Publications by authors named "Kangjun Zhang"

6 Publications

  • Page 1 of 1

IP-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion.

Nat Commun 2021 04 28;12(1):2461. Epub 2021 Apr 28.

School of Life Sciences, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

COP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1-CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2 mice with partially disrupted binding of IP, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP-assisted CSN-COP1 competition. Deregulation of the IP-CSN-CRL4-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.
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http://dx.doi.org/10.1038/s41467-021-22941-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080631PMC
April 2021

Delayed application of silver nanoparticles reveals the role of early inflammation in burn wound healing.

Sci Rep 2020 04 14;10(1):6338. Epub 2020 Apr 14.

Department of Surgery, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China.

Burn injury is common, and antimicrobial agents are often applied immediately to prevent wound infection and excessive inflammatory response. Although inflammation is essential for clearing bacteria and creating an environment conducive to the healing process, it is unclear what time-frame inflammation should be present for optimal wound healing. This study critically investigated the role of early inflammation in burn wound healing, and also revealed the molecular mechanisms underlying the pro-healing effects of silver nanoparticles (AgNPs). We created a burn injury mouse model using wild-type and Smad3-/- mice, which were topically treated with AgNPs at different post-burn days, and examined the healing processes of the various groups. We also delineated the molecular pathways underlying the anti-inflammation and pro-healing effects of AgNPs by morphological and histological analysis, immuno-histochemistry, and western blotting. Our results showed that (1) AgNPs regulated pro-inflammatory cytokine IL-6 production of keratinocytes and neutrophils infiltration through KGF-2/p38 signaling pathway, (2) Topical AgNPs treatment immediately after burn injury significantly supressed early inflammation but resulted in delayed healing, (3) A short delay in AgNPs application (post-burn day 3 in our model) allowed early inflammation in a controlled manner, and led to optimal burn wound healing. Thus, our current study showed that some degree of early inflammation was beneficial, but prolonged inflammation was detrimental for burn wound healing. Further evaluation and clinical translation of this finding is warranted.
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http://dx.doi.org/10.1038/s41598-020-63464-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156632PMC
April 2020

Author Correction: Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome in Shaanxi Province, China, 2005-2016.

Sci Rep 2018 Apr 13;8(1):6234. Epub 2018 Apr 13.

Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, 710061, China.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-24102-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897451PMC
April 2018

Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome in Shaanxi Province, China, 2005-2016.

Sci Rep 2018 01 15;8(1):749. Epub 2018 Jan 15.

Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, 710061, China.

Hemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis. Each year worldwide, 60,000-100,000 HFRS human cases are reported in more than seventy countries with almost 90% these cases occurring in China. Shaanxi Province in China has been among the most seriously affected areas since 1955. During 2009-2013, Shaanxi reported 11,400 human cases, the most of all provinces in China. Furthermore, the epidemiological features of HFRS have changed over time. Using long-term data of HFRS from 2005 to 2016, we carried out this retrospective epidemiological study combining ecological assessment models in Shaanxi. We found the majority of HFRS cases were male farmers who acquired infection in Guanzhong Plain, but the geographic extent of the epidemic has slowly spread northward. The highest age-specific attack rate since 2011 was among people aged 60-74 years, and the percentage of HFRS cases among the elderly increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS vaccination to people older than 60 years to better protect against the disease. Multivariate analysis revealed artificial area, cropland, pig and population density, GDP, and climate conditions (relative humidity, precipitation, and wind speed) as significant risk factors in the distribution of HFRS.
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http://dx.doi.org/10.1038/s41598-017-18819-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768775PMC
January 2018

Biphasic Synergistic Gel Materials with Switchable Mechanics and Self-Healing Capacity.

Angew Chem Int Ed Engl 2017 10 18;56(43):13464-13469. Epub 2017 Sep 18.

Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, 37 Xueyuan Rd, Beijing, 100191, P. R. China.

A fabrication strategy for biphasic gels is reported, which incorporates high-internal-phase emulsions. Closely packed micro-inclusions within the elastic hydrogel matrix greatly improve the mechanical properties of the materials. The materials exhibit excellent switchable mechanics and shape-memory performance because of the switchable micro- inclusions that are incorporated into the hydrogel matrix. The produced materials demonstrated a self-healing capacity that originates from the noncovalent effect of the biphasic heteronetwork. The aforementioned characteristics suggest that the biphasic gels may serve as ideal composite gel materials with validity in a variety of applications, such as soft actuators, flexible devices, and biological materials.
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http://dx.doi.org/10.1002/anie.201707239DOI Listing
October 2017

Highly Stretchable, Shape Memory Organohydrogels Using Phase-Transition Microinclusions.

Adv Mater 2017 Sep 21;29(33). Epub 2017 Jun 21.

Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, Beijing, 100191, P. R. China.

Shape memory effect in polymer materials has attracted considerable attention due to its promising applications in a variety of fields. However, shape memory polymers prepared by conventional strategy suffer from a common problem, in which high strain capacity and excellent shape memory behavior cannot be simultaneously achieved. This study reports a general and synergistic strategy to fabricate high-strain and tough shape memory organohydrogels that feature binary cooperative phase. The phase- transition micro-organogels and elastic hydrogel framework act synergistically to provide excellent thermomechanical performance and shape memory effect. During shape memory process, the organohydrogels exhibit high strain capacity, featuring fully recoverable stretching deformation by up to 2600% and compression by up to 85% beneath a load ≈20 times the organohydrogel's weight. Furthermore, owing to the micro-organogel and hydrogel heterostructures, the interfacial tension derived from heterophases dominates the shape recovery of the organohydrogel material. Simple processing and smart surface patterning of the shape memory behavior and multiple shape memory effects can also be realized. Meanwhile, these organohydrogels are also nonswellable in water and oil, which is important for multimedia applications.
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http://dx.doi.org/10.1002/adma.201701695DOI Listing
September 2017
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