Publications by authors named "Zhihui Gao"

47 Publications

The complete chloroplast genome sequence of the medicinal plant .

Mitochondrial DNA B Resour 2021 9;6(8):2324-2325. Epub 2021 Jul 9.

College of Life Sciences, Shanxi Datong University, Datong, China.

, known as a traditional Chinese herbal medicine, is a perennial plant of Polygonaceae wildly distributed in China. The complete chloroplast (cp) genome of was assembled and analyzed in this study. The length of the circular genome is 159,741 bp, with a rich GC content of 41.3%. The cp genome structure consists of a large single-copy region (LSC 84,432 bp), a small single-copy region (SSC 13,073 bp) and a pair of inverted repeat regions (IR 31,118 bp). The complete genome encodes 130 genes, including 85 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Phylogenetic analysis indicated that is most related to
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http://dx.doi.org/10.1080/23802359.2021.1950064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274529PMC
July 2021

Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis.

J Transl Med 2021 05 30;19(1):229. Epub 2021 May 30.

Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China.

Background: There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression.

Methods: CC stem cells (CD133CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results.

Results: Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice.

Conclusion: Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells.
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http://dx.doi.org/10.1186/s12967-021-02872-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165805PMC
May 2021

miR-9-5p promotes wear-particle-induced osteoclastogenesis through activation of the SIRT1/NF-κB pathway.

3 Biotech 2021 Jun 9;11(6):258. Epub 2021 May 9.

Department of Orthoped, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004 Ningxia Province China.

To explore the potential function of miR-9-5p in wear-particle-induced osteoclastogenesis, we examined the expression of SIRT1 and miR-9-5p in particle-induced osteolysis (PIO) mice calvariae and polyethylene (PE)-induced RAW 264.7 cells and found that SIRT1 expression was downregulated while miR-9-5p expression was upregulated in both models. We then verified that miR-9-5p targets SIRT1. miR-9-5p was found to promote PE-induced osteoclast formation from RAW 264.7 cells by staining and detection of osteoclast markers, and miR-9-5p activation of the SIRT1/NF-kB signaling pathway was found in cells by detecting the expression of SIRT1/NF-kB pathway-related proteins and rescue assays. In conclusion, we found that miR-9-5p activated the SIRT1/NF-κB pathway to promote wear-particle-induced osteoclastogenesis. miR-9-5p may be a useful therapeutic target for PIO remission and treatment.
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http://dx.doi.org/10.1007/s13205-021-02814-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107064PMC
June 2021

The role of miR-27b-3p/HOXA10 axis in the pathogenesis of endometriosis.

Ann Palliat Med 2021 Mar;10(3):3162-3170

Department of Gynecology and Oncology, Xinxiang Central Hospital, Xinxiang, China.

Background: To explore the effects of microRNA (miR)-27b-3p-mediated homeobox A10 (HOXA10) on the proliferation, migration, and invasion of endometriosis cells (hEM15A).

Methods: First, quantitative polymerase chain reaction (qPCR) was performed for the measurement of miR-27b-3p and HOXA10 expression in hEM15A cells and human embryonic stem cells (hESC). Then, the targeted relationship of miR-27b-3p with HOXA10 was verified by conducting a dual-luciferase reporter experiment. Subsequently, qPCR and western blot were performed to determine the effect of miR-27b-3p on HOXA10 expression. Finally, Cell Counting Kit-8, Transwell, and scratch assays were employed to determine the effects of miR-27b-3p and HOXA10 on the proliferative, migratory, and invasive abilities of hEM15A cells.

Results: In hEM15A cells, miR-27b-3p expression was increased and showed a negative correlation with the expression of HOXA10 (P<0.05). The dual-luciferase reporter experiment confirmed that miR-27b-3p targeted the HOXA10 gene. Furthermore, qPCR and western blotting showed that miR-27b-3p regulated the expression of HOXA10. The proliferation, migration, and invasion abilities of hEM15A cells was significantly inhibited by suppressing miR-27b-3p expression or overexpressing HOXA10 (P<0.05). Meanwhile, concurrent overexpression of miR-27b-3p and HOXA10 did not affect hEM15A cell activity (P>0.05).

Conclusions: Upregulation of miR-27b-3p can suppress HOXA10 expression, resulting in the enhancement of hEM15A cell proliferation, migration, and invasion.
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http://dx.doi.org/10.21037/apm-21-343DOI Listing
March 2021

Carboxyl-terminal polypeptide fragment of MUC16 combing stathmin1 promotes gallbladder cancer cell migration and invasion.

Med Oncol 2020 Nov 16;37(12):114. Epub 2020 Nov 16.

General Surgery Department, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, China.

CA-125, coded by MUC16 gene, is responsible to many kinds of tumor metastasis. However, the related mechanism remains unclear. We have established a novel manner to reveal gallbladder cancer metastasis related to serum CA-125 levels through the C-terminal polypeptide of MUC16 gene production. MUC16 C-terminal polypeptide significantly promoted gallbladder cancer cell migration and invasion in vitro. Mass spectrum indicated that interaction of MUC16 C-terminal fragment with the C-terminal domain of stathmin1 inhibited the phosphorylation of stathmin1 to promote the combination with tubulin. Stathmin1 knockdown inhibited the migration and invasion of gallbladder cancer cells in vitro and lung metastasis in vivo induced by MUC16 C-terminal polypeptide. The high expression level of MUC16c consistent with stathmin1 was also confirmed in gallbladder cancer tissues. Our study revealed the underlying mechanism of gallbladder cancer metastasis related to CA-125 levels, which was beneficial for CA-125 in gallbladder cancer diagnose and therapy.
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http://dx.doi.org/10.1007/s12032-020-01438-xDOI Listing
November 2020

N-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Cell Death Dis 2020 10 24;11(10):911. Epub 2020 Oct 24.

Department of Gynecology, Third Affiliated Hospital Guangzhou Medical University, 510080, Guangdong, China.

N6-methyladenosine (mA) serves as the most common and conserved internal transcriptional modification. However, the roles of mA on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the mA profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3'-Untranslated Region (3'-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a mA reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated mA modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.
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http://dx.doi.org/10.1038/s41419-020-03071-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585578PMC
October 2020

Simultaneous determination of multiple active 2-(2-phenylethyl)chromone analogues in agarwood by HPLC, QAMS, and UPLC-MS.

Phytochem Anal 2021 May 16;32(3):412-422. Epub 2020 Sep 16.

National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.

Introduction: Chromones are the major constituents of agarwood and are considered to be directly related to its quality. Agarotetrol, a chromone derivative, is a Chinese Pharmacopoeia content detection index. However, comprehensive high-performance liquid chromatography (HPLC), quantitative analysis of multiple components by a single marker (QAMS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) analyses of this pharmacopeial plant material have never been performed. Moreover, reports regarding the separation and detection of multiple active 2-(2-phenylethyl)chromone analogues from this plant material are surprisingly scarce.

Objective: To establish a simple, reliable, and effective HPLC method utilising both diode array and MS detection for the simultaneous determination of multiple active chromone analogues in agarwood.

Methods: Four 2-(2-phenylethyl)chromones were isolated from methanol extracts of agarwood. After optimising the extraction, separation, and analytical conditions, validation of the developed analytical method indicated good linearity, satisfactory precision, and good recovery. On this basis, a method for the quantitative analysis of multiple components by a single marker was established. The four 2-(2-phenylethyl)chromones were identified by nuclear magnetic resonance spectroscopic analysis and UPLC coupled to electrospray ionisation quadrupole-time-of-flight MS.

Conclusions: The behaviour of the chromones characterised by MS fragmentation indicated a loss of molecular CO and the formation of m/z 121 compounds by the cleavage of CH -CH bonds between the chromone and phenyl moieties. Three detection methods were successfully used in this study for agarwood detection, and this protocol may potentially be used as a tool for the quality control of agarwood.
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http://dx.doi.org/10.1002/pca.2989DOI Listing
May 2021

Localization of quantitative trait loci for cucumber fruit shape by a population of chromosome segment substitution lines.

Sci Rep 2020 07 3;10(1):11030. Epub 2020 Jul 3.

State Key Laboratory of Crop Biology; Shandong Collaborative Innovation Center of Fruit & Vegetable Quality and Efficient Production; Key Laboratory of Biology and Genetic Improvement of Horticultural Crops in Huang-Huai Region, Ministry of Agriculture; College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, 271018, Shandong, People's Republic of China.

Cucumber fruit shape, a significant agronomic trait, is controlled by quantitative trait loci (QTLs). Feasibility of chromosome segment substitution lines (CSSLs) is well demonstrated to map QTLs, especially the minor-effect ones. To detect and identify QTLs with CSSLs can provide new insights into the underlying mechanisms regarding cucumber fruit shape. In the present study, 71 CSSLs were built from a population of backcross progeny (BCF) by using RNS7 (a round-fruit cucumber) as the recurrent parent and CNS21 (a long-stick-fruit cucumber) as the donor parent in order to globally detect QTLs for cucumber fruit shape. With the aid of 114 InDel markers covering the whole cucumber genome, 21 QTLs were detected for fruit shape-related traits including ovary length, ovary diameter, ovary shape index, immature fruit length, immature fruit diameter, immature fruit shape index, mature fruit length, mature fruit diameter and mature fruit shape index, and 4 QTLs for other traits including fruit ground and flesh color, and seed size were detected as well. Together our results provide important resources for the subsequent theoretical and applied researches on cucumber fruit shape and other traits.
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http://dx.doi.org/10.1038/s41598-020-68312-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334212PMC
July 2020

Prediction Efficacy for Clinical Outcome of Prognostic Nutritional Index in Patients with Resectable Biliary Tract Cancer Depends on Sex and Obstructive Jaundice Status.

Ann Surg Oncol 2021 Jan 16;28(1):430-438. Epub 2020 Jun 16.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: The Prognostic Nutritional Index (PNI), a marker of nutritional status and systemic inflammation, is a proven prognostic biomarker in some cancers. The predictive value of PNI in biliary tract cancer (BTC) has not been established.

Objective: The aim of this study was to determine the relationship between the PNI and outcomes of resectable BTC.

Methods: In total, 430 patients with stage I-III resectable BTC [gallbladder cancer (GBC), n = 212; cholangiocarcinoma (CHO), n = 218] who had attended Fudan University Zhongshan Hospital were enrolled. The relationship between the PNI and clinical outcomes was evaluated both in the whole cohort and in selected subgroups.

Results: Eligible patients were classified into PNI-low (PNI < 45) and PNI-high (PNI ≥ 45) groups. The PNI-low group had significantly worse overall survival (OS) in both the whole cohort (p = 0.002) and in the GBC subgroup (p = 0.001), but had similar OS as the PNI-high group in the CHO subgroup (p = 0.328). Multivariate analysis revealed that low PNI is an independent risk factor for worse survival in GBC (hazard ratio 1.623, 95% confidence interval 1.063-2.480, p = 0.026). PNI was found to predict clinical outcome in women (p < 0.001) and patients without obstructive jaundice (p = 0.017) with GBC, but was not a prognostic factor in any subgroup with CHO. The estimated area under the time-dependent receiver operating characteristic curve was significantly greater when TNM stage was combined with PNI in women with GBC.

Conclusions: PNI is an independent predictor of OS in GBC, but not in CHO. It has no prognostic value in men with GBC or patients with obstructive jaundice.
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http://dx.doi.org/10.1245/s10434-020-08728-8DOI Listing
January 2021

MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth.

Exp Cell Res 2020 09 2;394(1):112118. Epub 2020 Jun 2.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Institute, Fudan University, Shanghai, China. Electronic address:

The MUC16 C-terminal (MUC16c) level is associated with tumor serum CA-125 levels, however, the roles remain unclear in gallbladder carcinoma (GBC). In this study, we found that MUC16c promoted glucose uptake and glycolysis for GBC cell proliferation. Mass spectrometry analysis suggested that MUC16c could combine with aldolase. The ALDOC mRNA and protein are overexpressed in GBC tumors. The IHC results also showed the consistent up-regulation of. ALDOC and MUC16c level in GBC tumor tissues than in peritumor tissues. We determined that MUC16c combining with ALDOC promoted ALDOC protein stability and disrupted the ability of ALDOC sensing glucose deficiency, which activated AMPK pathway and increased GBC cell proliferation. ALDOC knockdown significantly inhibited the glucose uptake and glycolysis induced by MUC16c. Our study established important roles of MUC16c promoting GBC cell glycolysis and proliferation and revealed the underlying mechanism of CA-125-related heavy tumor metabolic burden in GBC.
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http://dx.doi.org/10.1016/j.yexcr.2020.112118DOI Listing
September 2020

Molecular Mechanism Underlying Mechanical Wounding-Induced Flavonoid Accumulation in T. Chen, an Endangered Tree That Produces Chinese Rosewood.

Genes (Basel) 2020 04 28;11(5). Epub 2020 Apr 28.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Chinese Peking Union Medical College, Beijing 100193, China.

, a critically endangered tree species, produces heartwood containing a vast variety of flavonoids. This heartwood, also known as Chinese rosewood, has high economic and medicinal value, but its formation takes several decades. In this study, we showed that discolored wood induced by pruning displays similar color, structure, and flavonoids content to those of natural heartwood, suggesting that wounding is an efficient method for inducing flavonoid production in . Transcriptome analysis was performed to investigate the mechanism underlying wounding-induced flavonoids production in heartwood. Wounding upregulated the expression of 90 unigenes, which covered 19 gene families of the phenylpropanoid and flavonoid pathways, including PAL, C4H, 4CL, CHS, CHI, 6DCS, F3'5'H, F3H, FMO, GT, PMAT, CHOMT, IFS, HI4'OMT, HID, IOMT, I2'H, IFR, and I3'H. Furthermore, 47 upregulated unigenes were mapped to the biosynthesis pathways for five signal molecules (ET, JA, ABA, ROS, and SA). Exogenous application of these signal molecules resulted in the accumulation of flavonoids in cell suspensions of , supporting their role in wounding-induced flavonoid production. Insights from this study will help develop new methods for rapidly inducing the formation of heartwood with enhanced medicinal value.
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http://dx.doi.org/10.3390/genes11050478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291145PMC
April 2020

3D laparoscopic common bile duct exploration versus 2D in choledocholithiasis patients: a propensity score analysis.

Surg Endosc 2021 02 20;35(2):819-825. Epub 2020 Mar 20.

Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China.

Background: This study was designed to investigate whether 3D laparoscopic common bile duct (LCBDE) could improve surgical outcomes in choledocholithiasis patients compared with 2D LCBDE.

Method: Propensity score-matched analysis was performed to balance the bias in baseline characteristic between two groups.

Results: 213 patients underwent 3D LCBDE and 212 patients receiving 2D LCBDE were enrolled in this study. The operation time and blood loss in 3D group were significantly less than that in 2D group. After propensity score matching, a total of 114 paired cases were selected from the two groups. The operation time and blood loss in 3D group remain significantly lower than in 2D group. In the end, the subgroup analysis based on abdominal adhesion level was performed and it was observed that for patients with adhesion level 1 and level 2, 3D surgery could obviously decrease the operation time and intraoperative blood loss.

Conclusions: 3D LCBDE would significantly reduce operation time, blood loss, and conversion rate to laparotomy in choledocholithiasis patients versus 2D LCBDE. For patients with abdominal adhesions level 1 and level 2, 3D LCBDE could provide better surgical outcomes than 2D LCBDE.
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http://dx.doi.org/10.1007/s00464-020-07453-3DOI Listing
February 2021

Seroprevalence of Toxoplasma gondii infection in sheep in Inner Mongolia Province, China.

Parasite 2020 19;27:11. Epub 2020 Feb 19.

Inner Mongolia KingGoal Technology Service Co., Ltd., Hohhot 010010, PR China.

Toxoplasma gondii is an important zoonotic parasite that can infect almost all warm-blooded animals, including humans, and infection may result in many adverse effects on animal husbandry production. Animal husbandry in Inner Mongolia is well developed, but data on T. gondii infection in sheep are lacking. In this study, we determined the seroprevalence and risk factors associated with the seroprevalence of T. gondii using an indirect enzyme-linked immunosorbent assay (ELISA) test. A total of 1853 serum samples were collected from 29 counties of Xilin Gol League (n = 624), Hohhot City (n = 225), Ordos City (n = 158), Wulanchabu City (n = 144), Bayan Nur City (n = 114) and Hulunbeir City (n = 588). The overall seroprevalence of T. gondii was 15.43%. Risk factor analysis showed that seroprevalence was higher in sheep ≥12 months of age (21.85%) than that in sheep <12 months of age (10.20%) (p < 0.01). Seroprevalence was higher in male sheep (18.76%) than females (12.80%) (p < 0.01). Barn-feeding sheep (23.13%) had higher prevalence than grazing sheep (10.94%) (p < 0.01). The seroprevalence was significantly different in different districts (p < 0.01). This study shows that sheep are exposed to T. gondii in Inner Mongolia, and provides a data reference for public health and disease control.
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http://dx.doi.org/10.1051/parasite/2020008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029707PMC
November 2020

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer.

Cancer Sci 2020 Mar 3;111(3):817-825. Epub 2020 Feb 3.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Recent studies have reported that tumor-infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine-based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine-based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM-activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell-related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine-based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.
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http://dx.doi.org/10.1111/cas.14302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060478PMC
March 2020

Landscape of distant metastasis mode and current chemotherapy efficacy of the advanced biliary tract cancer in the United States, 2010-2016.

Cancer Med 2020 02 26;9(4):1335-1348. Epub 2019 Dec 26.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed.

Method: A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias.

Result: The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P < .05 in all the subtypes) where the multi-metastasis and distant lymph node (dLN) only always indicated the worst and best prognosis, respectively. Chemotherapy presented the most significant survival impact with the lowest hazard ratio by multivariate cox model and still provided a survival improvement after PSM (all P < .001) in all subtypes. However, the median months manifested different between patients with and without chemotherapy among the subtypes (ICC, from 5 to 9; PHCC, from 6 to 10; AVC, from 4 to 9; GBC, from 6 to 7; DCC from 6 to 8).

Conclusion: We provided a landscape about the detailed DM mode of the advanced BTC in a large population, found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes.
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http://dx.doi.org/10.1002/cam4.2794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013071PMC
February 2020

Hydrogen peroxide burst triggers accumulation of jasmonates and salicylic acid inducing sesquiterpene biosynthesis in wounded Aquilaria sinesis.

J Plant Physiol 2019 Mar - Apr;234-235:167-175. Epub 2019 Feb 20.

Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College (Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization), Haikou, 570311, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address:

Agarwood, a non-timber fragrant wood, is produced in wounded Aquilaria trees and widely used in perfume, incense, and medicine. Sesquiterpene is one of its main active compounds. It has been demonstrated that hydrogen peroxide (HO) plays a role in promoting agarwood sesquiterpene biosynthesis, but little is known about its signaling pathway. In this study, the pruning of actively growing saplings of A. sinensis resulted in an HO burst and the accumulation of jasmonic acid (JA), salicylic acid (SA), and ethylene (ET), which was followed by the up-regulation of sesquiterpene synthase and the production of sesquiterpene in the pruned stems. This process could be enhanced by absorbed HO and inhibited by an HO scavenger (ascorbate, AsA) in pruned stems, although the concentration of ET and transcription of ET-related synthase genes remained unaffected. These results confirmed that the HO burst in wounded stems triggered JA and SA accumulation to promote agarwood sesquiterpene biosynthesis. ET was also activated by injury that was independent with HO. All results excavated a full-scale signaling transduction nets among multiple stress signals during wound-induced agarwood production in A. sinensis and provide a new insight into improving the artificial technology of agarwood production.
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http://dx.doi.org/10.1016/j.jplph.2019.02.006DOI Listing
March 2019

Progress of immune checkpoint therapy in the clinic (Review).

Oncol Rep 2019 Jan 24;41(1):3-14. Epub 2018 Oct 24.

Department of Hepatobiliary Surgery, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China.

Cancer cells can escape antitumor immune responses by exploiting inhibitory immune checkpoints. Immune checkpoint therapy, mainly including anti‑CTLA‑4 therapy and anti‑PD‑1/PD‑L1 therapy, can enhance antitumor immune responses by blocking the inhibitory signals of the immune system. This therapy has produced clinical advances in a fraction of patients. Deeper insight into the tumor microenvironment and immune checkpoint inhibitors will improve this therapy. Here, we review immune checkpoint inhibitors that prevent tumor immune escape and recent clinical studies of immune checkpoint therapy. We also compare the efficacy of different combination immunotherapies, describe how the relationship between the gut microbiome and immune system can determine the therapeutic outcomes for immune checkpoint inhibitors and introduce several novel immune checkpoints that are potential targets for antitumor immunotherapy in the future.
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http://dx.doi.org/10.3892/or.2018.6819DOI Listing
January 2019

GRP75 modulates oncogenic Dbl-driven endocytosis derailed via the CHIP-mediated ubiquitin degradation pathway.

Cell Death Dis 2018 09 24;9(10):971. Epub 2018 Sep 24.

Department of Cell Biology, School of Medicine, Nankai University, Tianjin, China.

Chaperone-assisted proteasome degradation of oncogenic protein acts as an upstream signal controlling tumorigenesis and progression. The understanding of the co-regulation of chaperone and oncoprotein of endocytosis pathways is extremely limited. In this study, we showed for the first time that proto-Dbl (dbl proto-oncogene product) is co-enriched with mitochondrial chaperone GRP75 in endocytosis vesicles from ovarian cancer cells. onco-Dbl, produced by oncogenic mutation/degradation of proto-Dbl, markedly enhanced cellular macropinocytosis but suppressed clathrin-mediated endocytosis and clathrin-independent endocytosis pathways, presenting a derailed endocytosis phenotype. GRP75 was associated with proto-Dbl inside cells and modulated Dbl-driven endocytosis derailed by a co-regulatory mode. In spite of not being a component of the Hsc70/Hsp90/proto-Dbl complex, the degradation of proto-Dbl was promoted by GRP75 through the CHIP-mediated ubiquitin-proteasome pathway, of which GRP75 acts as a cooperator with CHIP but also acts as a competitor to Hsc70 and Hsp90 in the multiple chaperones-assisted pro-folding/pro-degradation machinery. Knockdown or inhibition of GRP75 attenuated proto-Dbl degradation and reduced the onco-Dbl level, which differentially impaired Rho GTPases activation and therefore shifted the endocytosis-derailed phenotype. Our data uncovered a novel GRP75-Dbl endocytosis regulatory axis and provided an alternative using chaperone inhibitor to shut down the oncoprotein-driven endocytosis derailment mechanism.
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http://dx.doi.org/10.1038/s41419-018-1039-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155137PMC
September 2018

Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells.

Int J Nanomedicine 2018 30;13:4895-4911. Epub 2018 Aug 30.

Department of Cell Biology, School of Medicine, Nankai University, Tianjin, People's Republic of China,

Background: Successful implementation of gene therapy heavily relies on efficiently delivering genetic materials and specific targeting into cells. Oncogene-driven endocytosis stimulates nutrient uptake and also develops an endocytosis-mediated defense against therapeutic agents. Cell-penetrating peptides, typically HIV-Tat, are well known for efficient delivery of nucleic acid drugs but lack targeting specificity. Various passive targeting strategies were pursued to enhance the tumor targeting efficiency; however, they are still limited by complicated cellular endocytosis routes and the heterogeneity of cancer types.

Methods: Tat/pDNA complexes were noncovalently compacted and their physiochemical properties were determined. The siRNA pool and pLV-RNAi-GFP lentivirus were used to knock down oncogene (originally isolated from diffuse B-cell lymphoma) expression, and its overexpression was performed by plasmid transient transfection. The cellular uptake of fluorescent ligands was quantified by confocal imaging and flow cytometry analysis. The transgene efficiency was determined by the Luciferase expression assay. Rho GTPase activation was checked by the GST-Rho GTPase-binding domain pull-down assay.

Results: pGL3 plasmid DNA was noncovalently compacted with the Tat peptide into nano-size complexes at high N/P ratios. Macropinocytosis, a clathrin- and caveolin-independent endocytosis process, was shown to contribute to the uptake of middle-sized (∼600 nm) Tat/pGL3 complexes. Cell-type-specific variation in macropinocytosis was essentially controlled by the action of the oncogene. Onco-Dbl presentation constantly induced a high level of macropinocytosis activity in ovarian cancer cells. Onco-Dbl overexpression hyperstimulated macropinocytosis enhancement in cells mainly through actin cytoskeleton reorganization mediated by the PH domain and Rac1 activation. The Dbl-driven Rho GTPase signaling collectively determined the cell-type-specific macropinocytosis phenotype.

Conclusion: Such an aspect can be exploited to selectively confer targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells. Our work provides a novel alternative for targeted delivery of cell-penetrating peptide-based nucleic acid drugs into certain tumor types if specific endocytosis pathways are used.
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http://dx.doi.org/10.2147/IJN.S171361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122892PMC
October 2018

Genome Size, Molecular Phylogeny, and Evolutionary History of the Tribe Aquilarieae (Thymelaeaceae), the Natural Source of Agarwood.

Front Plant Sci 2018 29;9:712. Epub 2018 May 29.

Forest Biotech Laboratory, Department of Forest Management, Faculty of Forestry, Universiti Putra Malaysia (UPM Serdang), Seri Kembangan, Malaysia.

The tribe Aquilarieae of the family Thymelaeaceae consists of two genera, and , with a total of 30 species, distributed from northeast India, through southeast Asia and the south of China, to Papua New Guinea. They are an important botanical resource for fragrant agarwood, a prized product derived from injured or infected stems of these species. The aim of this study was to estimate the genome size of selected species and comprehend the evolutionary history of Aquilarieae speciation through molecular phylogeny. Five non-coding chloroplast DNA regions and a nuclear region were sequenced from 12 and three species. Phylogenetic trees constructed using combined chloroplast DNA sequences revealed relationships of the studied 15 members in Aquilarieae, while nuclear ribosomal DNA internal transcribed spacer (ITS) sequences showed a paraphyletic relationship between species from Indochina and Malesian. We exposed, for the first time, the estimated divergence time for Aquilarieae speciation, which was speculated to happen during the Miocene Epoch. The ancestral split and biogeographic pattern of studied species were discussed. Results showed no large variation in the 2C-values for the five species (1.35-2.23 pg). Further investigation into the genome size may provide additional information regarding ancestral traits and its evolution history.
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http://dx.doi.org/10.3389/fpls.2018.00712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987174PMC
May 2018

Particle-induced SIRT1 downregulation promotes osteoclastogenesis and osteolysis through ER stress regulation.

Biomed Pharmacother 2018 Aug 25;104:300-306. Epub 2018 May 25.

Department of Orthopedics, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address:

Background: Sirtuin 1 (SIRT1) downregulation has been found to be induced by wear particles in aseptic prosthesis loosening (APL). Osteoclastogenesis and osteoclast activation are the main pathological factors associated with APL. However, whether SIRT1 downregulation contributes to the formation and activation of osteoclasts through the induction of endoplasmic reticulum (ER) stress is unclear.

Methods: To address this, an osteolysis mouse model was used in which animals were treated with the SIRT1 activator, resveratrol (RES), or an ER stress inhibitor, 4-PBA, for two weeks. Osteolysis, osteoclastogenesis, and morphologic alteration of calvariae were observed by toluidine blue, TRAP, and H&E staining. SIRT1 expression and ER stress were evaluated by western blot analysis. In vitro, mouse macrophage RAW 264.7 cells were treated with polyethylene (PE) particles alone or combined with either RES or 4-PBA, and SIRT1 expression and ER stress were measured using western blot assays. Osteoclast differentiation was determined through TRAP staining. Osteoclast activation was evaluated by culturing osteoclast cells on bone slices followed by toluidine blue staining. Mechanistically, osteoclastogenesis-related MAPK activation, NFATc1 and c-Fos expression, and NF-κB translocation were determined.

Results: Both in vivo and in vitro experimental results indicated that PE particles induced SIRT1 downregulation and enhanced ER stress. SIRT1 activator RES and ER stress inhibitor 4-PBA significantly suppressed PE particle-induced osteoclast differentiation and osteolysis. In vitro experimental results showed that 4-PBA suppressed PE particle-induced ERK1/2, p38, and JNK activation, NFATc1 and c-Fos upregulation, as well as NF-κB p65 nucleus translocation.

Conclusions: PE particle-induced downregulation of SIRT1 enhances ER stress and promotes osteoclast proliferation and bone resorption through regulation of c-Fos, NFATc1, and the MAPK and NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.biopha.2018.05.030DOI Listing
August 2018

Mitochondria chaperone GRP75 moonlighting as a cell cycle controller to derail endocytosis provides an opportunity for nanomicrosphere intracellular delivery.

Oncotarget 2017 Aug 19;8(35):58536-58552. Epub 2017 Apr 19.

Department of Biochemistry & Cell Biology, School of Medicine, Nankai University, Tianjin, China.

Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking. In this study, GRP75, a mitochondria matrix chaperone, was discovered to be highly expressed in mitotic cancer cells. Using synchronized cell models and the GRP75 gene knockdown and ectopic overexpression strategy, we showed that: (1) clathrin-mediated endocytosis (CME) was inhibited whereas clathrin-independent endocytosis (CIE) was unchanged or even up-regulated in the cell cycle M-phase; (2) GRP75 inhibited CME but promoted CIE in the M-phase, which is largely due to its high expression in cancer cell mitochondria; (3) GRP75 targeting by its small molecular inhibitor MKT-077 enhanced cell cycle G1 phase-privileged CME, which provides an opportunity for intracellular delivery of nanomicrospheres sized from 40 nm to 100 nm. Together, our results revealed that GRP75 moonlights as a cell cycle controller and endocytosis regulator in cancer cells, and thus has potential as a novel interference target for nanoparticle drugs delivery into dormant cancer cells.
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http://dx.doi.org/10.18632/oncotarget.17234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601673PMC
August 2017

Assessment of swallowability and palatability of oral dosage forms in children: Report from an M-CERSI pediatric formulation workshop.

Int J Pharm 2018 Feb 24;536(2):570-581. Epub 2017 Aug 24.

Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, Ernst Moritz Arndt University Greifswald, Felix-Hausdorff-Strasse 3, 17489 Greifswald, Germany.

The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI). A session at the workshop was dedicated to acceptability assessments and focused on two major elements that affect the overall acceptability of oral medicines, namely swallowability and palatability. The session started with presentations to provide an overview of literature, background and current state on swallowability and palatability assessments. Five parallel breakout discussions followed the presentations on each element, focusing on three overarching themes, risk-based approaches, methodology and product factors. This article reports the key outcomes of the workshop related to swallowability and palatability assessments.
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http://dx.doi.org/10.1016/j.ijpharm.2017.08.088DOI Listing
February 2018

Stathmin decreases cholangiocarcinoma cell line sensitivity to staurosporine-triggered apoptosis via the induction of ERK and Akt signaling.

Oncotarget 2017 Feb;8(9):15775-15788

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Cholangiocarcinoma is a rare, but highly fatal malignancy. However, the intrinsic mechanism involved in its tumorigenesis remains obscure. An urgent need remains for a promising target for cholangiocarcinoma biological therapies. Based on comparative proteomical technologies, we found 253 and 231 different spots in gallbladder tumor cell lines and cholangiocarcinoma cell lines, respectively, relative to non-malignant cells. Using Mass Spectrometry (MS) and database searching, we chose seven differentially expressed proteins. High Stathmin expression was found in both cholangiocarcinoma and gallbladder carcinoma cells. Stathmin expression was validated using immunohistochemistry and western blot in cholangiocarcinoma tissue samples and peritumoral tissue. It was further revealed that high Stathmin expression was associated with the repression of staurosporine-induced apoptosis in the cholangiocarcinoma cell. Moreover, we found that Stathmin promoted cancer cell proliferation and inhibited its apoptosis through protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling. Integrin, β1 appears to serve as a partner of Stathmin induction of ERK and Akt signaling by inhibiting apoptosis in the cholangiocarcinoma cell. Understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma.
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http://dx.doi.org/10.18632/oncotarget.15005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362522PMC
February 2017

Application of In-line Focused Beam Reflectance Measurement to Brivanib Alaninate Wet Granulation Process to Enable Scale-up and Attribute-based Monitoring and Control Strategies.

J Pharm Sci 2017 01 19;106(1):224-233. Epub 2016 Oct 19.

Drug Product Science & Technology, Bristol-Myers Squibb Company, One Squibb Dr., New Brunswick, New Jersey 08903.

Application of in-line real-time process monitoring using a process analytical technology for granule size distribution can enable quality-by-design development of a drug product and enable attribute-based monitoring and control strategies. In this study, an in-line laser focused beam reflectance measurement (FBRM) C35 probe was used to investigate the effect of formulation and process parameters on the granule growth profile over time during the high shear wet granulation of a high drug load formulation of brivanib alaninate. The probe quantitatively captured changes in the granule chord length distribution (CLD) with the progress of granulation and delineated the impact of water concentration used during granulation. The results correlated well with offline particle size distribution measured by nested sieve analyses. An end point indication algorithm was developed that was able to successfully track the process time needed to reach the target CLD. Testing of the brivanib alaninate granulation through 25-fold scale-up of the batch process indicated that the FBRM CLD profile can provide a scale-independent granule attribute-based process fingerprint. These studies highlight the ability of FBRM to quantitate a granule attribute of interest during wet granulation that can be used as an attribute-based scale-up and process monitoring and control parameter.
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http://dx.doi.org/10.1016/j.xphs.2016.08.025DOI Listing
January 2017

Phage display library selection of a hypoxia-binding scFv antibody for liver cancer metabolic marker discovery.

Oncotarget 2016 Jun;7(25):38105-38121

Department of Medical Biochemistry and Cell Biology, School of Medicine, Nankai University, Tianjin, China.

Hypoxia, which is frequently observed in liver cancer and metastasis, influences tumor progression and resistance to therapy. Although hypoxia-associated biomarkers are of use in other cancers, none is recognized as a surrogate for hypoxia in liver cancer. In this study, we generated seven unique human single-chain Fv (scFv) antibodies (Abs) specific to hypoxic liver cancer cells, using normoxia-depleted vs hypoxia-selected phage library panning technology. By developing the scFv immunoprecipitation-based mass spectrometry method, the antigen that bound with one of the Abs (H103) was identified as the M2 splice isoform of pyruvate kinase (PKM2), an enzyme that is a key regulator of aerobic glycolysis in cancer cells. Increased expression of PKM2 was induced by hypoxia in liver cancer cell lines. Immunohistochemical (IHC) staining showed that PKM2 was highly expressed in moderately and well differentiated hepatocellular carcinoma (HCC) tissues with a hypovascular staining pattern. High expression of PKM2 was also localized in the perinecrotic area of intrahepatic cholangiocarcinoma (ICC) tissues. The percentage of the HCC or ICC tumor expressing PKM2 was significantly higher with more tumor necrosis, low microvessel density, and advanced stage. Moreover, the H103 scFv Ab was efficiently internalized into hypoxic liver cancer cells and could have potential for targeted drug delivery.

Conclusion: our study, for the first time, developed hypoxia-specific scFv Ab H103 to liver cancer cells, and revealed that PKM2 is a promising biomarker for hypoxia in HCC and ICC tissues. These allow further exploration of this valuable Ab and PKM2 antigen for hypoxia targeting in liver cancer.
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http://dx.doi.org/10.18632/oncotarget.9460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122375PMC
June 2016

Resolution and Sensitivity of Inline Focused Beam Reflectance Measurement During Wet Granulation in Pharmaceutically Relevant Particle Size Ranges.

J Pharm Sci 2016 12 13;105(12):3594-3602. Epub 2016 Oct 13.

Drug Product Science & Technology, Bristol-Myers Squibb Company, One Squibb Dr., New Brunswick, New Jersey 08903.

Real-time process monitoring using a process analytical technology for granule size distribution can enable quality-by-design in drug product manufacturing. In this study, the resolution and sensitivity of chord length distribution (CLD) measured inline inside a high shear granulator using focused beam reflectance measurement (FBRM) C35 probe was investigated using different particle size grades of microcrystalline cellulose (MCC). In addition, the impact of water and impeller tip speed on the measurement accuracy as well as correlation with offline particle sizing techniques (FBRM, laser diffraction [Malvern Mastersizer], microscopy [Sympatec QicPic], and nested sieve analysis) was studied. Inline FBRM resolved size differences between different MCC grades, and the data correlated well with offline analyses. Impeller tip speed changed the number density of inline CLD measurements while addition of water reduced the CLD of dry MCC, likely due to deagglomeration of primary particles. In summary, inline FBRM CLD measurement in high shear granulator provides adequate resolution and reproducible measurements in the pharmaceutically relevant size range both in the presence and in the absence of water. Therefore, inline FBRM can be a valuable tool for the monitoring of high shear wet granulation.
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http://dx.doi.org/10.1016/j.xphs.2016.09.001DOI Listing
December 2016

GRP75 upregulates clathrin-independent endocytosis through actin cytoskeleton reorganization mediated by the concurrent activation of Cdc42 and RhoA.

Exp Cell Res 2016 05 22;343(2):223-236. Epub 2016 Apr 22.

Department of Biochemistry & Cell Biology, School of Medicine, Nankai University, Tianjin, PR China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, PR China. Electronic address:

Therapeutic macromolecules are internalized into the cell by either clathrin-mediated endocytosis (CME) or clathrin-independent endocytosis (CIE). Although some chaperone proteins play an essential role in CME (e.g. Hsc70 in clathrin uncoating), relatively few of these proteins are functionally involved in CIE. We previously revealed a role for the mitochondrial chaperone protein GRP75 in heparan sulfate proteoglycan (HSPG)-mediated, membrane raft-associated macromolecule endocytosis. However, the mechanism underlying this process remains unclear. In this study, using a mitochondrial signal peptide-directed protein trafficking expression strategy, we demonstrate that wild-type GRP75 expression enhanced the uptakes of HSPG and CIE marker cholera toxin B subunit but impaired the uptake of CME marker transferrin. The endocytosis regulation function of GRP75 is largely mediated by its subcellular location in mitochondria and is essentially determined by its ATPase domain. Interestingly, the mitochondrial expression of GRP75 or its ATPase domain significantly stimulates increases in both RhoA and Cdc42 activation, remarkably induces stress fibers and enhances filopodia formation, which collectively results in the promotion of CIE, but the inhibition of CME. Furthermore, silencing of Cdc42 or RhoA impaired the ability of GRP75 overexpression to increase CIE. Therefore, these results suggest that endocytosis vesicle enrichment of GRP75 by mitochondria trafficking upregulates CIE through an actin cytoskeleton reorganization mechanism mediated by the concurrent activation of Cdc42 and RhoA. This finding provides novel insight into organelle-derived chaperone signaling and the regulation of different endocytosis pathways in cells.
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http://dx.doi.org/10.1016/j.yexcr.2016.04.009DOI Listing
May 2016

A fragment substitution in the promoter of CsHDZIV11/CsGL3 is responsible for fruit spine density in cucumber (Cucumis sativus L.).

Theor Appl Genet 2016 Jul 25;129(7):1289-1301. Epub 2016 Mar 25.

State Key Laboratory of Corp Biology, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Huanghuai Region), Ministry of Agriculture, College of Horticulture Science and Engineering, Shandong Agricultural University, No. 61 Daizong road, Tai'an, 271018, Shandong, China.

Key Message: The indel in the promoter of CsHDZIV11 co-segregates with fruit spine density and could be used for molecular breeding in cucumber. Fruit spine density is an important quality trait for marketing in cucumber (Cucumis sativus L.). However, the molecular basis of fruit spine density in cucumber remains unclear. In this study, we isolated a mutant, few spines 1 (fs1), from CNS2 (wild type, WT), a North China-type cucumber with a high density of fruit spines. Genetic analysis showed that fs1 was controlled by a single recessive Mendelian factor. Bulked segregant analysis combined with genome resequencing were used for mapping fs1 in the F2 population derived from a cross between the fs1 mutant and WT, and it was located on chromosome 6 through association analysis. To develop more polymorphic markers to locate fs1, another F2 population was constructed from the cross between fs1 and 'Chinese long' 9930. Then, fs1 was narrowed down to a 110.4-kb genomic region containing 25 annotated genes. A fragment substitution was identified in the promoter region of Csa6M514870 between fs1 and WT. This fragment in fs1 was also present in wild cucumber. Csa6M514870 encodes a PDF2-related protein, a homeodomain-leucine zipper IV transcription factor (CsHDZIV11/CsGL3) sharing high identity and similarity with proteins related to trichome formation or epidermal cell differentiation. Quantitative reverse-transcription PCR revealed a higher expression level of CsHDZIV11 in young fruits from fs1 compared to WT. A molecular marker based on this indel co-segregated with the spine density. This work provides a solid foundation not only for understanding the molecular mechanism of fruit spine density, but also for molecular breeding in cucumber.
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http://dx.doi.org/10.1007/s00122-016-2703-5DOI Listing
July 2016

De novo transcriptome sequencing of Agropyron cristatum to identify available gene resources for the enhancement of wheat.

Genomics 2015 Aug 15;106(2):129-36. Epub 2015 Apr 15.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Agropyron cristatum is a wild grass of the tribe Triticeae that is widely grown in harsh environments. As a wild relative of wheat, A. cristatum carries many resistance genes that could be used to broaden the genetic diversity of wheat. Here, we report the transcriptome sequencing of the flag leaf and young spike tissues of a representative tetraploid A. cristatum. More than 90 million reads from the two tissues were assembled into 73,664 unigenes. All unigenes were functionally annotated against the KEGG, COG, and Gene Ontology databases and predicted long non-coding RNAs. Pfam prediction demonstrates that A. cristatum carries an abundance of stress resistance genes. The extent of specific genes and rare alleles make A. cristatum a vital genetic reservoir for the improvement of wheat. Altogether, the available gene resources in A. cristatum facilitate efforts to harness the genetic diversity of wild relatives to enhance wheat.
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http://dx.doi.org/10.1016/j.ygeno.2015.04.003DOI Listing
August 2015
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