Publications by authors named "Bo Huang"

1,102 Publications

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Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway.

Oxid Med Cell Longev 2021 5;2021:8542809. Epub 2021 Oct 5.

Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, China.

Patients with metabolic syndrome have a higher risk of type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance is the common pathophysiological basis of metabolic syndrome. The higher incidence of insulin resistance in obese groups is due to increased levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for insulin resistance has great significance for the treatment of the metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, antitumor, and improving insulin sensitivity. However, the target of DHM and molecular mechanism of DHM for preventing inflammation-induced insulin resistance is still unclear. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance by activating Ca-CaMKK-AMPK using signal pathway blockers, Ca probes, and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca-CaMKK-AMPK signaling pathway by interacting with the phospholipase C (PLC), its target protein, using drug affinity responsive target stability (DARTS) assay. Our results not only demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing PLC.
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http://dx.doi.org/10.1155/2021/8542809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510796PMC
October 2021

Anisotropic Mechanical Response and Strain Localization of a Metallic Glassy-Fiber-Reinforced Polyethylene Terephthalate Fabric.

Materials (Basel) 2021 Sep 27;14(19). Epub 2021 Sep 27.

Laboratory for Microstructures, Institute of Materials, Shanghai University, Shanghai 200444, China.

Optimizing the mechanical properties of composites through microstructural design has been a long-standing issue in materials science. In this study, we reinforced a typical polymer, i.e., polyethylene-terephthalate-woven fabric, with a type of Fe-based metallic glassy fiber (MGF) with an extremely large Young's moduli. The MGF-reinforced fabrics, with three different fiber bundle orientations (0°, 45°, and 90°), were investigated by in situ electron-microscopy mechanical testing techniques in conjunction with a digital image correlation (DIC) technique. The fabrics exhibited a pronounced anisotropic mechanical response, and the associated characteristics were verified to depend on the fiber bundle orientation relative to the external load. Furthermore, localized strains near the intersections of the fiber bundles were found to be much higher than the global strain. It is confirmed that the restriction from warp to weft is the dominant factor influencing strain localization during deformation. Our results are enlightening for understanding the fracture mechanisms of composites.
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http://dx.doi.org/10.3390/ma14195619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509627PMC
September 2021

Association between functional genetic variants in retinoid X receptor-α/γ and gestational diabetes mellitus risk in a southern Chinese population.

Biosci Rep 2021 Oct 11. Epub 2021 Oct 11.

Fujian Provincial Maternity and Children's Hospital, Fuzhou, China.

To clarify the effect of retinoid X receptor-a/g (RXR-α/γ) genes functional genetic variants (RXR-α rs4842194 G>A, RXR-γ rs100537 A>G and rs2134095 T>C) on the risk of gestational diabetes mellitus (GDM), a case-control study with 573 GDM patients and 740 pregnant women with normal glucose tolerance was performed in Guangxi area of China. An odds ratio (OR) with its corresponding 95%CI was used to assess the strengths of the association between genetic variation and GDM. After adjustment of age and pre-BMI, the logistic regression analysis showed that the rs2134095 was significantly associated with GDM risk (CC vs. TT/TC: adjusted OR=0.71, 95%CI=0.56~0.90) in all subjects, and this result remained highly significant after Bonferroni's correction for multiple testing (P=0.004). The stratified analysis showed that rs2134095 was significantly associated with the risk of GDM among age>30 years (adjusted OR=0.61, 95%CI=0.39~0.97), BMI>22 kg/m2 (adjusted OR=0.46, 95%CI= 0.30~0.70), SBP>120mmHg (adjusted OR=1.96, 95%CI= 1.14~3.36), HbA1c<6.5%(adjusted OR=1.41, 95%CI=1.11~1.78), TG≤1.7mmol/L(adjusted OR=2.57,95%CI=1.45~4.53), TC≤ 5.18mmol/L (adjusted OR=1.58, 95%CI=1.13~2.22), HDL-c≤1.5mmol/L(adjusted OR=1.70, 95%CI= 1.16~2.49) and LDL-c> 3.12 mmol/L(adjusted OR= 1.47, 95%CI= 1.08~2.00) subjects, under the recessive genetic model. We also found that rs2134095 interacted with age (Pinteraction=0.039), pre-BMI (Pinteraction=0.040) and TG (Pinteraction=0.025) influencing individual's genetic susceptibility to GDM. The rs2134095 T>C is significantly associated with the risk of GDM by effect of a single locus and / or complex joint gene-gene and gene-environment interactions. Larger sample-size and different population studies are required to confirm the findings.
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http://dx.doi.org/10.1042/BSR20211338DOI Listing
October 2021

Combined effects of chronic PM2.5 exposure and habitual exercise on cancer mortality: a longitudinal cohort study.

Int J Epidemiol 2021 Oct 11. Epub 2021 Oct 11.

Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.

Background: Exercise may increase the inhalation and deposition of air pollutants, which may counteract its beneficial effects. We thus examined the combined effects of chronic exposure to fine particulate matter (PM2.5) and habitual exercise on the risk of death from cancer in Taiwan.

Patients And Methods: A total of 384 128 adults (≥18 years of age) were recruited for a medical screening programme between 2001 and 2016, yielding 842 384 medical-examination records. All participants were followed up until 31 May 2019. Vital data were obtained from the National Death Registry of Taiwan and the ambient PM2.5 exposure was estimated using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. The time-dependent Cox-regression model was used to evaluate the combined effects.

Results: A greater amount of habitual exercise was associated with lower risk of death from cancer, whilst a higher level of PM2.5 exposure was associated with a higher risk of death from cancer. The inverse associations of habitual exercise with death from cancer were not modified by chronic exposure to PM2.5. The participants in the group with a high level of exercise and a low level of PM2.5 exposure exhibited a 35% lower risk of death from cancer than those in the group with a low level of exercise and a high level of PM2.5 exposure (95% confidence interval: 28%, 42%).

Conclusions: Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower risk of death from cancer. Habitual exercise reduces the risk of death from cancer regardless of the levels of chronic PM2.5 exposure. Our results indicate that habitual exercise is a suitable health-promotion strategy even for people who reside in moderately polluted regions.
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http://dx.doi.org/10.1093/ije/dyab209DOI Listing
October 2021

Rab1A promotes IL-4R/JAK1/STAT6-dependent metastasis and determines JAK1 inhibitor sensitivity in non-small cell lung cancer.

Cancer Lett 2021 Oct 8;523:182-194. Epub 2021 Oct 8.

Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201900, China. Electronic address:

Rab1A overexpression has been observed in several cancer types, however, its significance and the underlying mechanisms in non-small cell lung cancer (NSCLC) remain largely unexplored. This study demonstrated that Rab1A overexpression in NSCLC was significantly correlated to short survival and metastasis. Rab1A overexpression promoted cancer cell migration, invasion, and metastasis both in vitro and in vivo, by activating JAK1/STAT6 signaling through stabilizing IL-4Rα protein. Strikingly, high Rab1A level was associated with sensitivity to JAK1 inhibitor, and Rab1A overexpression rendered cancer cells vulnerable to JAK1-targeted agents. JAK1 inhibitor, Itacitinib adipate, dramatically inhibited high Rab1A NSCLC metastasis, in both cell line and patient derived xenograft models. Collectively, these findings demonstrated that Rab1A plays a critical role in the aggressive properties of NSCLC, revealing a unique mechanism by which it promotes metastasis. In addition, we found that Rab1A is a determinant of JAK1 inhibitor sensitivity, which could be explored for improving JAK1-targeted cancer therapy.
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http://dx.doi.org/10.1016/j.canlet.2021.10.008DOI Listing
October 2021

Nanophotonic inverse design with deep neural networks based on knowledge transfer using imbalanced datasets.

Opt Express 2021 Aug;29(18):28406-28415

Deep neural networks (DNNs) have been used as a new method for nanophotonic inverse design. However, DNNs need a huge dataset to train if we need to select materials from the material library for the inverse design. This puts the DNN method into a dilemma of poor performance with a small training dataset or loss of the advantage of short design time, for collecting a large amount of data is time consuming. In this work, we propose a multi-scenario training method for the DNN model using imbalanced datasets. The imbalanced datasets used by our method is nearly four times smaller compared with other training methods. We believe that as the material library increases, the advantages of the imbalanced datasets will become more obvious. Using the high-precision predictive DNN model obtained by this new method, different multilayer nanoparticles and multilayer nanofilms have been designed with a hybrid optimization algorithm combining genetic algorithm and gradient descent optimization algorithm. The advantage of our method is that it can freely select discrete materials from the material library and simultaneously find the inverse design of discrete material type and continuous structural parameters of the nanophotonic devices.
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http://dx.doi.org/10.1364/OE.435427DOI Listing
August 2021

EXPRESS: Object-based Encoding in Visual Working Memory: A Critical Revisit.

Q J Exp Psychol (Hove) 2021 Oct 5:17470218211052502. Epub 2021 Oct 5.

Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, P.R. China 12377.

Visual working memory (VWM) is responsible for the temporal retention and manipulation of visual information. It has been suggested that VWM employs an object-based encoding (OBE) manner to extract highly-discriminable information from visual perception: Whenever one feature dimension of the objects is selected for entry into VWM, the other task-irrelevant highly-discriminable dimension is also extracted into VWM involuntarily. However, the task-irrelevant feature in OBE studies might reflect a high capacity fragile VWM trace (FVWM for short) that stores maskable sensory representations. To directly compare the VWM storage hypothesis and the FVWM storage hypothesis, we used a unique characteristic of FVWM that the representations in FVWM could be erased by backward masks presented at the original locations of the memory array. We required participants to memorize the orientations of three colored bars while ignoring their colors, and presented backward masks during the VWM maintenance interval. In four experiments, we consistently observed that the OBE occurs regardless of the presentation of the backward masks, except when even the task-relevant features in VWM were significantly interrupted by immediate backward masks, suggesting that the task-irrelevant features of objects are stored in VWM rather than in FVWM.
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http://dx.doi.org/10.1177/17470218211052502DOI Listing
October 2021

Epidemiology of Sports-Related Eye Injuries Among Athletes in Tianjin, China.

Front Med (Lausanne) 2021 16;8:690528. Epub 2021 Sep 16.

Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.

To investigate the incidence, characteristics, and risk factors of sports-related eye injuries among athletes in Tianjin, China. A cross-sectional study was carried out from March 2018 to October 2018. In this study, the athletes from Tianjin University of Sports, Tianjin Vocational College of Sports, and Tianjin provincial sports teams were selected for general investigation. In total, 1,673 athletes were invited and 1,413 participated in the study (response rate of 84.5%). In total, 1,413 athletes were enrolled; 151 had suffered from sports-related eye injuries, with an incidence of 10.7% (95% : 9.1-12.0%). Handball (38.5%) was the sport with the highest incidence of eye injuries, followed by water polo (36.4%) and diving (26.7%). Overall, 42.4% of the athletes were injured by ball and 22.5% of injuries came from teammates. The eye injuries usually occurred during training (64.2%) and competitions (14.6%). Adnexa wound (51.7%) was the most common type of injury. About 11.9% of the athletes with eye injuries had the impaired vision; 66.7% failed to see doctors on time. The athletes <18 years of age had a higher risk of eye injuries (odds ratio [] =1.60, 95% : 1.06-2.40). The athletes with lower family income (<1,000 RMB) were at risk population for sports-related eye injuries ( = 3.91, 95% : 2.24-6.82). Training >4 h a day increased the risk of eye injuries ( = 2.21, 95% : 1.42-3.43). The incidence of sports-related eye injuries among athletes was 10.7% in Tianjin, China. Handball, water polo, and diving were the most common activities of injury. Age, family income, and training time were the risk factors for sports-related eye injuries.
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http://dx.doi.org/10.3389/fmed.2021.690528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481368PMC
September 2021

Supply chain coordination strategy for NEVs based on supplier alliance under dual-credit policy.

PLoS One 2021 1;16(10):e0257505. Epub 2021 Oct 1.

School of Economics and Business Administration, Chongqing University, Chongqing, China.

In this paper, we assume that the supply chain for new energy vehicles (NEVs) consists of a manufacturer and N parts suppliers, considering that the R&D investment of both manufacturer and suppliers will affect the market demand of NEVs and NEVs credit, we construct decentralized and centralized decision-making models under the dual-credit policy to study the R&D investment strategy of supply chain enterprises. Furthermore, considering that suppliers can form alliances, we establish bargaining game models under the conditions of the non-alliance and alliance of suppliers, and discuss the coordination strategy for the NEVs supply chain. It is found that, under the dual-credit policy, the higher the credit coefficient of technology improvement, the higher the transaction price of credits, and the higher the R&D investment of supply chain. Dual-credit policy can effectively encourage NEVs supply chain to increase R&D investment, improve NEV technology level, and improve the profit of supply chain. Under the dual-credit policy, the increment profit distribution strategy based on a bargaining game model can coordinate the NEVs supply chain. When suppliers separately negotiate with the manufacturer, bringing the negotiation sequence forward, the supplier can get more profits. However, as the manufacturer has the right to determine the negotiation sequence, the supplier can only get the profit of the last round of negotiation, and the manufacturer can get excess profit. Forming a suppliers alliance can solve this problem effectively, and increase the profit of all suppliers when the alliance`s negotiating power is improved to a certain threshold.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257505PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486137PMC
October 2021

Functional Analysis of Keto-Acid Reductoisomerase ILVC in the Entomopathogenic Fungus .

J Fungi (Basel) 2021 Sep 8;7(9). Epub 2021 Sep 8.

Anhui Provincial Key Laboratory of Microbial Pest Control, Anhui Agricultural University, Hefei 230036, China.

Ketol-acid reductoisomerase (ILVC) is the second enzyme in the branched-chain amino acid (BCAA) biosynthesis, which regulates many physiological activities in a variety of organisms from bacteria to fungi and plants. In this work, function mechanisms of ILVC in Metchnikoff (Hypocreales: Clavicipitaceae) were explored with site-directed mutagenesis, reductase activity assays and transcriptomics analysis. The reductase activity assays showed that ILVC from phytopathogenic fungi exhibited significantly higher activities than those from entomopathogenic fungi but lower than those from yeast. Site-directed mutagenesis and enzymatic activities of MrILVC with different active-site mutants (Arg-113, Ser-118, Asp-152, Asp-260, and Glu-264) confirmed that active sites of MrILVC are conserved with plant and bacterial ILVCs. Deleting causes the complete failures of vegetative growth and conidial germination, feeding with branched-chain amino acids (BCAAs) recovers the fungal growth but not conidial germination, while both characteristics are restored when supplemented with yeast extract. Compared to Δ cultured in czapek agar (CZA), plenty of genes involved in the biosynthesis of antibiotics and amino acids were up- or down-regulated in the wild type or Δ feeding with either BCAAs or yeast extract. Further analysis showed some genes, such as , participate in mycelial growth and conidial germination was down-regulated in Δ from CZA, revealing that MrILVC might control the fungal development by gene regulation and BCAAs or yeast extract could play partial roles of MrILVC. This study will advance our understanding of ILVC function mechanisms in fungi.
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http://dx.doi.org/10.3390/jof7090737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471054PMC
September 2021

Mast cells-derived exosomes worsen the development of experimental cerebral malaria.

Acta Trop 2021 Sep 22;224:106145. Epub 2021 Sep 22.

Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China; Department of Pathogen Biology and Immunology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China. Electronic address:

Cerebral malaria (CM) is the most severe neurological complication caused by Plasmodium falciparum infection. The accumulating evidence demonstrated that mast cells (MCs) and its mediators played a critical role in mediating malaria severity. Earlier studies identified that exosomes were emerging as key mediators of intercellular communication and can be released from several kinds of MCs. However, the potential functions and pathological mechanisms of MCs-derived exosomes (MCs-Exo) impacting on CM pathogenesis remain largely unknown. Herein, we utilized an experimental CM (ECM) model (C57BL/6 mice infected with P. berghei ANKA strain), and then intravenously (i.v.) injected MCs-Exo into P. berghei ANKA-infected mice to unfold this mechanism and investigate the effect of MCs-Exo on ECM pathogenies. We also used an in vitro model by investigating the pathogenesis development of brain microvascular endothelial cells line (bEnd.3 cells) co-cultured with P. berghei ANKA blood-stage soluble antigen (PbAg) after MCs-Exo treatment. The higher numbers of MCs and levels of MCs degranulation were observed in skin, cervical lymph node, and brain of ECM mice than those of the uninfected mice. Exosomes were successfully isolated from culture supernatants of mouse MCs line (P815 cells) and characterized by spherical vesicles with the diameter of 30-150 nm, and expression of typical exosomal markers (e.g., CD9, CD63, and CD81). The i.v. injection of MCs-Exo dramatically elevated incidence of ECM in the P. berghei ANKA-infected mice, exacerbated liver and brain histopathological damage, promoted Th1 cytokine response, aggravated brain vascular endothelial activation and blood brain barrier breakdown in ECM mice. In addition, the treatment of MCs-Exo led to the decrease of cells viability and mRNA levels of Ang-1, ZO-1, and Claudin-5, but increase of mRNA levels of Ang-2, CCL2, CXCL1, and CXCL9 in bEnd.3 cells co-cultured with PbAg in vitro. Taken together, our data indicated that MCs-Exo could worsen pathogenesis of ECM in mice.
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http://dx.doi.org/10.1016/j.actatropica.2021.106145DOI Listing
September 2021

A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons.

Elife 2021 09 22;10. Epub 2021 Sep 22.

Department of Bioengineering and Therapeutic Sciences and Programs in BiologicalSciences and Human Genetics, University of California, San Francisco, San Francisco, United States.

Parkinson's disease (PD) is a common neurodegenerative disorder without effective disease-modifying therapeutics. Here, we establish a chemogenetic dopamine (DA) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening. We use this system to conduct an in vivo DA neuron imaging-based chemical screen and identify the Renin-Angiotensin-Aldosterone System (RAAS) inhibitors as significantly neuroprotective. Knockdown of the angiotensin receptor 1 () in DA neurons reveals a cell-autonomous mechanism of neuroprotection. DA neuron-specific RNA-seq identifies mitochondrial pathway gene expression that is significantly restored by RAAS inhibitor treatment. The neuroprotective effect of RAAS inhibitors is further observed in a zebrafish Gaucher disease model and -deficient PD model. Finally, examination of clinical data reveals a significant effect of RAAS inhibitors in delaying PD progression. Our findings reveal the therapeutic potential and mechanisms of targeting the RAAS pathway for neuroprotection and demonstrate a salient approach that bridges basic science to translational medicine.
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http://dx.doi.org/10.7554/eLife.69795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457844PMC
September 2021

Correlation analysis of TGF-β1 Gene polymorphism and expression with incidence and severity of lumbar disc herniation.

Minerva Med 2021 Sep 20. Epub 2021 Sep 20.

Department of Spinal Surgery, Jinan Number Four Hospital, Jinan, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07736-3DOI Listing
September 2021

Ir-based electrocatalysts promoted by TME-substituted polyoxovanadate-derived vanadium carbide for efficient hydrogen evolution and oxygen evolution.

Chem Commun (Camb) 2021 Oct 7;57(80):10395-10398. Epub 2021 Oct 7.

Institute of POM-Based Materials, Hubei Provincial Key Laboratory of Green Materials for Light Industry, Hubei University of Technology, Wuhan, 430068, China.

A novel trimethylolethane (TME)-substituted polyoxovanadate (POV) was designed as a precursor to prepare ultrasmall vanadium carbide nanoparticles, which markedly promoted the hydrogen evolution reaction and oxygen evolution reaction of iridium (Ir)-based electrocatalysts. This work is the first example employing organic ligand-substituted POV as the precursor for metal carbide, and is also the first combination of Ir and vanadium carbide, providing new insights into the design of excellent electrocatalysts.
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http://dx.doi.org/10.1039/d1cc03559bDOI Listing
October 2021

Molecular characterization of two dsRNAs that could correspond to the genome of a new mycovirus that infects the entomopathogenic fungus Beauveria bassiana.

Arch Virol 2021 Nov 17;166(11):3233-3237. Epub 2021 Sep 17.

Anhui Provincial Key Laboratory of Microbial Pest Control, Anhui Agricultural University, Hefei, 230036, China.

The entomopathogenic fungus Beauveria bassiana is used worldwide for biological control of insects. Seven dsRNA segments were detected in a single B. bassiana strain, RCEF1446. High-throughput sequencing indicated the presence of three mycoviruses in RCEF1446. Two were identified as the known mycoviruses Beauveria bassiana victorivirus 1 and Beauveria bassiana polymycovirus 1, and the novel mycovirus was designated as "Beauveria bassiana bipartite mycovirus 1" (BbBV1). The complete sequence of the BbBV1 is described here. The mycovirus contains two dsRNA segments. The RNA 1 (dsRNA 4) of BbBV1 is 2,026 bp in length, encoding a RNA-dependent RNA polymerase (RdRp) (68.54 kDa), while the RNA 2 (dsRNA 6) is 1,810 bp in length, encoding a hypothetical protein (35.55 kDa) with unknown function. Moreover, the amino acid sequence of RdRp showed the highest sequence identity of 62.31% to Botryosphaeria dothidea bipartite mycovirus 1. Phylogenetic analysis based on RdRp sequences revealed that BbBV1 represents a distinct lineage of unassigned dsRNA mycoviruses infecting fungi.
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http://dx.doi.org/10.1007/s00705-021-05239-zDOI Listing
November 2021

Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis.

Am J Cancer Res 2021 15;11(8):3841-3856. Epub 2021 Aug 15.

Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University Nanchang, China.

Chemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown. In the present study, we first established two independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR. We found that GR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Our findings suggested that downregulation of NEAT1 enhanced the sensitivity of GR cells to gemcitabine by reversing the EMT process. Mechanistically, NEAT1 mediates ZEB2 mRNA expression through sponging miR-506-3p. Downregulation of NEAT1 can reverse the EMT process of GR PC cells by reducing the expression of ZEB2, thus enhancing the sensitivity of GR PC cells to gemcitabine. These findings were further confirmed in a nude mouse xenograft model. Taken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide the novel evidence for understanding the function and molecular mechanism of NEAT1, and a new direction for improving the chemotherapeutic effects in PC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414385PMC
August 2021

Mr-AbaA Regulates Conidiation by Interacting with the Promoter Regions of Both and in Metarhizium robertsii.

Microbiol Spectr 2021 Sep 8:e0082321. Epub 2021 Sep 8.

Anhui Provincial Key Laboratory of Microbial Pest Control, Anhui Agricultural Universitygrid.411389.6, Hefei, China.

Conidiation is a pivotal strategy for fungi to resist adverse environments and disperse to new habitats, which is especially important for entomopathogenic fungi whose conidia are infective as fungal pesticide propagules. However, the molecular mechanism for regulating conidiation in entomopathogenic fungi is not fully understood. Here, we characterized the regulatory mechanism of the key developmental transcription factor Mr-AbaA. Bioinformatic analysis, transcriptional profiles, and subcellular localization of indicated that AbaA functioned as a transcription factor in the conidiophore development and conidium stages. Microscopic examination showed that the null mutant of differentiated into defective phialides to produce an abacus structure instead of conidia. Loss of resulted in the inhibition of submerged blastospore separation . Moreover, yeast (Saccharomyces cerevisiae) one-hybrid assays of interactions between genes and deletion of showed that Mr-AbaA regulates conidiation by interacting with the promoter regions of and . These results demonstrate that Mr-AbaA positively regulates conidiation in Metarhizium robertsii by regulating the family ortholog gene and contributes to the separation of blastospores in submerged culture. Metarhizium robertsii is an emerging model entomopathogenic fungus for developing biopesticides; therefore, a comprehensive understanding of its conidiation is very important for its application. In this study, we revealed that the transcription factor Mr-AbaA is involved in the control of aerial conidiation and blastospore separation in submerged culture. Further yeast one-hybrid assays demonstrated that Mr-AbaA interacts with the promoter regions of and , which code for proteins involved in the control of conidiation. This finding provides new insight into the regulation of the conidiation of this important entomopathogenic fungi.
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http://dx.doi.org/10.1128/Spectrum.00823-21DOI Listing
September 2021

Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial.

Blood Adv 2021 09;5(17):3387-3396

Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom.

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti-PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of >90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post-allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.
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http://dx.doi.org/10.1182/bloodadvances.2021004511DOI Listing
September 2021

Host-Guest Interactions Between Metal-Organic Frameworks and Air-Sensitive Complexes at High Temperature.

Authors:
Bo Huang Zhe Tan

Front Chem 2021 3;9:706942. Epub 2021 Aug 3.

Institute of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, China.

The host-guest chemistry of metal-organic frameworks (MOFs) has been attracting increasing attention owing to the outstanding properties derived from MOFs-guests combinations. However, there are large difficulties involved in the syntheses of the host-guest MOF systems with air-sensitive metal complexes. In addition, the behaviors on host-guest interactions in the above systems at high temperature are not clear. This study reported the synthetic methods for host-guest systems of metal-organic framework and air-sensitive metal complexes via a developed chemical vapor infiltration process. With the synchrotron X-ray powder diffraction (XRPD) measurements and Fourier Transform infrared spectroscopy (FTIR), the successful loadings of Fe(CO) in HKUST-1 and NH-MIL-101(Al) have been confirmed. At high temperatures, the structural and chemical componential changes were investigated in detail by XRPD and FTIR measurements. HKUST-1 was proven to have strong interaction with Fe(CO) and resulted in a heavy loading amount of 63.1 wt%, but too strong an interaction led to deformation of HKUST-1 sub-unit under heating conditions. NH-MIL-101(Al), meanwhile, has a weaker interaction and is chemically inert to Fe(CO) at high temperatures.
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http://dx.doi.org/10.3389/fchem.2021.706942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369409PMC
August 2021

Circ_0006174 promotes colorectal cancer progression by sponging microRNA-142-3p and regulating X-linked inhibitor of apoptosis expression.

Int J Biol Markers 2021 Aug 19:17246008211034178. Epub 2021 Aug 19.

Department of Gastroenterology, 56663Guizhou Provincial People's Hospital, China.

Background: Circular RNAs (circRNAs) are crucial in the regulation of gene expression and biological processes. However, in colorectal cancer, the expression characteristics and biological function of circRNA_0006174 (circ_0006174) is not fully understood. This work is aimed to investigate the biological function of circ_0006174 in colorectal cancer and its molecular mechanism.

Methods: Circ_0006174, microRNA-142-3p and X-linked inhibitor of apoptosis expression levels were detected in colorectal cancer tissues and cells using quantitative real-time polymerase chain reaction analysis or Western blot. The effects of circ_0006174 on colorectal cancer cell proliferation, apoptosis, migration and invasion were detected using the cell counting kit-8 method, bromodeoxyuridine experiments, flow cytometry analysis and Transwell experiments. The targeting relationship among circ_0006174, microRNA-142-3p and X-linked inhibitor of apoptosis was analysed by bioinformatics prediction, dual-luciferase reporter experiment and RNA immunoprecipitation experiment.

Results: Circ_0006174 was up-regulated in colorectal cancer tissues as well as in cell lines, and its high expression was remarkably associated with enlarged tumour volume and advanced tumour, node, metastasis stage of the patients. Circ_0006174 overexpression enhanced colorectal cancer cell proliferation, migration and invasion, and inhibited colorectal cancer cell apoptosis; while knocking down circ_0006174 caused the opposite effects. Circ_0006174 directly targeted and negatively regulated microRNA-142-3p expression, and X-linked inhibitor of apoptosis, a target gene of microRNA-142-3p, could be indirectly and positively modulated by circ_0006174.

Conclusion: Circ_0006174 facilitates colorectal cancer cell proliferation, migration and invasion, and represses colorectal cancer cell apoptosis by regulating microRNA-142-3p/X-linked inhibitor of apoptosis axis.
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http://dx.doi.org/10.1177/17246008211034178DOI Listing
August 2021

Neonatal Outcomes of Embryos Cultured in a Time-Lapse Incubation System: an Analysis of More Than 15,000 Fresh Transfer Cycles.

Reprod Sci 2021 Aug 18. Epub 2021 Aug 18.

Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

In the past 5 years, the time-lapse culture system (TLS) has gradually been applied to the field of assisted reproduction. However, there are few reports on the comparison between this system and the conventional culture system (CS) on the outcome of newborns. As a new model in embryo culture, we should pay attention to its neonatal outcomes. We examined 15,252 fresh transfer cycles processed between January 2016 and December 2019. After propensity score matching, embryos in two groups, TLS and CS, had similar rates of miscarriages, ectopic pregnancy, and live delivery (P > 0.05). Embryos in the TLS group achieved higher clinical pregnancy and implantation rates (P < 0.05). Of the perinatal and neonatal outcomes, singletons and twins were analyzed separately. No significant differences were observed in gestational age, preterm deliveries, birth weight, and sex ratio (P > 0.05). Incidences of malformations of babies delivered from CS and TLS groups were also similar between the two groups. Embryos cultured in a TLS are as safe as CS with regard to neonatal outcomes, including congenital malformations.
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http://dx.doi.org/10.1007/s43032-021-00714-zDOI Listing
August 2021

The Threshold Effects of Low-Dose-Rate Radiation on miRNA-Mediated Neurodevelopment of Zebrafish.

Radiat Res 2021 Aug 16. Epub 2021 Aug 16.

School of Public Health, University of South China, Hengyang 421001, PR China.

The biological effects and regulatory mechanisms of low-dose and low-dose-rate radiation are still rather controversial. Therefore, in this study we investigated the effects of low-dose-rate radiation on zebrafish neurodevelopment and the role of miRNAs in radiation-induced neurodevelopment. Zebrafish embryos received prolonged gamma-ray irradiation (0 mGy/h, 0.1 mGy/h, 0.2 mGy/h, 0.4 mGy/h) during development. Neurodevelopmental indicators included mortality, malformation rate, swimming speed, as well as the morphology changes of the lateral line system and brain tissue. Additionally, spatiotemporal expression of development-related miRNAs (dre-miR-196a-5p, dre-miR-210-3p, dre-miR-338) and miRNA processing enzymes genes (Dicer and Drosha) were assessed by qRT-PCR and whole mount in situ hybridization (WISH). The results revealed a decline in mortality, malformation and swimming speed, with normal histological and morphological appearance, in zebrafish that received 0.1 mGy/h; however, increased mortality, malformation and swimming speed were observed, with pathological changes, in zebrafish that received 0.2 mGy/h and 0.4 mGy/h. The expression of miRNA processing enzyme genes was altered after irradiation, and miRNAs expression was downregulated in the 0.1 mGy/h group, and upregulated in the 0.2 mGy/h and 0.4 mGy/h groups. Furthermore, ectopic expression of dre-miR-210-3p, Dicer and Drosha was also observed in the 0.4 mGy/h group. In conclusion, the effect of low-dose and low-dose-rate radiation on neurodevelopment follows the threshold model, under the regulation of miRNAs, excitatory effects occurred at a dose rate of 0.1 mGy/h and toxic effects occurred at a dose rate of 0.2 mGy/h and 0.4 mGy/h.
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http://dx.doi.org/10.1667/RADE-20-00265.1DOI Listing
August 2021

Effectiveness and safety of different traditional Chinese medicines for Coronavirus disease 2019: A protocol for systematic review and network meta-analysis.

Medicine (Baltimore) 2021 Aug;100(31):e26676

Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Introduction: The effectiveness of different Traditional Chinese Medicine in the treatment of COVID-19 is worthy of attention, but the efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 have not yet been compared, based on network meta-analysis.

Methods And Analysis: The 2 members independently searched 7 databases according to the retrieval strategy, and the retrieval time was from the beginning of the establishment of the database to June 19, 2021. Then the title was imported into the EndNote Software AQ8 (V.X9), and the duplicate literature was deleted successively, the nonconforming articles were deleted in the title reading, and finally the full text was read to determine the articles included in the study. The Cochrane Collaboration's Tool will be used to evaluate the article quality, and Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) will be used for data analysis. Levels of evidence are evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument.

Results: The efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 were evaluated, and the order was determined according to the value of sucre.

Conclusion: This study will provide evidence for the treatment of COVID-19 with TCM therapy, and provide ideas for the clinical treatment of COVID-19.

Inplasy Registration Number: No. INPLASY202160092.
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http://dx.doi.org/10.1097/MD.0000000000026676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341296PMC
August 2021

Circ_0087862 promotes the progression of colorectal cancer by sponging miR-142-3p and up-regulating BACH1 expression.

Kaohsiung J Med Sci 2021 Aug 13. Epub 2021 Aug 13.

Department of Gastroenterology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.

Circular RNAs (circRNAs) feature prominently in regulating the malignant biological behaviors of colorectal cancer (CRC), including cell viability, cell cycle progression, apoptosis, migration, invasion, and so on. This study is performed to probe into the biological function and molecular mechanism of circ_0087862 in CRC. The expression profile of GSE138589 was available from Gene Expression Omnibus (GEO), and the differentially expressed circRNAs were analyzed by GEO2R. The expression of circ_0087862, miR-142-3p, and BACH1 mRNA in CRC tissues and cells was measured by qRT-PCR. CCK-8 assay was employed to determine the proliferation of CRC cells. Scratch wound healing and transwell assays were used to examine the migration and invasion of CRC cells. The targeting relationships between circ_0087862 and miR-142-3p, and between miR-142-3p and BACH1 3'UTR were verified by dual-luciferase reporter gene assay and RIP assay. BACH1 protein expression was probed by western blot. Circ_0087862 was highly expressed in CRC tissues and cell lines. Knocking down circ_0087862 significantly restrained the multiplication, migration and invasion of CRC cells. miR-142-3p inhibition weakened the impact of circ_0087862 knockdown on CRC cells. Circ_0087862 regulated BACH1 expressions by targeting miR-142-3p. Circ_0087862 regulates BACH1 expressions through sponging miR-142-3p, and promotes the proliferation, migration, and invasion of CRC cells.
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http://dx.doi.org/10.1002/kjm2.12437DOI Listing
August 2021

Nuclear export and translation of circular repeat-containing intronic RNA in C9ORF72-ALS/FTD.

Nat Commun 2021 08 13;12(1):4908. Epub 2021 Aug 13.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

C9ORF72 hexanucleotide GGGGCC repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-containing RNA mediates toxicity through nuclear granules and dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG translation. However, it remains unclear how the intron-localized repeats are exported and translated in the cytoplasm. We use single molecule imaging approach to examine the molecular identity and spatiotemporal dynamics of the repeat RNA. We demonstrate that the spliced intron with G-rich repeats is stabilized in a circular form due to defective lariat debranching. The spliced circular intron, instead of pre-mRNA, serves as the translation template. The NXF1-NXT1 pathway plays an important role in the nuclear export of the circular intron and modulates toxic DPR production. This study reveals an uncharacterized disease-causing RNA species mediated by repeat expansion and demonstrates the importance of RNA spatial localization to understand disease etiology.
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http://dx.doi.org/10.1038/s41467-021-25082-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363653PMC
August 2021

Drivers and suppressors of triple-negative breast cancer.

Proc Natl Acad Sci U S A 2021 Aug;118(33)

Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204;

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor β (ERβ) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERβ. ERβ is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERβ TNBC patient-derived xenografts in mice and found that the ERβ agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERβ is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERβ functionless on genes involved in proliferation and inflammation.
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http://dx.doi.org/10.1073/pnas.2104162118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379974PMC
August 2021

m(6)A Modification of lncRNA NEAT1 Regulates Chronic Myelocytic Leukemia Progression miR-766-5p/CDKN1A Axis.

Front Oncol 2021 20;11:679634. Epub 2021 Jul 20.

Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Chronic myeloid leukemia (CML) is an acquired hematopoietic stem malignant disease originating from the myeloid system. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis. However, their roles in CML remain largely unclear.

Methods: The peripheral blood mononuclear cells (PBMCs) and CML cell lines (K562, KCL22, MEG01, BV173) were collected for research. Real-time quantitative polymerase chain reaction was used to determine the mRNA expression levels. Cell viability and apoptosis were analyzed by cell counting kit 8 and flow cytometry assays. The targeting relationships were predicted using Starbase and TargetScan and ulteriorly verified by RNA pull-down and luciferase reporter assays. Western blotting assay was performed to assess the protein expressions. N6-methyladenosine (m6A) modification sites were predicted by SRAMP and confirmed by Methylated RNA immunoprecipitation (MeRIP) assay.

Results: LncRNA nuclear-enriched abundant transcript 1 (NEAT1) expression levels were decreased in the CML cell lines and PBMCs of CML patients. Moreover, METTL3-mediated m6A modification induced the aberrant expression of NEAT1 in CML. Overexpression of NEAT1 inhibited cell viability and promoted the apoptosis of CML cells. Additionally, miR-766-5p was upregulated in CML PBMCs and abrogated the effects of NEAT1 on cell viability and apoptosis of the CML cells. Further, CDKN1A was proved to be the target gene of miR-766-5p and was downregulated in the CML PBMCs. Knockdown of CDKN1A reversed the effects of NEAT1.

Conclusion: The current research elucidates a novel METTL3/NEAT1/miR-766-5p/CDKN1A axis which plays a critical role in the progression of CML.
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http://dx.doi.org/10.3389/fonc.2021.679634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329653PMC
July 2021

Hypoxia Promotes Breast Cancer Cell Growth by Activating a Glycogen Metabolic Program.

Cancer Res 2021 Oct 4;81(19):4949-4963. Epub 2021 Aug 4.

Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Hypoxia is known to be commonly present in breast tumor microenvironments. Stem-like cells that repopulate breast tumors, termed tumor-repopulating cells (TRC), thrive under hypoxic conditions, but the underlying mechanism remains unclear. Here, we show that hypoxia promotes the growth of breast TRCs through metabolic reprogramming. Hypoxia mobilized transcription factors HIF1α and FoxO1 and induced epigenetic reprogramming to upregulate cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme that initiates gluconeogenesis. PCK1 subsequently triggered retrograde carbon flow from gluconeogenesis to glycogenesis, glycogenolysis, and the pentose phosphate pathway. The resultant NADPH facilitated reduced glutathione production, leading to a moderate increase of reactive oxygen species that stimulated hypoxic breast TRC growth. Notably, this metabolic mechanism was absent in differentiated breast tumor cells. Targeting PCK1 synergized with paclitaxel to reduce the growth of triple-negative breast cancer (TNBC). These findings uncover an altered glycogen metabolic program in breast cancer, providing potential metabolic strategies to target hypoxic breast TRCs and TNBC. SIGNIFICANCE: Hypoxic breast cancer cells trigger self-growth through PCK1-mediated glycogen metabolism reprogramming that leads to NADPH production to maintain a moderate ROS level.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0753DOI Listing
October 2021

Corrigendum to "Reprogramming of human peripheral blood mononuclear cells from a patient suffering from recurrent hydatidiform mole to an iPSC line FAHZUi001-A carrying a homozygous p.Gln421Ter mutation in NLRP7 gene" [Stem Cell Res. 53 (2021) 102361].

Stem Cell Res 2021 Aug 27;55:102479. Epub 2021 Jul 27.

Department of Gynecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:

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http://dx.doi.org/10.1016/j.scr.2021.102479DOI Listing
August 2021

PADI6 Regulates Trophoblast Cell Migration-Invasion Through the Hippo/YAP1 Pathway in Hydatidiform Moles.

J Inflamm Res 2021 22;14:3489-3500. Epub 2021 Jul 22.

Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, 310003, Zhejiang Province, People's Republic of China.

Purpose: Peptidyl arginine deiminase, type VI (PADI6), a member of the subcortical maternal complex, plays an important role in oocyte growth and the development of fertilized oocytes. Human patients with PADI6 mutations can suffer from multiple reproductive deficiencies including hydatidiform moles and miscarriages. Recent studies have demonstrated that the Hippo signaling pathway plays a central role in the specification of the first cell fates and the maintenance of the human placental trophoblast epithelium. The present study aimed to verify the hypothesis that PADI6 regulates the biological functions of trophoblast cells by targeting YAP1 and to explore the mechanism by which PADI6 accomplishes this in trophoblast cells.

Methods: Villi from HMs and human trophoblast cell lines were used to identify the localization of PADI6 and YAP1 by immunohistochemistry and immunocytochemistry. PADI6 overexpression and knockdown were induced in human trophoblast cells. Co-immunoprecipitation was used to explore the interaction between PADI6 and YAP1. Wound healing, Transwell and EdU staining assays were used to detect migration, invasion and proliferation. Flow cytometric analysis was used to analyze the cell cycle and apoptosis. β-Tubulin and F-actin levels were determined by Western blot, quantitative real-time PCR and phalloidin staining.

Results: The results showed that PADI6 and YAP1 had the same expression pattern in villi and colocalized in the cytotrophoblast. An interaction between PADI6 and YAP1 was also confirmed in human trophoblast cell lines. We found that PADI6 positively regulated the expression of YAP1. Functionally, overexpression of PADI6 promoted cell cycle progression and enhanced migration, invasion, proliferation and apoptosis, whereas downregulation of PADI6 showed the opposite effects.

Conclusion: This study demonstrates that YAP1 is a novel target of PADI6 that serves as an important regulator of trophoblast dysfunction. The crosstalk between the Hippo/YAP1 pathway and the SCMC might be a new topic to explore to uncover the pathological mechanisms of HMs.
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http://dx.doi.org/10.2147/JIR.S313422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314932PMC
July 2021
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