Publications by authors named "Le Xu"

258 Publications

Yap1-2 Isoform Is the Primary Mediator in TGF-β1 Induced EMT in Pancreatic Cancer.

Front Oncol 2021 19;11:649290. Epub 2021 May 19.

Institute of Life Sciences, Wenzhou University, Wenzhou, China.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive human malignancy and intrinsically resistant to conventional therapies. YAP1, as a key downstream effector of the Hippo pathway, plays an important role in tumorigenesis including PDAC. Alternative mRNA splicing of YAP1 results in at least 8 protein isoforms, which are divided into two subgroups (YAP1-1 and YAP1-2) based on the presence of either a single or double WW domains. We investigated the functions and regulatory mechanisms of YAP1-1 and YAP1-2 in PDAC cells induced by TGF-β to undergo epithelial-to-mesenchymal transition (EMT). CRISPR-Cas9 and shRNA were used to silence YAP1 expression in pancreatic cancer cells. Re-constituted lentivirus mediated overexpression of each single YAP1 isoform was generated in the parental knockout L3.6 cells. EMT was induced by treatment with TGF-β, EGF and bFGF in parental and the constructed stable cell lines. Western blot and qPCR were used to detect the expression of EMT markers. Scratch wound healing and transwell assays were used to detect cell migration. The stability and subcellular localization of YAP1 proteins were determined by Western blot analysis, immunofluorescence, as well as ubiquitination assays. We showed that TGF-β, EGF and bFGF all significantly promoted EMT in PDAC cells, which was inhibited by knockdown of YAP1 expression. Interestingly, YAP1-1 stable cells exhibited a stronger migratory ability than YAP1-2 cells under normal culture condition. However, upon TGF-β treatment, L3.6-YAP1-2 cells exhibited a stronger migratory ability than L3.6-YAP1-1 cells. Mechanistically, TGF-β treatment preferentially stabilizes YAP1-2 and enhances its nuclear localization. Furthermore, TGF-β-induced EMT and YAP1-2 activity were both blocked by inhibition of AKT signaling. Our results showed that both YAP1-1 and YAP1-2 isoforms are important mediators in the EMT process of pancreatic cancer. However, YAP1-2 is more important in mediating TGF-β-induced EMT, which requires AKT signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.649290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170464PMC
May 2021

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.

Methods: Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.

Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.

Conclusions: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab437DOI Listing
May 2021

CircMKLN1 Suppresses the Progression of Human Retinoblastoma by Modulation of miR-425-5p/PDCD4 Axis.

Curr Eye Res 2021 May 14:1-11. Epub 2021 May 14.

Department of Ophthalmology, Suizhou Hospital, Hubei University of Medicine, Suizhou City, Hubei Province, China.

: Circular RNAs (circRNAs) are essential regulators in tumorigenesis and development. In this study, we focused on the functions of circRNA muskelin 1 (circMKLN1) in retinoblastoma (RB) progression.: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the levels of circMKLN1, microRNA-425-5p (miR-425-5p) and programmed cell death 4 (PDCD4). The characteristic of circMKLN1 was analyzed using RNase R assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed to explore cell proliferation ability. The transwell assay was utilized for cell migration and invasion. A Western blot assay was performed for protein levels. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to demonstrate the relationships among circMKLN1, miR-425-5p and PDCD4. Murine xenograft model assay was adopted to investigate the role of circMKLN1 .: CircMKLN1 was downregulated in RB tissues and cells. High levels of circMKLN1 were related to a favorable outcome of RB patients. CircMKLN1 was resistant to RNase R digestion and circMKLN1 overexpression repressed RB cell proliferation, migration and invasion . MiR-425-5p was identified as the target of circMKLN1 and miR-425-5p elevation reversed the effects of circMKLN1 overexpression on RB cell malignant behaviors. Furthermore, as the target gene of miR-425-5p, PDCD4 silencing could ameliorate the suppressive roles of circMKLN1 in RB cell growth and metastasis. Additionally, circMKLN1 overexpression hampered tumor growth .: CircMKLN1 overexpression decelerated the progression of RB through sponging miR-425-5p and elevating PDCD4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2021.1927110DOI Listing
May 2021

[Latest Progresses in Surgical Treatment of Median Arcuate Ligament Syndrome].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):283-287

Department of Vascular Surgery,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Median arcuate ligament syndrome(MALS)is compression of the celiac trunk by the median arcuate ligament.Median arcuate ligament release is the corner stone for the surgical treatment of MALS.Open surgery,laparoscopic surgery,and robot-assisted surgery have been developed,among which laparoscopic surgery has been proposed as the preferred approach in view of its minimal trauma and short hospital stay.Auxiliary celiac plexus neurolysis could further alleviate the patient's discomfort.Moreover,vascular reconstitution is of vital importance in the case of persistent stenosis in the celiac artery despite of median arcuate ligament decompression.Vascular reconstruction has satisfactory long-term patency rate,while endovascular treatment is less invasive.This article aims to summarize the consensuses and advances and shed light on the surgical treatment of MALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3881/j.issn.1000-503X.11980DOI Listing
April 2021

Overexpression of retinoid X receptor beta provides protection against oxidized low-density lipoprotein-induced inflammation via regulating PGC1α-dependent mitochondrial homeostasis in endothelial cells.

Biochem Pharmacol 2021 Jun 17;188:114559. Epub 2021 Apr 17.

Department of Pharmacology, Nantong University Pharmacy College, Nantong 226001, China. Electronic address:

Retinoid X receptor beta (RXRβ) has been poorly studied in atherosclerosis. The aim of the present study is to explore the function of RXRβ in oxidized low density lipoprotein (ox-LDL)-induced inflammation in endothelial cells and the underlying mechanism. The protein expression of RXRβ in the aorta of atherosclerotic mice was detected. A lentivirus vector for RXRβ overexpression and RNA interference for RXRβ downregulation were constructed and transfected into human aortic endothelial cells (HAECs). The results showed that RXRβ protein expression was downregulated in aorta of high fat diet (HFD)-fed LDLr mice and ox-LDL-treated HAECs. The ox-LDL-induced production of pro-inflammatory cytokines and activations of TLR9/NF-κB and NLRP3/caspase-1 inflammasome pathway were significantly decreased by RXRβ overexpression but increased by RXRβ knockdown in HAECs. The ox‑LDL‑induced mitochondrial damage indicated as the increased generation of mitochondrial ROS, decreased mitochondrial membrane potential and increased mitochondrial DNA release was abolished by RXRβ overexpression but aggravated by RXRβ knockdown. Treatment with mito-TEMPO significantly reduced the increased production of pro-inflammatory cytokines and activations of TLR9/NF-κB and NLRP3/caspase-1 inflammasome induced by RXRβ knockdown in ox-LDL treated HAECs. Moreover, peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α) protein expression was reduced in HFD-fed LDLr mice. RXRβ could interact with PGC1α in HAECs. Ox-LDL-induced reduction of PGC1α was significantly inhibited by RXRβ overexpression and aggravated by RXRβ downregulation. Our further study showed that transfection of PGC1α siRNA abrogated the alleviative effects of RXRβ overexpression on mitochondrial damage and inflammation in ox-LDL treated cells. The present study indicates that RXRβ exerted protective effects against the ox-LDL-induced inflammation may through regulating PGC1α-dependent mitochondrial homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2021.114559DOI Listing
June 2021

Intratumoral CXCL13CD8T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma.

J Immunother Cancer 2021 Feb;9(2)

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

Background: Chemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4T cells (T) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by T have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13CD8T cells in clear cell renal cell carcinoma (ccRCC).

Methods: We analyzed prognostic value and immune contexture that associated with CXCL13CD8T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13CD8T cells and total CD8T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC.

Results: Intratumoral CXCL13CD8T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13CD8T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8T cells in high-level CXCL13CD8T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13CD8T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3 regulatory T cells, TLS and decreased natural killer cells, GZMB cells.

Conclusions: Intratumoral CXCL13CD8T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13CD8T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13CD8T cells abundance impaired total CD8T cells' immune function. Intratumoral CXCL13CD8T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13CD8T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-001823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887366PMC
February 2021

Oral administration of promotes antitumor efficacy via dendritic cells-derived interleukin 12.

Oncoimmunology 2021 01 15;10(1):1868122. Epub 2021 Jan 15.

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.

Recent advances in immunotherapy, as a part of the multidisciplinary therapy, has gradually gained more attention. However, only a small proportion of patients who sensitive to the therapy could gain benefits. An increasing number of studies indicate that intestinal microbiota could enhance the efficiency of cancer immunotherapy. As one of the main probiotics, plays an important role in immune regulation, which has been proved by animal research and human clinical study. But the detailed mechanism was not clearly elucidated. Here we found oral administration of () lw01 could significantly inhibit tumor growth and up-regulate tumor cell apoptosis, which relied on the recruitment of tumor-infiltrating lymphocytes and dendritic cells (DCs) in tumor microenvironment, but not () CGMCC 1.3724 or () MG1655. In the ligated intestine loop model, 's stimulation triggered the upregulated expression of DC-related chemokine CCL20 and recruited more DCs in the intestinal villi. Further study revealed the enhancement of interleukin 12 (IL-12) secretion derived from DCs is essential to 's antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1868122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833736PMC
January 2021

Characterization of a Molecule Partially Confined at the Pore Mouth of a Zeotype.

Angew Chem Int Ed Engl 2021 04 17;60(18):10239-10246. Epub 2021 Mar 17.

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, 94720, USA.

We investigate the interaction between a molecule and a pore mouth-a critical step in adsorption processes-by characterizing the conformation of a macrocyclic calix[4]arene-Ti complex, which is grafted on the external surface of a zeotype (*-SVY). X-ray absorption and C{ H} CPMAS NMR spectroscopies independently detect a unique conformation of this complex when it is grafted at crystallographically equivalent locations that lie at the interface of 7 Å hemispherical microporous cavities and the external surface. Electronic structure calculations support the presence of this unique conformation, and suggest that it is brought about by a specific orientation of the macrocycle that maximizes non-covalent interactions between calix[4]arene upper-rim tert-butyl substituents and the microporous-cavity walls. Our comparative study provides a rare "snapshot" of a molecule partially confined at a pore mouth, an essential intermediate for adsorption into micropores, and demonstrates how surrounding environment controls this confinement in a sensitive fashion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202100166DOI Listing
April 2021

Identification and validation of poor prognosis immunoevasive subtype of muscle-invasive bladder cancer with tumor-infiltrating podoplanin cell abundance.

Oncoimmunology 2020 04 3;9(1):1747333. Epub 2020 Apr 3.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

The choice of chemo- or immuno-therapy for muscle-invasive bladder cancer (MIBC) patients remains contentious. Podoplanin is newly identified as an immune checkpoint which intrigues us to explore the clinical significance and immunoregulatory role of tumor-infiltrating podoplanin cells (PDPN cells) in MIBC. A retrospective analysis of 259 MIBC patients from Zhongshan Hospital (n = 141) and Shanghai Cancer Center (n = 118) was conducted. A total of 406 MIBC patients from TCGA database were enrolled to investigate the relationship between PDPN and molecular characterization. We found that tumor-infiltrating PDPN cell abundance indicated an inferior overall survival and recurrence-free survival. pT2 MIBC patients with PDPN cell low infiltration could benefit more from adjuvant chemotherapy (ACT). Increased PDPN cell infiltration was associated with diminished GZMB and TNF-α expression while correlated with expanded PD-1, PD-L1, LAG-3 and TIM-3 expression and tumor-promoting regulatory T cell and M2 macrophage infiltration. Tumors with high PDPN mRNA expression mainly presented luminal-infiltrated and basal-squamous subtypes (2017 TCGA classification) or stroma-rich and Ba/Sq subtypes (consensus classification). Elevated PDPN mRNA expression was associated with less FGFR3 activation signature and more T-cell-inflamed signature and EGFR activation signature. In conclusion, tumor-infiltrating PDPN cells could be applied as an independent prognosticator for clinical outcome and a predictive biomarker for suboptimal ACT responsiveness, which was also associated with immunosuppressive contexture infiltration. Intratumoral PDPN expression had a correlation with MIBC molecular classification and therapy-related signatures. The novel immune checkpoint PDPN should be considered as a possible immunotherapeutic target for MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1747333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759386PMC
April 2020

Diminished excitatory synaptic transmission correlates with impaired spatial working memory in neurodevelopmental rodent models of schizophrenia.

Pharmacol Biochem Behav 2021 Mar 12;202:173103. Epub 2021 Jan 12.

Zhejiang Key Laboratory of Pathophysiology, Department of Pharmacology, Ningbo University School of Medicine, 818 Fenghua Rd, Ningbo, Zhejiang 315211, China; Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, Zhejiang 315010, China. Electronic address:

Neurodevelopmental abnormalities are associated with cognitive dysfunction in schizophrenia. In particular, deficits of working memory, are consistently observed in schizophrenia, reflecting prefrontal cortex (PFc) dysfunction. To elucidate the mechanism of such deficits in working memory, the pathophysiological properties of PFc neurons and synaptic transmission have been studied in several developmental models of schizophrenia. Given the pathogenetic heterogeneity of schizophrenia, comparison of PFc synaptic transmission between models of prenatal and postnatal defect would promote our understanding on the developmental components of the biological vulnerability to schizophrenia. In the present study, we investigated the excitatory synaptic transmission onto pyramidal cells localized in layer 5 of the medial PFc (mPFc) in two developmental models of schizophrenia: gestational methylazoxymethanol acetate (MAM) administration and post-weaning social isolation (SI). We found that both models exhibited defective spatial working memory, as indicated by lower spontaneous alternations in a Y-maze paradigm. The recordings from pyramidal neurons in both models exhibited decreased spontaneous excitatory postsynaptic current (sEPSC), representing the reduction of excitatory synaptic transmission in the mPFc. Interestingly, a positive correlation between the impaired spontaneous alternation behavior and the decreased excitatory synaptic transmission of pyramidal neurons was found in both models. These findings suggest that diminished excitatory neurotransmission in the mPFc could be a common pathophysiology regardless of the prenatal and postnatal pathogenesis in developmental models of schizophrenia, and that it might underlie the mechanism of defective working memory in those models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbb.2021.173103DOI Listing
March 2021

Identification and Analysis of MicroRNAs Associated with Wing Polyphenism in the Brown Planthopper, .

Int J Mol Sci 2020 Dec 21;21(24). Epub 2020 Dec 21.

State Key Laboratory of Rice Biology & Ministry of Agricultural and Rural Affairs Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Institute of Insect Sciences, Zhejiang University, Hangzhou 310058, China.

Many insects are capable of developing two types of wings (i.e., wing polyphenism) to adapt to various environments. Though the roles of microRNAs (miRNAs) in regulating animal growth and development have been well studied, their potential roles in modulating wing polyphenism remain largely elusive. To identify wing polyphenism-related miRNAs, we isolated small RNAs from 1st to 5th instar nymphs of long-wing (LW) and short-wing (SW) strains of the brown planthopper (BPH), . Small RNA libraries were then constructed and sequenced, yielding 158 conserved and 96 novel miRNAs. Among these, 122 miRNAs were differentially expressed between the two BPH strains. Specifically, 47, 2, 27 and 41 miRNAs were more highly expressed in the 1st, 3rd, 4th and 5th instars, respectively, of the LW strain compared with the SW strain. In contrast, 47, 3, 29 and 25 miRNAs were more highly expressed in the 1st, 3rd, 4th and 5th instars, respectively, of the SW strain compared with the LW strain. Next, we predicted the targets of these miRNAs and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We found that a number of pathways might be involved in wing form determination, such as the insulin, MAPK, mTOR, FoxO and thyroid hormone signaling pathways and the thyroid hormone synthesis pathway. Thirty and 45 differentially expressed miRNAs targeted genes in the insulin signaling and insect hormone biosynthesis pathways, respectively, which are related to wing dimorphism. Among these miRNAs, , and , were confirmed to interact with s (s) in dual luciferase reporter assays. These discoveries are helpful for understanding the miRNA-mediated regulatory mechanism of wing polyphenism in BPHs and shed new light on how insects respond to environmental cues through developmental plasticity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767257PMC
December 2020

[Scrotoscopy in the diagnosis and treatment of testicular and epididymal diseases: Analysis of 39 cases].

Zhonghua Nan Ke Xue 2020 Feb;26(2):134-138

Department of Urology, He Xian Memorial Hospital Affiliated to Southern Medical University, Guangzhou, Guangdong 511400, China.

Objective: To investigate the efficiency, safety and clinical application value of scrotoscopy in the diagnosis and treatment of testicular and epididymal diseases.

Methods: A total of 39 patients with testicular or epididymal diseases underwent scrotoscopic surgery in our hospital from February 2015 to February 2018. We retrospectively analyzed the clinical data, results of surgery, and postoperative scrotal pain scores, complications and recurrence.

Results: Scrotoscopic surgery was successfully performed in all the 39 cases, without such severe complications as testis rupture and scrotal hematoma. Thirteen cases of epididymal tumor were treated by total excision of the tumors by laser ablation; 10 of the 12 patients complaining of chronic testicular pain were diagnosed with incomplete torsion of testicular or epididymal appendages and treated by holmium laser ablation; of the 11 cases of suspected testicular torsion, 8 were confirmed as testicular torsion and the other 3 as acute epididymitis; and 3 cases of scrotal trauma-induced old hematoma underwent surgical removal under the scrotoscope. No infection of scrotal incision occurred postoperatively. The visual analog pain scores of the patients averaged 3.4 ± 1.2 (2-5) and their hospital stay 3.2 ± 0.8 (3-6) days. Scrotal ultrasonography at 1 month after surgery revealed no abnormality in the testis, epididymis or spermatic cord.

Conclusions: Scrotoscopy is safe and effective for the diagnosis and treatment of testicular and epididymal diseases and deserves a wide clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2020

Structure-direction towards the new large pore zeolite NUD-3.

Chem Commun (Camb) 2021 Jan 9;57(2):191-194. Epub 2020 Dec 9.

Instituto de Ciencia de Materiales de Madrid, Consejo Superior de Investigaciones Científicas (ICMM-CSIC) c/Sor Juana Inés de la Cruz 3, Madrid 28049, Spain.

The new zeolite NUD-3 possesses a three-dimensional system of large pore channels that is topologically identical to those of ITQ-21 and PKU-14. However, the three zeolites have distinctly different frameworks: a particular single 4-membered ring inside the denser portion of the zeolite is missing in PKU-14, disordered in ITQ-21 and fully ordered in NUD-3. We document these differences and use molecular simulations to unravel the mechanism by which a particular structure directing agent dication, 1,1'-(1,2-phenylenebis(methylene))bis(3-methylimidazolium), is able to orient this inner ring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc07333dDOI Listing
January 2021

Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.

Bioorg Med Chem 2021 01 26;29:115891. Epub 2020 Nov 26.

Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China; Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address:

Ryanodine receptors (RyRs) are important ligand-gated Ca channels; their excessive activation leads to Ca leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca release as evidenced by store overload-induced Carelease (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 μM, 3 μM and 10 μM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2020.115891DOI Listing
January 2021

Diverse crystal size effects in covalent organic frameworks.

Nat Commun 2020 Nov 30;11(1):6128. Epub 2020 Nov 30.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 730000, Lanzhou, Gansu, P.R. China.

Crystal size effect is of vital importance in materials science by exerting significant influence on various properties of materials and furthermore their functions. Crystal size effect of covalent organic frameworks (COFs) has never been reported because their controllable synthesis is difficult, despite their promising properties have been exhibited in many aspects. Here, we report the diverse crystal size effects of two representative COFs based on the successful realization of crystal-size-controlled synthesis. For LZU-111 with rigid spiral channels, size effect reflects in pore surface area by influencing the pore integrity, while for flexible COF-300 with straight channels, crystal size controls structural flexibility by altering the number of repeating units, which eventually changes sorption selectivity. With the understanding and insight of the structure-property correlation not only at microscale but also at mesoscale for COFs, this research will push the COF field step forward to a significant advancement in practical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-19858-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705719PMC
November 2020

Diagnosis of thyroid neoplasm using support vector machine algorithms based on platelet RNA-seq.

Endocrine 2021 Jun 12;72(3):758-783. Epub 2020 Nov 12.

Department of Head and Neck Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong District, Shanghai, 200127, China.

Objective: To assess the capacity of support vector machine (SVM) algorithms that are developed based on platelet RNA-seq data in identifying thyroid neoplasm patients and differentiating patients with thyroid adenomas, papillary thyroid cancer and metastasized papillary thyroid cancer.

Methods: Platelets were collected and isolated from 109 patients and 63 healthy controls. RNA-seq was performed to find transcripts with differential levels. Genes corresponding to these altered transcripts were identified using R packages. All samples were subsampled into a training set and a validation set. Two SVM algorithms were developed and trained with the training set, using the genes with differential transcript levels (GDTLs) as classifiers, and validated with the validation set. GO and KEGG pathway enrichment analysis were performed using the R package clusterProfiler.

Results: We detected 765 GDTLs (442 up-regulated and 323 down-regulated) in platelets of patients and healthy controls. The algorithm identifying thyroid neoplasm patients achieved an accuracy of 97%, with an AUC (area under curve) of 0.998. The other algorithm differentiating patients with multiclass thyroid neoplasms had an average accuracy of 80.5%. GO analysis showed that GDTLs were strongly involved in biological processes such as neutrophil degranulation, neutrophil activation, autophagy and regulation of multi-organism process. KEGG pathway enrichment analysis revealed that GDTLs were mainly enriched in NOD-like receptor signaling pathway and pathways in endocytosis, osteoclast differentiation, human cytomegalovirus infection and tuberculosis.

Conclusion: Our results indicated that the combination of SVM algorithms and platelet RNA-seq data allowed for thyroid neoplasm diagnostics and multiclass thyroid neoplasm classification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-020-02523-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159845PMC
June 2021

Tumor-infiltrating TNFRSF9 CD8 T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response.

Oncoimmunology 2020 10 27;9(1):1838141. Epub 2020 Oct 27.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Objectives: Tumor necrosis receptor super family (TNFRSF) plays an important role in regulating the function of CD8 T cells. In this study, we explored the clinical significance and immune profile of TNFRSF9 CD8 T cells in clear cell renal cell carcinoma (ccRCC).

Methods: The infiltration of immune cells was determined by immunohistochemistry in ZS cohort from our hospital and their prognostic value was further determined by Cox regression. Functional status of CD8 T cells in ccRCC was determined by flow cytometry in 29 fresh tumor samples. In silico analysis on a TCGA cohort and other datasets was performed to further demonstrate our findings.

Results: High TNFRSF9 CD8 T cells infiltration was associated with inferior overall survival in ZS cohort ( = .0016) and TCGA-KIRC cohort ( = .018). TNFRSF9 CD8 T cells expressed higher exhaustion markers (PD-1, TIM-3, CTLA-4, and TIGIT), and effector markers (IFN-γ, GZMB, CD107a, and Ki-67), than their TNFRSF9 negative counterparts. In silico analysis indicated the expression of TNFRSF9 was significantly correlated with IFNG, GZMK, MKI-67, PDCD1, HAVCR2, TIGIT, and CTLA-4 in CD8 T cells. However, higher TNFRSF9 signature was correlated with larger tumor size shrinkage ( = .003) and better progression-free survival ( = .012) in patients treated with nivolumab but not everolimus.

Conclusion: TNFRSF9 CD8 T cells, which possessed both exhaustion and effector phenotype, were identified as an adverse prognosticator in ccRCC. These cells enrichment was associated with better immunotherapy response which indicated these cells potentially be crucial in immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1838141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595587PMC
October 2020

Ultrasonic effects on the headspace volatilome and protein isolate microstructure of duck liver, as well as their potential correlation mechanism.

Ultrason Sonochem 2021 Mar 7;71:105358. Epub 2020 Oct 7.

Key Laboratory of Animal Protein Food Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Science, Ningbo University, Ningbo 315211, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, China; National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.

In spite of the high added value and tremendous output from duck processing industries, duck liver (DLv) is underutilized and a major factor is related to its prominent off-flavor perception which hampers the consumption and processing attributes. This work was designed to investigate the impact of low-frequency ultrasound (US) pretreatments on the headspace volatilome evolution of DLv and its isolated protein (DLvP) microstructure, aiming at exploring the potential of US technology to inhibit off-flavor perception and possible mechanisms behind. Results suggested that US pretreatment resulted in decreased lipid oxidation and off-flavor perception, simultaneously without significantly causing physicochemical influence including texture, pH and color. US induced obvious tertiary structural changes of DLvP, as revealed by the intrinsic fluorescence and surface hydrophobicity (H0), whereas the SH, S-S, secondary structure and molecular weight of DLvP remained unaffected, suggesting the presence of molten globule state (MG-state) under ultrasonic conditions. Besides, the headspace contents of flavor compounds, mainly aldehydes and alcohols, were significantly decreased whereas acids were increased. Multivariate analysis suggested an obvious US-induced effect on the volatilome evolution of DLv samples. Discriminant analysis recognized the aroma compounds including aldehydes and alkenals as the major contributors leading to the change of olfactory characteristics of DLv after ultrasonic treatment. Correlation analysis demonstrated the positive relationship between the volatile markers variation and the increased H0 values, a characteristic attribute of MG-state protein. The results obtained in this work suggested that US technology matched with suitable parameters could be a very promising approach to modulate the off-flavor perception of liver products by altering DLvP conformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultsonch.2020.105358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786588PMC
March 2021

A chromosome-level genome assembly of rice leaffolder, Cnaphalocrocis medinalis.

Mol Ecol Resour 2021 Feb 3;21(2):561-572. Epub 2020 Nov 3.

State Key Laboratory of Rice Biology & Ministry of Agricultural and Rural Affairs, Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Institute of Insect Sciences, Zhejiang University, Hangzhou, China.

The rice leaffolder, Cnaphalocrocis medinalis Guenée (Crambidae, Lepidoptera), is an important agricultural pest that causes serious losses to rice production in rice-growing regions with high humidity and temperature. However, a lack of genomic resources limits in-depth understanding of its biological characteristics and ecological adaptation. Here, we sequenced the genome of rice leaffolder using the Illumina and PacBio platforms, yielding a genome assembly of 528.3 Mb with a contig N50 of 524.6 kb. A high percentage (96.4%) of Benchmarking Universal Single-Copy Orthologs (BUSCOs) were successfully detected, suggesting high-level completeness of the genome assembly. In total, 39.5% of the genome consists of repeat sequences and 15,045 protein-coding genes were annotated. Comparative phylogenomic analysis showed that some gene families associated with hormone biosynthesis expanded in rice leaffolder. Next, we used the Hi-C technique to produce a chromosome-level genome assembly with a scaffold N50 of 16.1 Mb by anchoring 3,248 scaffolds to 31 chromosomes. The rice leaffolder genome showed high chromosomal synteny with the genome of four other lepidopteran insects. By comparing coverage ratios from the genome resequencing of male and female pupae, we identified near intact Z and W chromosomes. The W chromosome is estimated as 20.75 Mb, which is the most complete known W chromosome in Lepidoptera. The protein-coding genes on the W chromosome were significantly enriched in metabolic pathways. In all, the high-quality genome assembly and the near-intact W chromosome of rice leaffolder should be a useful resource for the fields of insect migration, chromosome evolution and pest control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1755-0998.13274DOI Listing
February 2021

Cancer stemness of CD10-positive cells regulated by Hedgehog pathway promotes the resistance to cisplatin in oral squamous cell carcinoma.

Oral Dis 2020 Oct 9. Epub 2020 Oct 9.

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.

Objective: To explore the role of CD10 in cisplatin resistance of oral squamous cell carcinoma (OSCC) and its association with the Hedgehog (Hh) signaling pathway and cancer stem cells (CSCs).

Methods: The correlation between cell viability and CD10 expression was analyzed in different OSCC cell lines after the cisplatin treatment. Genes related to chemotherapy resistance, cancer stem cells and the epithelial-mesenchymal transition were detected by quantitative real-time PCR (qPCR) in CD10 and CD10 OSCC cells. Mouse xenograft model and venous metastasis model were used to explore the potential regulatory mechanism of the resistance effect of CD10 on cisplatin.

Results: The higher expression of CD10 gene in different cell lines displayed enhanced cisplatin resistance ability. The expression of genes related to chemotherapy resistance, cell stemness, and the epithelial-mesenchymal transition was significantly higher in CD10 cells compared with CD10 cells. Moreover, the combination of cisplatin and Hh pathway inhibitors significantly reduced the resistance of CD10 to cisplatin in the xenograft model and venous metastasis models.

Conclusion: CD10-positive cells are implicated in developing cisplatin resistance of OSCC, which could be related to its cancer stem cell characteristics regulated by the Hedgehog pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13673DOI Listing
October 2020

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 CD8 T cell abundance.

Oncoimmunology 2020 08 28;9(1):1810489. Epub 2020 Aug 28.

Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Bladder cancer is the ninth most frequent-diagnosed disease worldwide, bearing high morbidity and mortality rates. Studies have shown that a particular population of CXCR5CD8 T cells was associated with superior prognosis in various tumor types, and yet its role in muscle-invasive bladder cancer (MIBC) remains unclear. In this study, 662 MIBC patients from 3 cohorts (Zhongshan Hospital, = 141; Shanghai Cancer Center, = 108; The Cancer Genome Atlas, = 403) were analyzed retrospectively. 11 fresh resected samples of MIBC were examined to characterize the phenotype of CXCR5CD8 T cells and 402 MIBC patients from TCGA were applied for bioinformatics analysis. It was explored that the abundance of intratumoral CXCR5CD8 T cells indicated superior overall survival and disease-free survival. Patients with a higher infiltration of CXCR5CD8 T cells in tumor tissue benefit more from adjuvant chemotherapy (ACT). Intratumoral CXCR5CD8 T cells displayed cytolytic and self-renewal features. Remarkably, CXCR5CD8 T cells were mainly presented in the basal and stromal-rich subtypes of MIBC and tumors with enriched CXCR5CD8 T cells showed limited FGFR3 signaling signature and activated immunotherapeutic and EGFR associated pathway. In conclusion, we identified an excellent prognosis and ACT sensitive subtype of MIBC with intratumoral CXCR5CD8 T cell abundance. Tumors with high density of CXCR5CD8 T cells possessed potential sensitivity to immunotherapy and EGFR-targeted therapy. CXCR5CD8 T cells provide a new potential biomarker as well as a therapeutic target in MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1810489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470185PMC
August 2020

Intratumoral CCR5 neutrophils identify immunogenic subtype muscle-invasive bladder cancer with favorable prognosis and therapeutic responses.

Oncoimmunology 2020 08 12;9(1):1802176. Epub 2020 Aug 12.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Our previous studies revealed tumor-infiltrating neutrophils (TINs) played dichotomous roles in different cancers, indicating diverse TINs subtypes might orchestrate anti-tumor immunity or immune evasion, respectively. This study aimed to investigate the clinical significance and immune characteristics of CCR5TINs in muscle-invasive bladder cancer (MIBC). Two hundred and fifty-seven MIBC patients from two clinical centers and 95 fresh MIBC samples were included. CCR5TINs were stained by immunohistochemistry, and the relationship between patients' clinic-pathological features and prognosis was evaluated, respectively. Immunohistochemistry and flow cytometry were applied to assess the immune features of CCR5TINs and their correlations with other immune cells. In vitro study was conducted to estimate immune characteristics of CCR5TINs and their predictive potential for pembrolizumab therapeutic response. In the two MIBC cohorts, we found that high CCR5TINs infiltration could predict better overall survival (OS, = .032, 0.039) and recurrence-free survival (RFS, = .001, 0.006) and be associated with survival benefit from adjuvant chemotherapy (ACT, < .001 for OS and = .022 for RFS, respectively) in merely pT2N0 MIBC. Maraviroc could partly reduce IFN-γ secretion by CCR5TINs (< .001). CCR5TINs correlated with higher expression of effector molecules within CD8T cells. Notably, pembrolizumab treatment could only elevate the apoptosis status of tumor cells in the CCR5TINs high subgroup (.001), other than CCR5TINs low subgroup (= .481). Our results indicate that CCR5TINs could prime anti-tumor immune response through autonomous IFN-γ release, thus leading to favorable prognosis and superior therapeutic response to ACT and immunotherapy in MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1802176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458657PMC
August 2020

Ligand-modulated aqueous synthesis of color-tunable copper nanoclusters for the photoluminescent assay of Hg(II).

Mikrochim Acta 2020 09 4;187(10):545. Epub 2020 Sep 4.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Shandong Key Laboratory of Biochemical Analysis, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.

Water-soluble Cu nanoclusters (NCs) with tunable emission were synthesized through an eco-friendly one-pot aqueous method. Blue-, green-, and red-emitting NCs with the emission peaks at 420 nm, 505 nm, and 630 nm were obtained by employing ethanediamine, cysteine, and glutathione as surface ligands, respectively. The ligand effects on the optical properties of Cu NCs were studied by the single variable method. It has been revealed by systematic characterizations that the dependence of emission color on the structures of ligands was mainly attributed to their different size-tuning effects. Glutathione has the strongest chelating ability and it can significantly reduce the monomer reactivity and thus decrease the supersaturation degree of the reaction, which is favorable for modulating Cu precursor to grow into larger NCs. In contrast, ethanediamine ligand resulted in smaller nanoclusters due to its weaker binding capability. Because of the strong emission and terrific fluorescent stability, Cu NCs capped with ethanediamine, possessing an emission peak at 420 nm when excited at a wavelength of 350 nm, were directly used for probing Hg(II) with satisfying selectivity, presenting a linear range of 0.1-5.0 mM and a detection limit of 33 μM. The sensor showed good performance in real sample analysis with recoveries ranging from 99% to 103%, and comparable accuracy with atomic fluorescence spectroscopy, manifesting the reliability of the current strategy for sensing Hg(II). Graphical abstract Water-soluble copper nanoclusters with blue, green, and red emissions were synthesized by employing ethanediamine, cysteine, and glutathione as surface ligands respectively, and the blue-emitting nanoclusters with strong emission and terrific stability were directly used for selectively sensing Hg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00604-020-04539-6DOI Listing
September 2020

PPARγ enhanced Adiponectin polymerization and trafficking by promoting RUVBL2 expression during adipogenic differentiation.

Gene 2021 Jan 30;764:145100. Epub 2020 Aug 30.

College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:

Adipocyte differentiation is an essential part of adipose tissue development, and is closely related to obesity and obesity-related diseases. In this study, we found that the expression of PPARγ, RUVBL2 and Adiponectin were concurrently obviously increased in the 5th-7th day of 3T3-L1 cell differentiation. PPARγ overexpression or the PPARγ activator facilitated Adiponectin trafficking and secretion and upregulated RUVBL2 expression as well as AS160 phosphorylation during adipogenic differentiation of 3T3-L1 cells. Consistently RUVBL2 overexpression also enhanced the polymerization and secretion of Adiponectin, in contrast, RUVBL2 knockdown reduced Adiponectin secretion. Further, PPARγ significantly enhanced RUVBL2 promoter activity and transcription. The progressive deletions and mutations of RUVBL2 promoter for PPARγ binding sites suggested that the PPARγ binding motif situated at -804/-781 bp is an essential component required for RUVBL2 promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that PPARγ can directly interact with the RUVBL2 promoter DNA. Taken together, these data suggest that PPARγ promotes the expression, polymerization and secretion of Adiponectin by activating RUVBL2 transcriptionally, which accelerates 3T3-L1 cell differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2020.145100DOI Listing
January 2021

Intratumoral TIGIT CD8 T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer.

J Immunother Cancer 2020 08;8(2)

Department of Immunology, Fudan University School of Basic Medical Sciences, Shanghai, China

Background: T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT CD8 T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC).

Methods: 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT CD8 T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry.

Results: High infiltration of intratumoral TIGIT CD8 T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT CD8 cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT CD8 T-cell abundance was correlated with impaired CD8 T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT CD8 T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils.

Conclusion: Intratumoral TIGIT CD8 T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT CD8 T-cell abundance correlated with dampened CD8 T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT CD8 T-cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-000978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430558PMC
August 2020

Oral administration of microencapsulated egg yolk immunoglobulin (IgY) in turbot (Scophthalmus maximus) to combat against Edwardsiella tarda 2CDM001 infections.

Fish Shellfish Immunol 2020 Nov 12;106:609-620. Epub 2020 Aug 12.

School of Bioengineering, Dalian University of Technology, Dalian, 116024, China; Center for Food Safety of Animal Origin, Ministry of Education, Dalian University of Technology, Dalian, 116600, China. Electronic address:

Edwardsiellosis, an extremely harmful disease can be caused by Edwardsiella tarda, severely restricts the development of turbot (Scophthalmus maximus) farming worldwide, especially in China. This study aimed to establish an effective and feasible prophylaxis by feeding chitosan-alginate coated egg yolk immunoglobulin (IgY) against E. tarda 2CDM001 infections in the process of turbot farming. Enzyme-linked immunosorbent assays proved that the obtained specific IgY could specifically target E. tarda 2CDM001 and five other E. tarda isolates (1a5p, Hz-s, 1a1s, fs-a1 and 58p8). In-vitro, the bacteriostatic effects of specific IgY showed dose dependencies at concentrations ranging from 1 to 10 mg/mL. Moreover, E. tarda 2CDM001 incubated with 10 mg/mL specific IgY could induce the destruction of cell wall structures and significantly decrease the bacterial surface hydrophobicity (p < 0.05). In this study, turbots were challenged with 10 CFU E. tarda 2CDM001 after seven days of continuous feeding with basal diets containing microencapsulated IgYs. Survival rates of the 5%, 3% and 1% microencapsulated specific IgY groups were 63.3%, 56.7% and 20% on the tenth day post infection, respectively, while the turbots in the positive control and non-specific IgY groups all died within ten days. Oral administration of basal diets containing 5% microencapsulated specific IgY significantly reduced IL-1β, IL-8, TNF-α and C3 transcript levels in the head kidney and spleen of turbots compared with the positive and non-specific IgY groups at 24 h after E. tarda 2CDM001 challenging (p < 0.05). Pathological increase of leukocytes in the specific IgY group was significantly lower than that in the positive control and non-specific IgY groups (p < 0.05), decreasing slowly after 24 h of infection and showing a recovery trend. Erythrocyte counts and hemoglobin concentrations of turbots in positive and non-specific IgY groups showed a marked decrease compared with the negative and specific groups at 96 h after E. tarda 2CDM001 infection (p < 0.05). These results suggest that passive immunity via feeding microencapsulated specific IgY could be used as a valuable preventative in turbot against E. tarda 2CDM001 infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2020.08.024DOI Listing
November 2020

Chromosomal-level genomes of three rice planthoppers provide new insights into sex chromosome evolution.

Mol Ecol Resour 2021 Jan 18;21(1):226-237. Epub 2020 Nov 18.

State Key Laboratory of Rice Biology & Ministry of Agricultural and Rural Affairs Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Institute of Insect Sciences, Zhejiang University, Hangzhou, China.

The brown planthopper Nilaparvata lugens, white-backed planthopper Sogatella furcifera, and small brown planthopper Laodelphax striatellus are three major insect pests of rice. They are genetically close; however, they differ in several ecological traits such as host range, migration capacity, and in their sex chromosomes. Though the draft genome of these three planthoppers have been previously released, the quality of genome assemblies need to be improved. The absence of chromosome-level genome resources has hindered in-depth research of these three species. Here, we performed a de novo genome assembly for N. lugens to increase its genome assembly quality with PacBio and Illumina platforms, increasing the contig N50 to 589.46 Kb. Then, with the new N. lugens genome and previously reported S. furcifera and L. striatellus genome assemblies, we generated chromosome-level scaffold assemblies of these three planthopper species using HiC scaffolding technique. The scaffold N50s significantly increased to 77.63 Mb, 43.36 Mb and 29.24 Mb for N. lugens, S. furcifera and L. striatellus, respectively. To identify sex chromosomes of these three planthopper species, we carried out genome re-sequencing of males and females and successfully determined the X and Y chromosomes for N. lugens, and X chromosome for S. furcifera and L. striatellus. The gene content of the sex chromosomes showed high diversity among these three planthoppers suggesting the rapid evolution of sex-linked genes, and all chromosomes showed high synteny. The chromosome-level genome assemblies of three planthoppers would provide a valuable resource for a broad range of future research in molecular ecology, and subsequently benefits development of modern pest control strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1755-0998.13242DOI Listing
January 2021

Poor clinical outcomes and immunoevasive contexture in interleukin-9 abundant muscle-invasive bladder cancer.

Int J Cancer 2020 12 20;147(12):3539-3549. Epub 2020 Aug 20.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Chemotherapy and immunotherapy yield survival benefits for muscle-invasive bladder cancer (MIBC) patients, in which tumor microenvironment has been found to exert crucial roles through tipping the balance between antitumor immunity and immune evasion. Our study aims to explore the clinical significance and therapeutic role of intratumoral interleukin-9-producing cells (IL-9 cells) in MIBC. Two hundred fifty-nine MIBC patients from two independent clinic centers were utilized for retrospective analysis in the study. Sixty-five fresh MIBC tumor tissues were used to evaluate the infiltration and function of immune cells via flow cytometry and ex vivo intervention experiments. Three hundred ninety-one MIBC patients of The Cancer Genome Atlas were applied for bioinformatics analysis. It was found that patients with high IL-9 cells infiltration had worse overall survival and relapse-free survival. pT2 patients with low IL-9 cells infiltration could benefit more from adjuvant chemotherapy (ACT). IL-9 cells infiltration was correlated with decreased expression of granzyme B from CD8 T cells and natural killer (NK) cells and perforin from CD8 T cells, while blockade of IL-9 reactivated the antitumor capacity of both cells leading to tumor regression. Furthermore, IL-9 cells infiltration could be a biomarker for predicting anti-PD-1 efficacy. In conclusion, IL-9 cells infiltration could be applied as an independent prognosticator for clinical outcome and ACT/anti-PD-1 effectiveness. IL-9 cells infiltration diminished the cytotoxicity of CD8 T cells and NK cells resulting in tumor immune evasion, and thus targeting IL-9 could be a potential therapeutic strategy for MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33237DOI Listing
December 2020

Rational Manipulation of Stacking Arrangements in Three-Dimensional Zeolites Built from Two-Dimensional Zeolitic Nanosheets.

Angew Chem Int Ed Engl 2020 Nov 31;59(45):19934-19939. Epub 2020 Aug 31.

Department of Chemical System Engineering, The University of Tokyo, Tokyo, 113-8656, Japan.

Unit-cell-thin zeolitic nanosheets have emerged as fascinating materials for catalysis and separation. The controllability of nanosheet stacking is extremely challenging in the chemistry of two-dimensional zeolitic materials. To date, the organization of zeolitic nanosheets in hydrothermal synthesis has been limited by the lack of tunable control over the guest-host interactions between organic structure-directing agents (OSDAs) and zeolitic nanosheets. A direct synthetic methodology is reported that enables systematic manipulation of the aluminosilicate MWW-type nanosheet stacking. Variable control of guest-host interactions is rationally achieved by synergistically altering the charge density of OSDAs and synthetic silica-to-alumina composition. These finely controlled interactions allow successful preparation of a series of three-dimensional (3D) zeolites, with MWW-layer stacking in wide ranges from variably disorder to fully ordered, leading to tunable catalytic activity in the cracking reaction. These results highlight unprecedented opportunities to modulate zeolitic nanosheets arrangement in 3D zeolites whose structure can be tailored for catalysis and separation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202009336DOI Listing
November 2020

Suppression of G6PD induces the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin to block epithelial-mesenchymal transition and lymphatic metastasis.

Br J Cancer 2020 10 28;123(8):1315-1325. Epub 2020 Jul 28.

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 100081, Beijing, China.

Background: As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear.

Methods: G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and lectin blot, mass spectrometer analysis, ChIP-PCR, and luciferase reporter assay. BALB/c-nude mice were used to establish orthotopic xenograft model.

Results: G6PD expression in the tumours of 105 OSCC patients was associated with lymphatic metastasis and prognosis. In vitro cellular study suggested that G6PD suppression impaired cell migration, invasion, and epithelial-mesenchymal transition. Furtherly, G6PD knockdown activated the JNK pathway, which then blocked the AKT/GSK-3β/Snail axis to induce E-Cadherin expression and transcriptionally regulated MGAT3 expression to promote bisecting GlcNAc-branched N-glycosylation of E-Cadherin. An orthotopic xenograft model further confirmed that dehydroepiandrosterone reduced lymphatic metastatic rate of OSCC, which was partially reversed by JNK inhibition.

Conclusions: Suppression of G6PD promoted the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin via activating the JNK pathway, which thus acted on OSCC metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-1007-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555552PMC
October 2020