Publications by authors named "Yangyang Hu"

52 Publications

Comparison of the Effects of Different Testicular Sperm Extraction Methods on the Embryonic Development of Azoospermic Men in Intracytoplasmic Sperm Injection (ICSI) Cycles: A Retrospective Cohort Study.

Biomed Res Int 2021 17;2021:5515247. Epub 2021 May 17.

Reproductive Medical Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Background: The effects of different testicular sperm extraction methods on the embryonic development and clinical outcome of azoospermic men in intracytoplasmic sperm injection (ICSI) cycles have not been researched. Our goal was to evaluate the effect of different sperm retrieval methods used for patients with OA or NOA on the embryonic development and clinical outcomes during the ICSI cycles.

Methods: This was a retrospective cohort study. A total of 530 azoospermic patients who underwent 570 ICSI cycles met the study criteria. ICSI was performed using testicular sperm by TESA in 282 cycles (TESA group); ICSI with testicular sperm by mTESE was performed due to NOA in 90 cycles (mTESE group); ICSI with testicular sperm by MESA was performed in 198 cycles (MESA group). The embryonic development and clinical outcomes of the three groups were counted.

Results: The general characteristics of the three groups were comparable. Our findings showed that the three groups were matched in terms of infertility durations and age. The mean age and the mean BMI of the female partners were similar in the three groups. Also, our findings showed there were no significant differences in the three groups regarding day 3 of the menstrual cycle FSH and days of stimulation. The research results showed that the total dose of FSH and E2 on the HCG administration day was also not statistically different in the three groups. The number of oocytes retrieved had no significant differences in the three groups. However, the number of 2PNs per cycle and the number of cleavages per cycle were higher in the MESA group than in the other two groups; the TESA group and mTESE group were similar. The number of good quality D3 embryos and the number of good quality D5 embryos were significantly decreased in the mTESE group as compared to the other two groups. Good quality D3 embryos and the rate of good quality D5 embryos in the mTESE group were lower than those in the other two groups. Moreover, the clinical pregnancy rates of the TESA group (50.71%) and the MESA group (51.52%) were similar, but both were much higher than that of the mTESE group (32.22%).

Conclusions: The mTESE provides a good clinical outcome for NOA patients with severe spermatogenic impairment, including the rate of good quality D3 embryos, the rate of good quality D5 embryos, and the clinical pregnancy rate. However, our data suggested that both the TESA and MESA groups had better embryonic development and clinical outcomes than the mTESE group.
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http://dx.doi.org/10.1155/2021/5515247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149225PMC
May 2021

Two rice MYB transcription factors maintain male fertility in response to photoperiod by modulating sugar partitioning.

New Phytol 2021 May 25. Epub 2021 May 25.

Joint International Research Laboratory of Metabolic and Developmental Sciences, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Photoperiod-dependent male fertility is a critical enabler of modern hybrid breeding. A MYB transcription factor, CSA, is a key regulator of sugar partitioning in rice anthers, disruption of which causes photoperiod-sensitive male sterility. However, little is known about the molecular mechanisms governing plant fertility in response to photoperiod. Here, we have obtained another rice photoperiod-sensitive male sterile mutant, csa2, which exhibits semi-sterility under long-day (LD) conditions, with normal fertility under short-day (SD) conditions. CSA2 specifically expressed in anthers, and here is shown to be indispensable for sugar partitioning to anthers under LD conditions. The CSA2 protein can restore the fertility of csa mutants under SD conditions when expressed in a CSA-specific pattern, indicating that the two proteins share common downstream regulatory targets. Transcriptomic analyses also reveal discrete regulatory targets in anthers. Furthermore, the regulatory role of CSA2 in sugar transport was influenced by the photoperiod conditions during floral initiation, not simply during anther development. Collectively, we propose that rice evolved at least two MYB proteins, CSA2 and CSA, that regulate sugar transport in anthers under LD and SD conditions, respectively. This finding provides insight into the molecular mechanisms that regulate male fertility in response to photoperiod.
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http://dx.doi.org/10.1111/nph.17512DOI Listing
May 2021

Electronic Properties of Triangle Molybdenum Disulfide (MoS) Clusters with Different Sizes and Edges.

Molecules 2021 Feb 22;26(4). Epub 2021 Feb 22.

School of Physics, Harbin Institute of Technology, Harbin 150001, China.

The electronic structures and transition properties of three types of triangle MoS clusters, (Mo edge passivated with two S atoms), (Mo edge passivated with one S atom), and (S edge) have been explored using quantum chemistry methods. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap of B and C is larger than that of A, due to the absence of the dangling of edge S atoms. The frontier orbitals (FMOs) of A can be divided into two categories, edge states from S at the edge and hybrid states of Mo and S covering the whole cluster. Due to edge/corner states appearing in the FMOs of triangle MoS clusters, their absorption spectra show unique characteristics along with the edge structure and size.
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http://dx.doi.org/10.3390/molecules26041157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927058PMC
February 2021

Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair.

JCI Insight 2021 01 25;6(2). Epub 2021 Jan 25.

Department of Gastroenterology and.

Severe acute pancreatitis (AP) is a life-threatening disease with up to 30% mortality. Therefore, prevention of AP aggravation and promotion of pancreatic regeneration are critical during the course and treatment of AP. Hypertriglyceridemia (HTG) is an established aggravating factor for AP that hinders pancreatic regeneration; however, its exact mechanism remains unclear. Using miRNA sequencing and further verification, we found that miRNA-153 (miR-153) was upregulated in the pancreas of HTG animal models and in the plasma of patients with HTG-AP. Increased miR-153 aggravated HTG-AP and delayed pancreatic repair via targeting TRAF3. Furthermore, miR-153 was transcriptionally suppressed by sterol regulatory element-binding transcription factor 1c (SREBP1c), which was suppressed by lipoprotein lipase malfunction-induced HTG. Overexpressing SREBP1c suppressed miR-153 expression, alleviated the severity of AP, and facilitated tissue regeneration in vivo. Finally, therapeutic administration of insulin also protected against HTG-AP via upregulating SREBP1c. Collectively, our results not only provide evidence that HTG leads to the development of more severe AP and hinders pancreatic regeneration via inducing persistent dysregulation of SREBP1c/miR-153 signaling, but also demonstrate that SREBP1c activators, including insulin, might be used to treat HTG-AP in patients.
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http://dx.doi.org/10.1172/jci.insight.138584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934861PMC
January 2021

Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion.

Virol Sin 2020 Nov 9. Epub 2020 Nov 9.

State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC of 4.321 μmol/L and 2.910 μmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC of 2.349 μmol/L. These findings provide new ideas for screening and research related to HBV agents.
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http://dx.doi.org/10.1007/s12250-020-00306-2DOI Listing
November 2020

Effects of SLIRP on Sperm Motility and Oxidative Stress.

Biomed Res Int 2020 13;2020:9060356. Epub 2020 Oct 13.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.

Background: Deficient spermatozoon motility is one of the main causes of male infertility. However, there are still no accurate and effective treatments in a clinical setting for male asthenospermia. Exploring the genes and mechanism of asthenospermia has become one of the hot topics in reproductive medicine. Our aim is to study the effect of SLRIP on human spermatozoon motility and oxidative stress.

Methods: Sperm samples were collected including a normospermia group (60 cases) and an asthenospermia group (50 cases). SLIRP protein expression in spermatozoa was examined by western blotting, and relative mRNA expression of SLIRP in spermatozoa was quantified by reverse transcription polymerase chain reaction. Levels of reactive oxygen species (ROS), adenosine triphosphate (ATP) content, and the activity of manganese superoxide dismutase (MnSOD) in spermatozoa were also measured.

Results: The mRNA level and protein expression of SLIRP in the asthenospermia group were significantly reduced compared with those in the normospermia group. The ROS active oxygen level in the asthenospermia group significantly increased; however, the ATP content decreased significantly as well as the activity of MnSOD.

Conclusion: SLIRP regulates human male fertility, and SLIRP and sperm progressive motility are positively correlated. The expression of SLIRP is declined, oxidative damage is increased, and energy metabolism is decreased in spermatozoa of asthenospermia patients compared to normospermia participants.
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http://dx.doi.org/10.1155/2020/9060356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603556PMC
May 2021

Epigenetic repression of miR-17 contributed to di(2-ethylhexyl) phthalate-triggered insulin resistance by targeting Keap1-Nrf2/miR-200a axis in skeletal muscle.

Theranostics 2020 23;10(20):9230-9248. Epub 2020 Jul 23.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.

Skeletal muscle insulin resistance is detectable before type 2 diabetes is diagnosed. Exposure to di(2-ethylhexyl) phthalate (DEHP), a typical environmental endocrine-disrupting chemical, is a novel risk factor for insulin resistance and type 2 diabetes. This study aimed to explore insulin signaling regulatory pathway in skeletal muscle of the DEHP-induced insulin-resistant mice and to investigate potential therapeutic strategies for treating insulin resistance. C57BL/6J male mice were exposed to 2 mg/kg/day DEHP for 15 weeks. Whole-body glucose homeostasis, oxidative stress and deregulated miRNA-mediated molecular transduction in skeletal muscle were examined. microRNA (miRNA) interventions based on lentiviruses and adeno-associated viruses 9 (AAV9) were performed. Dnmt3a-dependent promoter methylation and lncRNA Malat1-related sponge functions cooperatively downregulated miR-17 in DEHP-exposed skeletal muscle cells. DEHP suppressed miR-17 to disrupt the Keap1-Nrf2 redox system and to activate oxidative stress-responsive Txnip in skeletal muscle. Oxidative stress upregulated miR-200a, which directly targets the 3'UTR of and , leading to hindered insulin signaling and impaired insulin-dependent glucose uptake in skeletal muscle, ultimately promoting the development of insulin resistance. AAV9-induced overexpression of miR-17 and lentivirus-mediated silencing of miR-200a in skeletal muscle ameliorated whole-body insulin resistance in DEHP-exposed mice. The miR-17/Keap1-Nrf2/miR-200a axis contributed to DEHP-induced insulin resistance. miR-17 is a positive regulator, whereas miR-200a is a negative regulator of insulin signaling in skeletal muscle, and both miRNAs have the potential to become therapeutic targets for preventing and treating insulin resistance or type 2 diabetes.
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http://dx.doi.org/10.7150/thno.45253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415800PMC
May 2021

A novel risk score based on a combined signature of 10 immune system genes to predict bladder cancer prognosis.

Int Immunopharmacol 2020 Oct 5;87:106851. Epub 2020 Aug 5.

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address:

Bladder cancer (BC) is a common internal malignant tumor with a poor prognosis worldwide. There is an urgent need to better understand the pathogenesis and progression of BC and to find useful biomarkers for diagnosis and prognosis. This study was aimed at developing a potential immunogenomic prognostic signature for BC patients. To identify possible immune-system-related genes (IRGs) whose parameters predict the survival of BC patients, we chose 371 BC patients and analyzed differentially expressed IRGs from The Cancer Genome Atlas (TCGA) datasets. We then derived a 10-IRG formula, including MMP9, RBP7, PDGFRA, AHNAK, OAS1, OLR1, RAC3, SLIT2, IGF1, and AGTR1, to estimate BC prognosis. To validate the mRNA levels of these IRGs, we performed quantitative PCR and found that the expression of these genes almost matched the corresponding mRNA expression levels in TCGA. Furthermore, we validated the prognostic value of the new risk model using two external datasets from Gene Expression Omnibus: GSE13507 (n = 165) and GSE32894 (n = 224). Our data pointed to a significant correlation between the risk model and patients' prognosis. Bioinformatic analysis revealed that products of the IRGs have possible effects on tumor immune processes such as an inflammatory response and cytokine-cytokine receptor interaction. Finally, assessment of the clinical value of the immune-system-based risk signature showed that several of these IRGs were differentially expressed between patients with different clinical characteristics: a high risk score positively correlated with female sex, advanced tumor stage, more advanced T stage, and lymph node metastasis. This immunogenomic signature may represents a reliable prognostic tool for BC and can help to design an individualized immunotherapy.
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http://dx.doi.org/10.1016/j.intimp.2020.106851DOI Listing
October 2020

Diagnostic, Therapeutic Predictive, and Prognostic Value of Neutrophil Extracellular Traps in Patients With Gastric Adenocarcinoma.

Front Oncol 2020 26;10:1036. Epub 2020 Jun 26.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Neutrophils are a significant population of infiltrated immune cells in the tumor microenvironment. Neutrophil extracellular traps (NETs) are implicated in the biological behavior of many malignant tumors. NETs can be degraded into soluble nucleosomes, leading to the release of fragments containing DNA and granule proteins into the peripheral blood (PB). Using human gastric cancer (GC) biopsies and PB samples, we investigated the specific value of NETs in GC from a clinical perspective. In summary, the formation of NETs was discovered in the tissue microenvironment and PB of GC patients. The amounts of NETs and neutrophil accumulation decreased from tumor tissue to paratumor tissue. In addition, the level of NETs in the PB gradually declined through the following patient populations: advanced disease patients, preoperative patients, postoperative patients, benign disease patients, and healthy controls. The levels of NETs in the plasma and serum were significantly correlated. As a serum biomarker, NETs had a better diagnostic value than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in GC. The neutrophil count and neutrophil to lymphocyte ratio (NLR) were significantly associated with the level of NETs in the PB. The existence of lymph node metastasis indicated a high level of NETs in the serum. Moreover, the level of NETs in the PB was inversely correlated with short-term efficacy in GC patients who had received advanced first-line treatment. The higher baseline level of NETs in the PB of patients with negative HER2 status was correlated with worse progression-free survival (PFS). And the level of NETs in the PB was a unfavorable independent prognostic factor for PFS in patients with advanced GC who had received first-line treatment. Thus, NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.
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http://dx.doi.org/10.3389/fonc.2020.01036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344202PMC
June 2020

Clinical features of rheumatic patients infected with COVID-19 in Wuhan, China.

Ann Rheum Dis 2020 08 22;79(8):1007-1013. Epub 2020 May 22.

Department of Rheumatology and Immunology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

Objective: The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice.

Methods: This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020.

Results: Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage.

Conclusions: Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered.

Trial Registration Number: ChiCTR2000030795.
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http://dx.doi.org/10.1136/annrheumdis-2020-217627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295865PMC
August 2020

RNA demethylase ALKBH5 prevents pancreatic cancer progression by posttranscriptional activation of PER1 in an m6A-YTHDF2-dependent manner.

Mol Cancer 2020 05 19;19(1):91. Epub 2020 May 19.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People's Republic of China.

Background: N6-methyladenosine (m6A) is the most abundant reversible methylation modification of eukaryotic mRNA, and it plays vital roles in tumourigenesis. This study aimed to explore the role of the m6A demethylase ALKBH5 in pancreatic cancer (PC).

Methods: The expression of ALKBH5 and its clinicopathological impact were evaluated in PC cohorts. The effects of ALKBH5 on the biological characteristics of PC cells were investigated on the basis of gain-of-function and loss-of-function analyses. Subcutaneous and orthotopic models further uncovered the role of ALKBH5 in tumour growth. mRNA and m6A sequencing and assays of m6A methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the targeted effect of ALKBH5 on PER1. P53-binding sites in the ALKBH5 promoter were investigated by ChIP and luciferase assays to reveal the interplay between ALKBH5 and PER1-activated ATM-CHK2-P53/CDC25C signalling.

Results: ALKBH5 loss characterized the occurrence and poor clinicopathological manifestations in patients with PC. Overexpression of ALKBH5 reduced tumoural proliferative, migrative, invasive activities in vitro and ameliorated tumour growth in vivo, whereas ALKBH5 knockdown facilitated PC progression. Mechanistically, ALKBH5 posttranscriptionally activated PER1 by m6A demethylation in an m6A-YTHDF2-dependent manner. PER1 upregulation led to the reactivation of ATM-CHK2-P53/CDC25C signalling, which inhibited cell growth. P53-induced activation of ALKBH5 transcription acted as a feedback loop regulating the m6A modifications in PC.

Conclusion: ALKBH5 serves as a PC suppressor by regulating the posttranscriptional activation of PER1 through m6A abolishment, which may highlight a demethylation-based approach for PC diagnosis and therapy.
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http://dx.doi.org/10.1186/s12943-020-01158-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236181PMC
May 2020

Evaluation of surface texture of dried Hami Jujube using optimized support vector machine based on visual features fusion.

Food Sci Biotechnol 2020 Apr 27;29(4):493-502. Epub 2019 Nov 27.

1College of Mechanical and Electrical Engineering, Shihezi University, Shihezi, 832003 Xinjiang China.

The surface texture of dried jujube fruits is a significant quality grading criterion. This paper introduced a novel visual feature fusion based on connected region density, texture features, and color features. The single-scale Two-Dimensional Discrete Wavelet Transform was used to perform single-scale decomposition and reconstruction of dried Hami jujube image before visual features extraction. The connected region density was extracted by the two different algorithms, whereas the texture features were extracted by Gray Level Co-occurrence Matrix and the color features were extracted by image processing algorithms. Based on selected features which obtained by correlation analysis of visual features, the accuracy rate of the optimized Support Vector Machine classification model was 96.67%. In comparing with Extreme Learning Machine classification model and other fusion methods, the optimized Support Vector Machine based on selected visual features fusion was better.
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http://dx.doi.org/10.1007/s10068-019-00683-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142174PMC
April 2020

Integrin β4-Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis.

Cancer Res 2020 02 16;80(4):771-783. Epub 2019 Dec 16.

Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.

Integrin β4 (ITGB4) has been shown to play an important role in the regulation of cancer stem cells (CSC). Immune targeting of ITGB4 represents a novel approach to target this cell population, with potential clinical benefit. We developed two immunologic strategies to target ITGB4: ITGB4 protein-pulsed dendritic cells (ITGB4-DC) for vaccination and adoptive transfer of anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)-armed tumor-draining lymph node T cells. Two immunocompetent mouse models were utilized to assess the efficacy of these immunotherapies in targeting both CSCs and bulk tumor populations: 4T1 mammary tumors and SCC7 head and neck squamous carcinoma cell line. Immunologic targeting of ITGB4 utilizing either ITGB4-DC or ITGB4 BiAb-T cells significantly inhibited local tumor growth and metastases in both the 4T1 and SCC7 tumor models. Furthermore, the efficacy of both of these ITGB4-targeted immunotherapies was significantly enhanced by the addition of anti-PD-L1. Both ITGB4-targeted immunotherapies induced endogenous T-cell cytotoxicity directed at CSCs as well as non-CSCs, which expressed ITGB4, and immune plasma-mediated killing of CSCs. As a result, ITGB4-targeted immunotherapy reduced not only the number of ITGB4 CSCs in residual 4T1 and SCC7 tumors but also their tumor-initiating capacity in secondary mouse implants. In addition, treated mice demonstrated no apparent toxicity. The specificity of these treatments was demonstrated by the lack of effects observed using ITGB4 knockout 4T1 or ITGB4-negative CT26 colon carcinoma cells. Because ITGB4 is expressed by CSCs across a variety of tumor types, these results support immunologic targeting of ITGB4 as a promising therapeutic strategy. This study identifies a novel mechanism of resistance to anti-PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-1145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024642PMC
February 2020

Effects of High Temperature and Drought Stress on the Expression of Gene Encoding Enzymes and the Activity of Key Enzymes Involved in Starch Biosynthesis in Wheat Grains.

Front Plant Sci 2019 12;10:1414. Epub 2019 Nov 12.

National Engineering Research Center for Wheat, College of Agriculture, Henan Agricultural University, Zhengzhou, Henan, China.

High temperature (HT) and drought stress (DS) play negative roles in wheat growth, and are two most important factors that limit grain yield. Starch, the main component of the wheat [][endosperm, accounts for 65-75% of grain weight, and is significantly influenced by environmental factors. To understand the effects of post-anthesis HT and DS on starch biosynthesis, we performed a pot experiment using wheat cultivar "Zhengmai 366" under field conditions combined with a climate-controlled greenhouse to simulate HT. There were two temperature regimes (optimum day/night temperatures of 25/15°C and high day/night temperatures of 32/22°C from 10 days after anthesis to maturity) accompanied by two water treatments (optimum of ∼75% relative soil water content, and a DS of ∼50% relative soil water content). Optimum temperature with optimum water treatment was the control (CK). We evaluated the expression patterns of 23 genes encoding six classes of enzymes involved in starch biosynthesis in wheat grains using real-time qPCR. HT, DS, and HT+DS treatments altered gene expression profiles. Compared to the CK, expression of 22 of the 23 genes was down regulated by HT, and only one gene () was up-regulated by HT. Actually was the only gene up-regulated by all three stress treatments. The expression of 17 genes was up-regulated, while six genes, including granule-bound starch synthase (), , and , were down-regulated by DS. Eleven genes were down-regulated and 12 were up-regulated by HT+DS. The activity of pyrophosphorylase, starch synthases starch branching enzymes in the stress treatments (HT, DS, and HT+DS) often appeared to peak values in advance and declined significantly to be lower than that in the CK. The genes that coordinated participation in the enzymes formation can serve as an indicator of the enzymes activity potentially involved in starch biosynthesis. HT, DS, and HT+DS altered the timing of starch biosynthesis and also influenced the accumulation of amylose, amylopectin, total starch, and sucrose. Under HT, DS, and HT+DS, the key enzymes activity and their genes expression associated with the conversion of sucrose to starch, was reduced, which was the leading cause of the reductions in starch content. Our study provide further evidence about the effects of stress on starch biosynthesis in wheat, as well as a physiological understanding of the impact of post-anthesis heat and DS on starch accumulation and wheat grain yield.
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http://dx.doi.org/10.3389/fpls.2019.01414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863091PMC
November 2019

Perfect Spin Filtering in Homobimetallic Ni Complex with High Tolerance to Structural Changes.

J Phys Chem Lett 2019 Dec 6;10(24):7842-7849. Epub 2019 Dec 6.

School of Physics , Harbin Institute of Technology , Harbin 150001 , China.

In the theory of ligand fields, depending on the nature and field strength of the surrounding ligands, the central metal ion may exhibit different electronic configurations, low spin (LS) or high spin (HS). Realizing stable spin polarization is one of the main challenges in the field of molecular spintronic devices because of spin switching triggered by an external stimulus. Here, an asymmetric homobimetallic complex has been investigated using the nonequilibrium Green's function and spin density functional theory. Our calculations indicate that the homobimetallic complex can achieve negative differential resistance, rectification effect, and perfect spin filtering transport on the level of an individual molecule. Strikingly, when the molecule is stretched by 0.45 Å, the HS state is still the most stable because of the weak magnetic Ni-Ni interaction. Although its conductivity decreases by 30%, the efficiency of spin filtering remains 100%. These obtained theoretical findings suggest that the homobimetallic complexes hold great potential in molecular spintronics.
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http://dx.doi.org/10.1021/acs.jpclett.9b02954DOI Listing
December 2019

Major capsid protein of Autographa californica multiple nucleopolyhedrovirus contributes to the promoter activity of the very late viral genes.

Virus Res 2019 11 18;273:197758. Epub 2019 Sep 18.

State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. Electronic address:

The baculovirus expression vector system (BEVS) is one of the most powerful eukaryotic expression systems. Recombinant protein expression is usually controlled by promoters of the baculovirus very late genes (i.e., polyhedrin and p10); therefore, identifying novel regulatory factors for these promoters is key to increasing BEVS productivity. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the viral vector most frequently used in BEVS. VP39 is the major nucleocapsid protein of AcMNPV and plays a pivotal role in nucleocapsid assembly in the nucleus. In this study, we found that knocking out vp39 from the AcMNPV genome resulted in decreased protein abundance of polyhedrin and P10. Further assays revealed that the mRNA transcripts and the promoter activities of polyhedrin and p10 were decreased in the absence of vp39, suggesting that VP39 contributes to the activity of the very late viral gene promoters and may represent a means of optimizing the current BEVS.
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http://dx.doi.org/10.1016/j.virusres.2019.197758DOI Listing
November 2019

Transport and Photoelectric Properties of 2D Silicene/MX (M = Mo, W; X = S, Se) Heterostructures.

ACS Omega 2018 Oct 16;3(10):13251-13262. Epub 2018 Oct 16.

Department of Physics, Harbin Institute of Technology, Harbin 150001, China.

The transport and photoelectric properties of four two-dimensional (2D) silicene/MX (M = Mo, W; X = S, Se) heterostructures have been investigated by employing density functional theory, nonequilibrium Green's function, and Keldysh nonequilibrium Green's function methods. The stabilities of silicene (SiE) are obviously improved after being placed on the MX (M = Mo, W; X = S, Se) substrates. In particular, the conductivities of SiE/MX are enhanced compared with free-standing SiE and MX. Moreover, the conductivities are increased with the group number of X, i.e., in the order of SiE < SiE/MS < SiE/MSe. An evident current oscillation phenomenon is observed in the SiE/WX heterostructures. When a linear light illumination is applied, SiE/MSe shows a stronger photoresponse than SiE/MS. The maximum photoresponse with a value of 9.0/photon was obtained for SiE/WSe. More importantly, SiE/MS (M = Mo, W) heterostructures are good candidates for application in designing solar cells owing to the well spatial separation of the charge carriers. This work provides some clues for further exploring 2D SiE/MX heterostructures involving tailored photoelectric properties.
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http://dx.doi.org/10.1021/acsomega.8b01282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644475PMC
October 2018

Structural and functional abnormalities of penile cavernous endothelial cells result in erectile dysfunction at experimental autoimmune prostatitis rat.

J Inflamm (Lond) 2019 25;16:20. Epub 2019 Jul 25.

Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, NO 301 Yanchang Road, Shanghai, 200072 People's Republic of China.

Background: There is growing recognition of the association of CP/CPPS accompany with ED. However, the specific mechanism of action remains unclear. The aim of this study was to investigate structural and functional abnormalities of cavernous endothelial cells in EAP rat, which may result in the ED.

Methods: we use rat prostate protein extract supplemented with immunoadjuvant to induce EAP rat, ICP and MAP were measured and inflammatory factor infiltration, Akt, eNOS, AR, nNOS and iNOS in the corpus cavernosum were tested. Subsequently, the normal rat and EAP rat cavernosum endothelial cells were purified by MACS, and the metabolism, oxidative stress, MMP, Akt, eNOS, AR and iNOS were evaluated.

Results: The EAP rat model was successfully constructed. The ratio of max ICP/MAP in EAP rat was significantly lower and TNF-α infiltration in corpus cavernosum was significantly higher than normal rats. Besides, Akt, eNOS and AR were decreased, iNOS was significantly increased. The growth and metabolism of endothelial cells in the EAP rats corpus cavernosum decreased and inflammatory factor mRNA was increased and intracellular oxidative stress was also increased significantly. The MMP of EAP rats cavernosum endothelial cells decreased and the expression of Akt, eNOS and AR were also significantly decreased, iNOS was significantly increased.

Conclusion: The prostate suffer local inflammatory infiltrate and promotes cytokines infiltrated into corpus cavernosum caused the oxidative stress increases and the metabolism or MMP decreases. In addition, AR, Akt and eNOS expression and phosphorylation are also reduced, thereby inhibiting the diastolic function of the corpus cavernosum, resulting in decreased erectile function.
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http://dx.doi.org/10.1186/s12950-019-0224-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659287PMC
July 2019

Porous [email protected] nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model.

Int J Nanomedicine 2019 24;14:3845-3860. Epub 2019 May 24.

Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, People's Republic of China.

 Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous [email protected] nanocomposite on bone regeneration and the underlying biological mechanisms.  We oxidized Se to develop Se quantum dots, then we used the Se quantum dots to form a solid [email protected] nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous [email protected] nanocomposite. We used XRD pattern to assess the phase structure of the solid [email protected] nanocomposite. The morphology of porous [email protected] nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous [email protected] nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous [email protected] nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous [email protected] nanocomposite.  In vitro, intervention with porous [email protected] nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against HO-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous [email protected] nanocomposite accelerated bone fracture healing using a rat femur fracture model.  Porous [email protected] nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous [email protected] nanocomposite may provide clinic benefit for bone tissue engineering.
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http://dx.doi.org/10.2147/IJN.S202741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539174PMC
August 2019

Restoration of p53 acetylation by HDAC inhibition permits the necrosis/apoptosis switch of pancreatic ainar cell during experimental pancreatitis in mice.

J Cell Physiol 2019 12 6;234(12):21988-21998. Epub 2019 May 6.

Shanghai Key Laboratory of Pancreatic Disease, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

The severity of acute pancreatitis (AP) is greatly attributed to the pancreatic acinar cell (PAC) death response. It has been established that the apoptosis-inducing therapy can protect against experimental pancreatitis and have great clinical therapeutic potential. However, current pharmacologic agents that target apoptosis during AP largely lack specificity. Thus, it remains imperative to reveal the specific mechanisms governing acinar cell death. Death responses of PAC are manifested by the progressive necrosis accompanied by apoptosis silencing during AP in mice. In this study, we found that the transcriptional activity of p53 was impaired and the expressions of its proapoptotic targets Puma and CD95 were significantly decreased, which explains the apoptosis silencing during AP. Furthermore, we found that the functional depression of p53 was resulted from histone deacetylase (HDAC)-mediated deacetylation of p53 C-terminal in PAC during AP. Treatment of the HDAC inhibitor trichostatin-A restored p53 apoptosis pathway, resulted in a necrosis/apoptosis switch and protected mice from cerulein- or l-Arg-induced AP. Our research identified the HDAC-dependent regulation of p53 activity as a critical mechanism underlying acinar cell death response, which represents a specific target for the treatment of AP.
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http://dx.doi.org/10.1002/jcp.28761DOI Listing
December 2019

Corrigendum to 'Conserved signaling pathways underlying heterotopic ossification' [Bone, 109, April 2018, 43-48].

Bone 2019 May 28;122:254. Epub 2019 Feb 28.

School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Department of Medical Laboratory Science, Bengbu Medical College, Bengbu 233030, China; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bone.2019.02.023DOI Listing
May 2019

Development and Application of Immunoaffinity Column Purification and Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry for Determination of Domoic Acid in Shellfish.

Toxins (Basel) 2019 02 1;11(2). Epub 2019 Feb 1.

Jiangsu Meizheng Biotechnology Company Limited, Wuxi 214135, Jiangsu, China.

Domoic acid (DA) is a neurotoxin associated with amnesic shellfish poisoning (ASP). Though LC coupled to tandem mass spectrometry (LC-MS/MS) has become the preferred method for DA determination, traditional sample pretreatment is still labor-intensive. In this study, a simple, efficient and selective method for LC-MS/MS analysis of DA in shellfish was established by optimizing clean-up procedures on a self-assembly immunoaffinity column (IAC). Shellfish was extracted with 75% methanol twice and diluted with phosphate buffered saline (PBS, 1:2). The mixture was purified on IAC as follows: preconditioned with PBS, loaded with sample, washed by 50% MeOH, and eluted with MeOH containing 2% ammonium hydroxide. Concentrated analyte was monitored by multiple reaction monitoring (MRM) using electrospray (ESI) positive ion mode throughout the LC gradient elution. Based on the post-extraction addition method, matrix effects for various shellfish matrices were found to be less than 8%. The developed method was fully validated by choosing mussel as the representative matrix. The method had a limit of detection (LOD) of 0.02 µg·g, showed excellent linear correlation in the range of 0.05⁻40 µg·g, and obtained ideal recoveries (91⁻94%), intra-day RSDs (6⁻8%) and inter-day RSDs (3⁻6%). The method was successfully applied to DA determination in 59 shellfish samples, with a detection rate of 10% and contaminated content of 0.1⁻14.9 µg·g.
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http://dx.doi.org/10.3390/toxins11020083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409838PMC
February 2019

[Anti-inflammatory effect of interleukin-35 in mice with colitis and its mechanism].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2018 May;47(5):499-506

Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.

Objective: To investigate the anti-inflammatory effect and mechanisms of interleukin-35 (IL-35) in inflammatory bowel disease.

Methods: BALB/c mice were divided into three groups with 10 mice in each group:control group, model group (oral administration of 4% glucan sodium sulfate for 7 d) and IL-35-treated group (oral administration of 4% glucan sodium sulfate for 7 d, intraperitoneal injection of 2 μg IL-35 at d2-5). Disease activity index (DAI) was scored every day. After 7 d, the mice were sacrificed, and the serum and intestinal tissue samples were collected. The gross morphology of the colon was observed; HE staining was used to observe the pathological changes of colon tissue; flow cytometry was employed to detect the change of macrophage polarization ratio in colon tissue; the mRNA expression levels of cytokines IL-6, TNF-α, IFN-γ, IL-10 and SHIP1 in colon tissue were determined by real-time quantitative RT-PCR; the expression and distribution of SHIP1 in colon tissue was measured by immunohistochemistry; Western blotting was adopted to detect the expression level of SHIP1 protein in colonic intestinal tissues of each group.

Results: The DAI scores of the mice in the model group were higher than those in the control group, while the DAI scores in the IL-35-treated group were lower than those in the model group (all <0.01). Compared with the control group, the colon length was significantly shortened in the model group (<0.05), while the colon length of the IL-35-treated group had an increasing trend compared with the model group, but the difference was not statistically significant (>0.05). Compared with the model group, microscopic inflammatory infiltration score was decreased and microscopic crypt destruction and score was significantly lower in IL-35-treated group (all <0.05). The relative expression of proinflammatory cytokines IL-6, TNF-α and IFN-γ in the colon tissue of IL-35-treated group was decreased compared with the model group, while the relative expression of IL-10 mRNA was higher than that of the model group (all <0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased (<0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group (<0.05). The relative expression of SHIP1 mRNA and protein in the colon tissue of IL-35-treated group was higher than that in the model group (all <0.05).

Conclusions: IL-35 can inhibit the polarization of M1 macrophages and regulate inflammatory cytokines to promote anti-inflammatory effect on mice with colitis.
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May 2018

LncRNA MALAT1 promotes relapse of breast cancer patients with postoperative fever.

Am J Transl Res 2018 15;10(10):3186-3197. Epub 2018 Oct 15.

Department of Breast Surgery, The Third Hospital of Nanchang City Nanchang 330009, Jiangxi, People's Republic of China.

Postoperative fever is prevalent in many breast cancer patients. Some retrospective studies proposed that postoperative fever might also be considered as a rapid rough indicator for the poor prognosis of breast cancer patients. This study aims to explore the possible molecular mechanisms underlying the relapse of breast cancer patients with early postoperative fever. Our results indicated plasma levels of lncRNA MALAT1 were elevated in breast cancer patients with early postoperative fever and were associated with RFS. Lipopolysaccharide (LPS) was able to induce fever and systemic inflammatory responses in 4T1 xenograft mice, and promote lung metastasis. But after knocking down lncRNA MALAT1, the inflammatory responses and metastasis of lung were significantly reduced. Moreover, after knocking down lncRNA MALAT1 in the 4T1 cells, TNF-α level in the supernatants was sharply decreased, and the invasion and migration induced by LPS was also weakened. Cumulatively, our data indicates that MALAT1 is closely related to recurrence and metastasis of breast cancer patients with early postoperative fever.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220217PMC
October 2018

New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis.

Redox Biol 2019 01 19;20:247-260. Epub 2018 Oct 19.

The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province 646000, China. Electronic address:

Oxidative stress and inflammation interact in the development of diabetic atherosclerosis. Intracellular hyperglycemia promotes production of mitochondrial reactive oxygen species (ROS), increased formation of intracellular advanced glycation end-products, activation of protein kinase C, and increased polyol pathway flux. ROS directly increase the expression of inflammatory and adhesion factors, formation of oxidized-low density lipoprotein, and insulin resistance. They activate the ubiquitin pathway, inhibit the activation of AMP-protein kinase and adiponectin, decrease endothelial nitric oxide synthase activity, all of which accelerate atherosclerosis. Changes in the composition of the gut microbiota and changes in microRNA expression that influence the regulation of target genes that occur in diabetes interact with increased ROS and inflammation to promote atherosclerosis. This review highlights the consequences of the sustained increase of ROS production and inflammation that influence the acceleration of atherosclerosis by diabetes. The potential contributions of changes in the gut microbiota and microRNA expression are discussed.
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http://dx.doi.org/10.1016/j.redox.2018.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205410PMC
January 2019

A computational study on a multimode spin conductance switching by coordination isomerization in organometallic single-molecule junctions.

Phys Chem Chem Phys 2018 Aug;20(30):20280-20286

School of Materials Science and Engineering, Harbin University of Science and Technology, Harbin 150080, China.

Single-molecule junctions provide the additional flexibility of tuning the on/off conductance states through molecular design. Here, we focus on a family of organometallic complexes with a conjugated curved buckybowl as the ligand. Using first-principles calculations, a multi-mode reversible spin switching based on the CpFe·corannulene complex is predicted by the temperature control of the CpFe+ coordination position in corannulene. The different spin conductance states for three coordinated modes are ascribed to the different electronic spin states of the organometallic complex due to crystal field effects. The predicted relative stabilities of isomers and the energy barriers of isomerization reactions can ensure that the conversion among the three isomers can occur quickly and, at a specific temperature, a dominant isomer has a higher proportion than the other two isomers. This provides a new framework for understanding transport in organometallic complexes with localized d states. This presents an exciting opportunity for exploiting junctions involving molecular spin switching.
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http://dx.doi.org/10.1039/c8cp02914hDOI Listing
August 2018

Erratum: Protective effect of asiatic acid in an experimental cerulein-induced model of acute pancreatitis in mice.

Am J Transl Res 2018 15;10(6):1930-1934. Epub 2018 Jun 15.

Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University 301 Yanchang Road, Jingan District, Shanghai 200072, People's Republic of China.

[This corrects the article on p. 3842 in vol. 9, PMID: 28861174.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038078PMC
June 2018

Double-helix PLi chains: novel potential nonlinear optical materials.

Phys Chem Chem Phys 2018 May;20(18):12618-12623

Key Laboratory of Green Chemical Technology of College of Heilongjiang Province, College of Chemical and Environmental Engineering, Harbin University of Science and Technology, Harbin 150080, China.

The structures, circular dichroism (CD) spectra and nonlinear optical (NLO) responses of a series of inorganic double-helix chains, PnLin (n = 6-12), have been investigated using the quantum chemistry method. P-P and P-Li interactions play a major role in stabilizing double-helix chains. The distinctive CD spectra of the double-helix frameworks (namely, a sharp negative CD band at short-wavelength region and a positive CD band at long-wavelength region) become obvious with increasing number of PLi units. The NLO response augments with the length of the double-helix chains, and the contribution of the axial component along the chain direction gradually becomes crucial simultaneously. Synergistic effects, a decrease of crucial electronic transition energies and charge transfer excitation give rise to enhanced NLO responses. In particular, the electronic transitions from the highest occupied molecular orbital to the lowest unoccupied molecular orbital make significant contributions not only to the positive CD bands in the long-wavelength region, but also to the NLO responses of the double-helix PnLin (n = 6-12) chains.
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http://dx.doi.org/10.1039/c8cp01116hDOI Listing
May 2018

Ac102 Participates in Nuclear Actin Polymerization by Modulating BV/ODV-C42 Ubiquitination during Autographa californica Multiple Nucleopolyhedrovirus Infection.

J Virol 2018 06 29;92(12). Epub 2018 May 29.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China

As a virus-encoded actin nucleation promoting factor (NPF), P78/83 induces actin polymerization to assist in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) propagation. According to our previous study, although P78/83 actively undergoes ubiquitin-independent proteasomal degradation, AcMNPV encodes budded virus/occlusion derived virus (BV/ODV)-C42 (C42), which allows P78/83 to function as a stable NPF by inhibiting its degradation during viral infection. However, whether there are other viral proteins involved in regulating P78/83-induced actin polymerization has yet to be determined. In this study, we found that Ac102, an essential viral gene product previously reported to play a key role in mediating the nuclear accumulation of actin during AcMNPV infection, is a novel regulator of P78/83-induced actin polymerization. By characterizing an knockout bacmid, we demonstrated that Ac102 participates in regulating nuclear actin polymerization as well as the morphogenesis and distribution of capsid structures in the nucleus. These regulatory effects are heavily dependent on an interaction between Ac102 and C42. Further investigation revealed that Ac102 binds to C42 to suppress K48-linked ubiquitination of C42, which decreases C42 proteasomal degradation and consequently allows P78/83 to function as a stable NPF to induce actin polymerization. Thus, Ac102 and C42 form a regulatory cascade to control viral NPF activity, representing a sophisticated mechanism for AcMNPV to orchestrate actin polymerization in both a ubiquitin-dependent and ubiquitin-independent manner. Actin is one of the most functionally important proteins in eukaryotic cells. Morphologically, actin can be found in two forms: a monomeric form called globular actin (G-actin) and a polymeric form called filamentous actin (F-actin). G-actin can polymerize to form F-actin, and nucleation promoting factor (NPF) is the initiator of this process. Many viral pathogens harness the host actin polymerization machinery to assist in virus propagation. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) induces actin polymerization in host cells. P78/83, a viral NPF, is responsible for this process. Previously, we identified that BV/ODV-C42 (C42) binds to P78/83 and protects it from degradation. In this report, we determined that another viral protein, Ac102, is involved in modulating C42 ubiquitination and, consequently, ensures P78/83 activity as an NPF to initiate actin polymerization. This regulatory cascade represents a novel mechanism by which a virus can harness the cellular actin cytoskeleton to assist in viral propagation.
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http://dx.doi.org/10.1128/JVI.00005-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974488PMC
June 2018

The MiR-135b-BMAL1-YY1 loop disturbs pancreatic clockwork to promote tumourigenesis and chemoresistance.

Cell Death Dis 2018 02 2;9(2):149. Epub 2018 Feb 2.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Circadian disruption has been implicated in tumour development, but the underlying mechanism remains unclear. Here, we show that the molecular clockwork within malignant human pancreatic epithelium is disrupted and that this disruption is mediated by miR-135b-induced BMAL1 repression. miR-135b directly targets the BMAL1 3'-UTR and thereby disturbs the pancreatic oscillator, and the downregulation of miR-135b is essential for the realignment of the cellular clock. Asynchrony between miR-135b and BMAL1 expression impairs the local circadian gating control of tumour suppression and significantly promotes tumourigenesis and resistance to gemcitabine in pancreatic cancer (PC) cells, as demonstrated by bioinformatics analyses of public PC data sets and in vitro and in vivo functional studies. Moreover, we found that YY1 transcriptionally activated miR-135b and formed a 'miR-135b-BMAL1-YY1' loop, which holds significant predictive and prognostic value for patients with PC. Thus, our work has identified a novel signalling loop that mediates pancreatic clock disruption as an important mechanism of PC progression and chemoresistance.
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http://dx.doi.org/10.1038/s41419-017-0233-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833454PMC
February 2018