demonstrated that the Ca level inside mitochondria follows the time course of the cytosolic Ca transient and that inhibition of mitochondrial Ca uptake by Ru360 blocks the effect of electric stimulation on mitoflash activity.

Conclusions: The loss of cytosolic Ca transients due to denervation results in the downstream absence of mitochondrial Ca uptake. Our studies suggest that this could be an initial trigger for enhanced mPTP-related mitochondrial ROS generation in skeletal muscle.
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http://dx.doi.org/10.1186/s13395-017-0123-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387329PMC
April 2017

and kinetic analyses of programmed cell death-1 (PD-1) receptor, programmed cell death ligands, and B7-1 protein interaction network.

J Biol Chem 2017 04 6;292(16):6799-6809. Epub 2017 Mar 6.

the Coulter Department of Biomedical Engineering, the Woodruff School of Mechanical Engineering, and the Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta 30332-0535, Georgia

Programmed cell death-1 (PD-1) is an inhibitory receptor with an essential role in maintaining peripheral tolerance and is among the most promising immunotherapeutic targets for treating cancer, autoimmunity, and infectious diseases. A complete understanding of the consequences of PD-1 engagement by its ligands, PD-L1 and PD-L2, and of PD-L1 binding to B7-1 requires quantitative analysis of their interactions at the cell surface. We present here the first complete kinetic analysis of the PD-1/PD-ligands/B7-1 system. Consistent with previous solution measurements, we observed higher affinities for human (h) than murine (m) PD-1 interactions, stronger binding of hPD-1 to hPD-L2 than hPD-L1, and comparable binding of mPD-1 to both ligands. However, in contrast to the relatively weak solution affinities, the affinities of PD-1 are as high as those of the T cell receptor for agonist pMHC and of LFA-1 (lymphocyte function-associated antigen 1) for ICAM-1 (intercellular adhesion molecule 1) but significantly lower than that of the B7-1/CTLA-4 interaction, suggesting a distinct basis for PD-1- CTLA-4-mediated inhibition. Notably, the interactions of PD-1 are much stronger than that of B7-1 with PD-L1. Overall, the affinity ranking greatly depends on the on-rate instead of the off-rate. simulations predict that PD-1/PD-L1 interactions dominate at interfaces between activated T cells and mature dendritic cells and that these interactions will be highly sensitive to the dynamics of PD-L1 and PD-L2 expression. Our results provide a kinetic framework for better understanding inhibitory PD-1 activity in health and disease.
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http://dx.doi.org/10.1074/jbc.M116.763888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399126PMC
April 2017

Simple transfer calibration method for a Cimel Sun-Moon photometer: calculating lunar calibration coefficients from Sun calibration constants.

Appl Opt 2016 Sep;55(27):7624-30

The Cimel new technologies allow both daytime and nighttime aerosol optical depth (AOD) measurements. Although the daytime AOD calibration protocols are well established, accurate and simple nighttime calibration is still a challenging task. Standard lunar-Langley and intercomparison calibration methods both require specific conditions in terms of atmospheric stability and site condition. Additionally, the lunar irradiance model also has some known limits on its uncertainty. This paper presents a simple calibration method that transfers the direct-Sun calibration constant, V0,Sun, to the lunar irradiance calibration coefficient, CMoon. Our approach is a pure calculation method, independent of site limits, e.g., Moon phase. The method is also not affected by the lunar irradiance model limitations, which is the largest error source of traditional calibration methods. Besides, this new transfer calibration approach is easy to use in the field since CMoon can be obtained directly once V0,Sun is known. Error analysis suggests that the average uncertainty of CMoon over the 440-1640 nm bands obtained with the transfer method is 2.4%-2.8%, depending on the V0,Sun approach (Langley or intercomparison), which is comparable with that of lunar-Langley approach, theoretically. In this paper, the Sun-Moon transfer and the Langley methods are compared based on site measurements in Beijing, and the day-night measurement continuity and performance are analyzed.
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http://dx.doi.org/10.1364/AO.55.007624DOI Listing
September 2016

Imaging Spatiotemporal Activities of ZAP-70 in Live T Cells Using a FRET-Based Biosensor.

Ann Biomed Eng 2016 12 6;44(12):3510-3521. Epub 2016 Jul 6.

Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

The zeta-chain-associated protein kinase 70 kDa (ZAP-70), a member of the spleen tyrosine kinase (Syk) family, plays an essential role in early T cell receptor (TCR) signaling. Defects in ZAP-70 lead to impaired thymocyte development and peripheral T cell activation. To better understand its activation dynamics and regulation, we visualized ZAP-70 activities in single live T cells with a Förster resonance energy transfer (FRET)-based biosensor, which was designed for probing kinase activities of the Syk family. We observed in Jurkat E6.1 T cells rapid and specific FRET changes following anti-CD3 stimulation and subsequent piceatannol inhibition. The initiation of ZAP-70 activation was prompt (within 10 s) and correlates with the accompanied intracellular calcium elevation, as revealed by simultaneous imaging of the biosensor and calcium. Different from the previously reported ZAP-70 activation in the immunological synapse and the opposite pole (anti-synapse), we have observed rapid and sustained ZAP-70 activation only at the synapse with superantigen-pulsed Raji B cells. Furthermore, ZAP-70 signaling was impaired by cholesterol depletion, further supporting the importance of membrane organization in TCR signaling. Together our results provide a direct characterization of the spatiotemporal features of ZAP-70 activity in real time at subcellular levels.
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http://dx.doi.org/10.1007/s10439-016-1683-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114152PMC
December 2016

Method to intercalibrate sunphotometer constants using an integrating sphere as a light source in the laboratory.

Appl Opt 2013 Apr;52(11):2226-34

State Environmental Protection Key Laboratory of Satellite Remote Sensing, Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, Beijing 100101, China.

A calibration method is introduced to transfer calibration constants from the reference to secondary sunphotometers using a laboratory integrating sphere as a light source, instead of the traditional transferring approach performed at specific calibration sites based on sunlight. The viewing solid angle and spectral response effects of the photometer are taken into account in the transfer, and thus the method can be applied to different types of sunphotometers widely used in the field of atmospheric observation. A laboratory experiment is performed to illustrate this approach for four types of CIMEL CE318 sunphotometers belonging to the aerosol robotic network (AERONET). The laboratory calibration method shows an average difference of 1.4% from the AERONET operational calibration results, while a detailed error analysis suggests that the uncertainty agrees with the estimation and could be further improved. Using this laboratory calibration approach is expected to avoid weather influences and decrease data interruption due to operationally required periodic calibration operations. It also provides a basis for establishing a network including different sunphotometers for worldwide aerosol measurements, based on a single standard calibration reference.
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http://dx.doi.org/10.1364/AO.52.002226DOI Listing
April 2013

Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes.

Biophys J 2012 Mar 6;102(5):1011-21. Epub 2012 Mar 6.

Institute of Molecular Medicine and State Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Life Sciences, Peking University, Beijing, China.

Superoxide flash represents quantal and bursting production of mitochondrial reactive oxygen species (ROS) instigated by transient opening of the mitochondrial permeability transition pore (mPTP). Given their critical role in metabolism, ischemia-reperfusion injury, and apoptosis, characterization of flash properties would be valuable to further mechanistic and physiological studies of this newly discovered mitochondrial phenomenon. Here we developed the flash detector FlashSniper based on segmentation of two-dimensional feature maps extracted from time-lapse confocal image stacks, and on the theory for correcting optical distortion of flash-amplitude histograms. Through large-scale analysis of superoxide flashes in cardiomyocytes, we demonstrated uniform mitochondrial ROS excitability among subsarcolemmal and intermyofibrillar mitochondria, and exponential distribution of intervals between consecutive flash events. Flash ignition displayed three different patterns: an abrupt rise from quiescence (44%), a rise with an exponential foot (27%), or a rise occurring after a pedestal precursor (29%), closely resembling action-potential initiation in excitable cells. However, the optical blurring-corrected amplitudes of superoxide flashes were highly variable, as were their durations, indicating stochastic automaticity of single-mitochondrion ROS excitation. Simultaneous measurement of mitochondrial membrane potential revealed that graded, rather than all-or-none, depolarization mirrored the precursor and the primary peak of the flash. We propose that superoxide flash production is a regenerative process dominated by stochastic, autonomous recruitment of a limited number of units (e.g., mPTPs) in single mitochondria.
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http://dx.doi.org/10.1016/j.bpj.2012.01.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296039PMC
March 2012