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| 1 | p53 upregulated by HIF-la promotes hypoxiainduced G2/M arrest and renal fibrosis in vitro and in vivo显示文摘Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis. | Limin Liu Peng Zhang Ming Bai Lijie He Lei Zhang Ting Liu Zhen Yang Menglu Duan Minna Liu Baojian Liu Rui Du Qi Qian Shiren Sun | 2019 | Journal of Molecular Cell Biology2019，11，5： | 18 |
| 2 | Hypoxia adaptation in the cornea:Current animal models and underlying mechanisms显示文摘The cornea is an avascular,transparent tissue that is essential for visual function.Any disturbance to the corneal transparency will result in a severe vision loss.Due to the avascular nature,the cornea acquires most of the oxygen supply directly or indirectly from the atmosphere.Corneal tissue hypoxia has been noticed to influence the structure and function of the cornea for decades.The etiology of hypoxia of the cornea is distinct from the rest of the body,mainly due to the separation of cornea from the atmosphere,such as prolonged contact lens wearing or closed eyes.Corneal hypoxia can also be found in corneal inflammation and injury when a higher oxygen requirement exceeds the oxygen supply.Systemic hypoxic state during lung diseases or high altitude also leads to corneal hypoxia when a second oxygen consumption route from aqueous humor gets blocked.Hypoxia affects the cornea in multiple aspects,including disturbance of the epithelium barrier function,corneal edema due to endothelial dysfunction and metabolism changes in the stroma,and thinning of corneal stroma.Cornea has also evolved mechanisms to adapt to the hypoxic state initiated by the activation of hypoxia inducible factor(HIF).The aim of this review is to introduce the pathology of cornea under hypoxia and the mechanism of hypoxia adaptation,to discuss the current animal models used in this field,and future research directions. | Kunpeng Pang Anton Lennikov Menglu Yang | 2021 | Animal Models and Experimental Medicine2021，4，4： | 4 |
| 3 | Knockout of butyrophilin subfamily 1 member A1(BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells显示文摘Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.Methods: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ratio.Conclusions: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition. | Liqiang Han Menglu Zhang Zhiyang Xing Danielle N.Coleman Yusheng Liang Juan J.Loor Guoyu Yang | 2020 | Journal of Animal Science and Biotechnology2020，11，4： | 3 |
| 4 | Impact of COVID-2019 on stroke services in China: survey from the Chinese Stroke Association显示文摘Background The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly.We aimed to illustrate how the stroke services were interrupted during the pandemic in China.Methods A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020.Results A total of 415 respondents completed the online survey after informed consent was obtained.Of the respondents,37.8%,35.2%and 27.0%were from mild,moderate and severe epidemic areas,respectively.Overall,the proportion of severe impact(reduction>50%)on the admission of transient ischaemic stroke,acute ischaemic stroke(AIS)and intracerebral haemorrhage(ICH)was 45.0%,32.0%and 27.5%,respectively.Those numbers were 36.9%,27.9%and 22.3%;36.5%,22.1%and 22.6%;and 66.4%,47.5%and 41.1%in mild,moderate and severe epidemic areas,respectively(all p<0.0001).For AIS,thrombolysis was moderate(20%-50%reduction)or severely impacted(>50%),as reported by 54.4%of the respondents,while thrombectomy was 39.3%.These were 44.4%,26.3%;44.2%,39.4%;and 78.2%,56.5%,in mild,moderate and severe epidemic areas,respectively(all p<0.0001).For patients with acute ICH,39.8%reported the impact was severe or moderate for those eligible for surgery who had surgery.Those numbers were 27.4%,39.0%and 58.1%in mild,moderate and severe epidemic areas,respectively.For staff resources,about 20%(overall)to 55%(severe epidemic)of the respondents reported moderate or severe impact on the on-duty doctors and nurses.Conclusion We found a significant reduction of admission for all types of patients with stroke during the pandemic.Patients were less likely to receive appropriate care,for example,thrombolysis/thrombectomy,after being admitted to the hospital.Stroke service in severe COVID-19 epidemic areas,for example,Wuhan,was much more severely impacted compared with other regions in China. | Xia Wang Menglu Ouyang Cheryl Carcel Chen Chen Lingli Sun Jie Yang Yao Zhang Guofang Chen Shoujiang You Yongjun Cao Lu Ma Xin Hu Yi Sui Craig Anderson Lili Song Yongjun Wang David Wang | 2020 | Stroke & Vascular Neurology2020，5，4： | 2 |
| 5 | Multiplex detection of KRAS and BRAF mutations using cationic conjugated polymers显示文摘The mutation detections of KRAS and BRAF genes are of significant importance to predict the responses to anti-cancer therapy and develop new drugs. In this paper, we developed a multi-step fluorescence resonance energy transfer (FRET) assay for multiplex detection of KRAS and BRAF mutations using cationic conjugated polymers (CCP). The newly established detection system could detect as low as 2% mutant DNAs in DNA admixtures. By triggering the emission intensity change of CCP and the dyes labeled in the DNA, four possible statuses (three mutations and one wildtype) can be differentiated in one extension reaction. The detection efficiency of this new method in clinical molecular diagnosis was validated by determining KRAS and BRAF mutations of 51 formalin-fixed paraffin-embedded (FFPE) ovary tissue samples. Furthermore, the result of the CCP-based multi-step FRET assay can be directly visualized under UV light so that no expensive instruments and technical expertise are needed. Thus, the assay provides a sensitive, reliable, cost-effective and simple method for the detection of disease-related gene mutations. | XING BaoLing SONG JinZhao GE SuMei TANG ZhengHua LIU MengLu YANG Qiong Lü FengTing LIU LiBing WANG Shu | 2013 | Chinese Science Bulletin2013，58，8： | 1 |
| 6 | Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa显示文摘Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion. | Sam Enayati Karen Chang Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen | 2024 | Neural Regeneration Research2024，19，11： | 0 |
| 7 | Next-generation finely controlled graded porous antibacterial bioceramics for high-efficiency vascularization in orbital reconstruction显示文摘Eyeball loss due to severe ocular trauma,intraocular malignancy or infection often requires surgical treatment called orbital implant reconstruction to rehabilitate the orbital volume and restore the aesthetic appearance.However,it remains a challenge to minimize the postoperative exposure and infection complications due to the inert nature of conventional orbital implants.Herein,we developed a novel Ca-Zn-silicate bioceramic implant with multi-functions to achieve the expected outcomes.The porous hardystonite(Ca2ZnSi2O7)scaffolds with triply periodic minimal surfaces(TPMS)-based pore architecture and graded pore size distribution from center to periphery(from 500 to 800μm or vice versa)were fabricated through the digital light processing(DLP)technique,and the scaffolds with homogeneous pores(500 or 800μm)were fabricated as control.The graded porous scaffolds exhibited a controlled bio-dissolving behavior and intermediate mechanical strength in comparison with the homogeneous counterparts,although all of porous implants presented significant antibacterial potential against S.aureus and E.coli.Meanwhile,the pore size-increasing scaffolds indicated more substantial cell adhesion,cell viability and angiogenesis-related gene expression in vitro.Furthermore,the gradually increasing pore feature exhibited a stronger blood vessel infiltrating potential in the dorsal muscle embedding model,and the spherical implants with such pore structure could achieve complete vascularization within 4 weeks in the eyeball enucleation rabbit models.Overall,our results suggested that the novel antibacterial hardystonite bioceramic with graded pore design has excellent potential as a next-generation orbital implant,and the pore topological features offer an opportunity for the improvement of biological performances in orbital reconstruction. | Jingyi Wang Yiyu Peng Menglu Chen Xizhe Dai Lixia Lou Changjun Wang Zhaonan Bao Xianyan Yang Zhongru Gou Juan Ye | 2022 | Bioactive Materials2022，7，10： | 0 |
| 8 | Tissue distribution of cadmium and its effect on reproduction in Spodoptera exigua显示文摘Vegetable fields are often contaminated by heavy metals,and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding.In this study,cadmium accumulation in the tissues of S.exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated.Under the stress of different concentrations of cadmium(0.2,3.2,and 51.2 mg kg^(-1)),the cadmium content in each tissue of S.exigua increased in a dose-dependent manner.At the larval stage,the highest cadmium accumulation was found in midgut in all three cadmium treatments,but at the adult stage,the highest cadmium content was found in fat body.In addition,the cadmium content in ovaries was much higher than in testes.When F1S.exigua was stressed by cadmium and the F_(2)generation was not fed a cadmium-containing diet,the larval survival,pupation rate,emergence rate and fecundity of the F_(2)generation were significantly reduced in the 51.2 mg kg^(-1)treatment compared to the corresponding F1generation.Even in the F_(2)generation of the 3.2 mg kg^(-1)treatment,the fecundity was significantly lower than in the parental generation.The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg^(-1)cadmium exposure levels.When only mothers were stressed at the larval stage,the fecundity of the F_(2)generation was significantly lower than that of the F1generation in the 51.2 mg kg^(-1)treatment,and it was also significantly lower than in the 3.2 and 0.2 mg kg^(-1)treatments.The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution. | Honghua Su Menglu Wu Yong Yang Yan Deng Yizhong Yang Qingming Sun | 2024 | Journal of Integrative Agriculture2024，23，1： | 0 |
| 9 | Synthesis of Polycarbonate Diols(PCDLs) via Two-step Process Using CH3COONa as an Effective Catalyst显示文摘 | SONG Menglu YANG Xiangui WANG Gongying | 2018 | Chemical Research in Chinese Universities2018，34，4： | 0 |
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