Publications by authors named "Zeyu Yang"

88 Publications

Rapid Spread of Severe Fever with Thrombocytopenia Syndrome Virus by Parthenogenetic Asian Longhorned Ticks.

Emerg Infect Dis 2022 Feb;28(2):363-372

Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. This virus is transmitted by the Asian longhorned tick (Haemaphysalis longicornis), which has parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in ≥15 provinces in China and strongly correlated with the distribution of severe fever with thrombocytopenia syndrome cases. However, distribution of these cases was poorly correlated with the distribution of populations of bisexual ticks. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ticks was collected from migratory birds captured at an SFTSV-endemic area, implicating the contribution to the long-range movement of these ticks in China. The SFTSV susceptibility of parthenogenetic females was similar to that of bisexual females under laboratory conditions. These results suggest that parthenogenetic Asian longhorned ticks, probably transported by migratory birds, play a major role in the rapid spread of SFTSV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2802.211532DOI Listing
February 2022

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial.

Mol Cancer 2022 01 3;21(1). Epub 2022 Jan 3.

Genecast Biotechnology Co., Ltd., Wuxi City, China.

Background: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown.

Methods: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values.

Results: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy.

Conclusion: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC.

Trial Registration: ClinicalTrials.gov identifier: NCT03668496.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-021-01479-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722280PMC
January 2022

miR395-regulated sulfate metabolism exploits pathogen sensitivity to sulfate to boost immunity in rice.

Mol Plant 2021 Dec 28. Epub 2021 Dec 28.

National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

MicroRNAs (miRNAs) play important roles in plant physiological activities. However, their roles and molecular mechanisms in boosting plant immunity, especially through the modulation of macronutrient metabolism in response to pathogens, are largely unknown. Here, we report that an evolutionarily conserved miRNA, miR395, promotes resistance to Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), two destructive bacterial pathogens, by regulating sulfate accumulation and distribution in rice. Specifically, miR395 targets and suppresses the expression of the ATP sulfurylase gene OsAPS1, which functions in sulfate assimilation, and two sulfate transporter genes, OsSULTR2;1 and OsSULTR2;2, which function in sulfate translocation, to promote sulfate accumulation, resulting in broad-spectrum resistance to bacterial pathogens in miR395-overexpressing plants. Genetic analysis revealed that miR395-triggered resistance is involved in both pathogen-associated molecular pattern-triggered immunity and R gene-mediated resistance. Moreover, we found that accumulated sulfate but not S-metabolites inhibits proliferation of pathogenic bacteria, revealing a sulfate-mediated antibacterial defense mechanism that differs from sulfur-induced resistance. Furthermore, compared with other bacteria, Xoo and Xoc, which lack the sulfate transporter CysZ, are sensitive to high levels of extracellular sulfate. Accordingly, miR395-regulated sulfate accumulation impaired the virulence of Xoo and Xoc by decreasing extracellular polysaccharide production and biofilm formation. Taken together, these results suggest that rice miR395 modulates sulfate metabolism to exploit pathogen sensitivity to sulfate and thereby promotes broad-spectrum resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molp.2021.12.013DOI Listing
December 2021

Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous non-small-cell lung cancer (CameL-sq): a phase 3 trial.

J Thorac Oncol 2021 Dec 16. Epub 2021 Dec 16.

Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China.

Introduction: Camrelizumab, a humanized IgG4-κ monoclonal antibody against PD-1, has demonstrated anti-tumor activity and tolerability across various tumors, including lung cancers. We conducted this double-blind, randomized phase 3 trial to investigate the efficacy and safety of camrelizumab or placebo plus chemotherapy as first-line treatment for patients with advanced squamous non-small-cell lung cancer (NSCLC). The predictive value of circulating tumor DNA (ctDNA) dynamics was also analyzed.

Methods: CameL-sq, a double-blind, randomized phase 3 trial (NCT03668496), was conducted in 53 centers in China. 389 patients with stage IIIB-IV squamous NSCLC were randomized (1:1) to receive 4-6 cycles of carboplatin plus paclitaxel with camrelizumab or placebo (q3w), followed by maintenance therapy with camrelizumab or placebo. Peripheral blood ctDNA samples were collected at the baseline and the time after two cycles of treatment.

Results: Of 389 eligible patients, 193 patients allocated camrelizumab plus chemotherapy and 196 patients allocated placebo plus chemotherapy were included in the efficacy and safety analysis. The results showed significantly prolonged progression-free survival (PFS, median, 8·5 vs 4.9 months; p<0.0001) and overall survival (OS, median, not reached vs 14.5 months; p<0.0001) with camrelizumab-chemotherapy versus placebo-chemotherapy. No unexpected treatment/immune-related adverse events were observed in both two groups. Biomarker analysis revealed that ctDNA clearance after two cycles treatment was independently associated with dramatically longer PFS (p<0.0001) and OS (p<0.0001) in camrelizumab plus chemotherapy group.

Conclusions: Our findings support camrelizumab plus chemotherapy as a first-line treatment option in advanced squamous NSCLC. On-treatment ctDNA dynamics showed the potent to predict the efficacy of camrelizumab plus chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2021.11.018DOI Listing
December 2021

Process Development for Newcastle Disease Virus-Vectored Vaccines in Serum-Free Vero Cell Suspension Cultures.

Vaccines (Basel) 2021 Nov 16;9(11). Epub 2021 Nov 16.

Viral Vectors and Vaccines Bioprocessing Group, Department of Bioengineering, McGill University, Montreal, QC H3A 0G4, Canada.

The ongoing COVID-19 pandemic drew global attention to infectious diseases, attracting numerous resources for development of pandemic preparedness plans and vaccine platforms-technologies with robust manufacturing processes that can quickly be pivoted to target emerging diseases. Newcastle Disease Virus (NDV) has been studied as a viral vector for human and veterinary vaccines, but its production relies heavily on embryonated chicken eggs, with very few studies producing NDV in cell culture. Here, NDV is produced in suspension Vero cells, and analytical assays (TCID and ddPCR) are developed to quantify infectious and total viral titer. NDV-GFP and NDV-FLS (SARS-CoV-2 full-length spike protein) constructs were adapted to replicate in Vero and HEK293 suspension cultures using serum-free media, while fine-tuning parameters such as MOI, temperature, and trypsin concentration. Shake flask productions with Vero cells resulted in infectious titers of 1.07 × 10 TCID/mL for NDV-GFP and 1.33 × 10 TCID/mL for NDV-FLS. Production in 1 L batch bioreactors also resulted in high titers in culture supernatants, reaching 2.37 × 10 TCID/mL for NDV-GFP and 3.16 × 10 TCID/mL for NDV-FLS. This shows effective NDV production in cell culture, building the basis for a scalable vectored-vaccine manufacturing process that can be applied to different targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines9111335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623276PMC
November 2021

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

Intrinsic Antibacterial and Conductive Hydrogels Based on the Distinct Bactericidal Effect of Polyaniline for Infected Chronic Wound Healing.

ACS Appl Mater Interfaces 2021 Oct 28. Epub 2021 Oct 28.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

Most chronic wounds suffer from infections, and their treatment is challenging. The usage of antibiotics may lead to bacterial resistance and adverse side effects. Positively charged substances have shown promise, but their applications are usually limited by certain cytotoxicity or complex synthesis. Doped polyaniline that carries a high density of positive charges would be a promising candidate due to its good biocompatibility and easy availability, but its interaction with bacteria has not been elucidated. Herein, the distinct bactericidal effect of polyaniline against Gram-positive bacteria has been verified. The antibacterial activity may result from the specific interaction with lipoteichoic acid to destroy the Gram-positive bacterial cell wall. Polyaniline and a macromolecular dopant (sulfonated hyaluronic acid) are used to construct a flexible hydrogel with skin-mimic electrical conductivity. The in vivo results demonstrate that electrical stimulation (ES) through this hydrogel is superior to ES via separated electrodes (the ES strategy used clinically) for promoting infected chronic wound healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c14088DOI Listing
October 2021

Occurrence, characterization, source, and risk assessment of petroleum-related hydrocarbons in sediments along St. Clair River, Ontario, Canada.

Mar Pollut Bull 2021 Dec 18;173(Pt B):113037. Epub 2021 Oct 18.

Emergencies Science and Technology Section (ESTS), Environment & Climate Change Canada, Ottawa, ON, Canada.

Total petroleum hydrocarbons (TPH), n-alkanes, petroleum biomarkers, and polycyclic aromatic hydrocarbons (PAHs) were analyzed in the sediments collected from the shorelines and bottom of St. Clair River, Ontario, Canada. Most of the sampling sites had low TPH (< 20 μg/g). River bottom sediment usually had higher level of TPHs, total alkanes, total biomarkers, and total PAHs than most of the shoreline ones. Mixed biogenic and petrogenic n-alkanes were present in all the sites. Most sites had trace amounts of petroleum biomarkers. Mixed pyrogenic and petrogenic inputs with the predominant petroleum, have contributed to the detected PAHs at all sampling sites. PAHs detected would not show potential toxicity to benthic organisms in all shoreline sampling sites; however, some light molecular weight PAHs (e.g., phenanthrene, 2-methyl naphthalene, and acenaphthylene) are anticipated to have possible adverse impacts to sediment-dwelling organisms in part of the river bottom sediment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2021.113037DOI Listing
December 2021

Construction of a 5-feature gene model by support vector machine for classifying osteoporosis samples.

Bioengineered 2021 12;12(1):6821-6830

Department of Orthopedics, Ruijin Hospital LuWan Branch, School of Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Osteoporosis is a progressive bone disease in the elderly and lacks an effective classification method of patients. This study constructed a gene signature for an accurate prediction and classification of osteoporosis patients. Three gene expression datasets of osteoporosis samples were acquired from the Gene Expression Omnibus database with pre-set criteria. Differentially expressed genes (DEGs) between normal and diseased osteoporosis samples were screened using Limma package in R language. Protein-protein interaction (PPI) network was established based on interaction data of the DEGs from the Human Protein Reference Database. Classification accuracy of the classifier was assessed with sensitivity, specificity and area under curve (AUC) using the pROC package in the R. Pathway enrichment analysis was performed on feature genes with clusterProfiler. A total of 310 differentially expressed genes between two samples were associated with positive regulation of protein secretion and cytokine secretion, neutrophil-mediated immunity, and neutrophil activation. PPI network of DEGs consisted of 12 genes. A SVM classifier based on five feature genes was developed to classify osteoporosis samples, showing a higher prediction accuracy and AUC for GSE35959, GSE62402, GSE13850, GSE56814, GSE56815 and GSE7429 datasets. A SVM classifier with a high accuracy was developed for predicting osteoporosis. The genes included may be the potential feature genes in osteoporosis development.DEGs: Differentially expressed genes; PPI: protein-protein interaction; WHO: World Health Organization; SVM: Support vector machine; GEO: Gene Expression Omnibus; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; BP: Biological Process; CC: Cellular Component; MF: Molecular Function; SVM: Support vector machines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21655979.2021.1971026DOI Listing
December 2021

Conductive dual hydrogen bonding hydrogels for the electrical stimulation of infected chronic wounds.

J Mater Chem B 2021 10 6;9(38):8138-8146. Epub 2021 Oct 6.

National Engineering Research Center for Biomaterials, Sichuan University, 29 Wang Jiang Road, Chengdu, Sichuan, 610065, China.

Electrical stimulation (ES) rigid electrodes near the wound is one of the promising approaches for chronic wound treatment, but it is unable to stimulate the whole wound area and treat infected wounds. In this study, a tough conductive hydrogel was prepared by the copolymerization of -acryloyl glycinamide (NAGA) with quaternized chitosan--polyaniline (QCSP). The hydrogel showed a similar conductivity to the human skin and robust mechanical properties due to the dual hydrogen bonding motifs. The grafted polyaniline segments and functionalized quaternary ammonium groups showed intense antimicrobial activity against and biofilms. The assay in diabetic rats proves that the ES the conductive hydrogel was more effective in promoting the healing of infected wounds than the conventional ES rigid electrodes. Due to the excellent flexibility and antibacterial properties, this conductive hydrogel shows great promise for infected chronic wound treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb01432cDOI Listing
October 2021

Validation of low-coverage whole-genome sequencing for mitochondrial DNA variants suggests mitochondrial DNA as a genetic cause of preterm birth.

Hum Mutat 2021 12 8;42(12):1602-1614. Epub 2021 Sep 8.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Preterm birth (PTB), or birth that occurs earlier than 37 weeks of gestational age, is a major contributor to infant mortality and neonatal hospitalization. Mutations in the mitochondrial genome (mtDNA) have been linked to various rare mitochondrial disorders and may be a contributing factor in PTB given that maternal genetic factors have been strongly linked to PTB. However, to date, no study has found a conclusive connection between a particular mtDNA variant and PTB. Given the high mtDNA copy number per cell, an automated pipeline was developed for detecting mtDNA variants using low-coverage whole-genome sequencing (lcWGS) data. The pipeline was first validated against samples of known heteroplasmy, and then applied to 929 samples from a PTB cohort from diverse ethnic backgrounds with an average gestational age of 27.18 weeks (range: 21-30). Our new pipeline successfully identified haplogroups and a large number of mtDNA variants in this large PTB cohort, including 8 samples carrying known pathogenic variants and 47 samples carrying rare mtDNA variants. These results confirm that lcWGS can be utilized to reliably identify mtDNA variants. These mtDNA variants may make a contribution toward preterm birth in a small proportion of live births.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.24279DOI Listing
December 2021

PAM-DenseNet: A Deep Convolutional Neural Network for Computer-Aided COVID-19 Diagnosis.

IEEE Trans Cybern 2021 Aug 24;PP. Epub 2021 Aug 24.

Currently, several convolutional neural network (CNN)-based methods have been proposed for computer-aided COVID-19 diagnosis based on lung computed tomography (CT) scans. However, the lesions of pneumonia in CT scans have wide variations in appearances, sizes, and locations in the lung regions, and the manifestations of COVID-19 in CT scans are also similar to other types of viral pneumonia, which hinders the further improvement of CNN-based methods. Delineating infection regions manually is a solution to this issue, while excessive workload of physicians during the epidemic makes it difficult for manual delineation. In this article, we propose a CNN called dense connectivity network with parallel attention module (PAM-DenseNet), which can perform well on coarse labels without manually delineated infection regions. The parallel attention module automatically learns to strengthen informative features from both channelwise and spatialwise simultaneously, which can make the network pay more attention to the infection regions without any manual delineation. The dense connectivity structure performs feature maps reuse by introducing direct connections from previous layers to all subsequent layers, which can extract representative features from fewer CT slices. The proposed network is first trained on 3530 lung CT slices selected from 382 COVID-19 lung CT scans, 372 lung CT scans infected by other pneumonia, and 200 normal lung CT scans to obtain a pretrained model for slicewise prediction. We then apply this pretrained model to a CT scans dataset containing 94 COVID-19 CT scans, 93 other pneumonia CT scans, and 93 normal lung scans, and achieve patientwise prediction through a voting mechanism. The experimental results show that the proposed network achieves promising results with an accuracy of 94.29%, a precision of 93.75%, a sensitivity of 95.74%, and a specificity of 96.77%, which is comparable to the methods that are based on manually delineated infection regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2020.3042837DOI Listing
August 2021

Pharmaceutical targeting of succinate dehydrogenase in fibroblasts controls bleomycin-induced lung fibrosis.

Redox Biol 2021 10 26;46:102082. Epub 2021 Jul 26.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix in the lung with fibroblast-to-myofibroblast transition, leading to chronically compromising lung function and death. However, very little is known about the metabolic alterations of fibroblasts in IPF, and there is still a lack of pharmaceutical agents to target the metabolic dysregulation. Here we show a glycolysis upregulation and fatty acid oxidation (FAO) downregulation in fibroblasts from fibrotic lung, and perturbation of glycolysis and FAO affects fibroblasts transdifferentiation. In addition, there is a significant accumulation of succinate both in fibrotic lung tissues and myofibroblasts, where succinate dehydrogenase (SDH) operates in reverse by reducing fumarate to succinate. Then succinate contributes to glycolysis upregulation and FAO downregulation by stabilizing HIF-1α, which promotes the development of lung fibrosis. In addition, we identify a near-infrared small molecule dye, IR-780, as a targeting agent which stimulates mild inhibition of succinate dehydrogenase subunit A (SDHA) in fibroblasts, and which inhibits TGF-β1 induced SDH and succinate elevation, then to prevent fibrosis formation and respiratory dysfunction. Further, enhanced cell retention of IR-780 is shown to promote severe inhibition of SDHA in myofibroblasts, which may contribute to excessive ROS generation and selectively induces myofibroblasts to apoptosis, and then therapeutically improves established lung fibrosis in vivo. These findings indicate that targeting metabolic dysregulation has significant implications for therapies aimed at lung fibrosis and succinate dehydrogenase is an exciting new therapeutic target to treat IPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2021.102082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342973PMC
October 2021

The rice Raf-like MAPKKK OsILA1 confers broad-spectrum resistance to bacterial blight by suppressing the OsMAPKK4-OsMAPK6 cascade.

J Integr Plant Biol 2021 Oct 6;63(10):1815-1842. Epub 2021 Aug 6.

National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan, 430070, China.

Mitogen-activated protein kinase kinase kinase (MAPKKK) are the first components of MAPK cascades, which play pivotal roles in signaling during plant development and physiological processes. The genome of rice encodes 75 MAPKKKs, of which 43 are Raf-like MAPKKKs. The functions and action modes of most of the Raf-like MAPKKKs, whether they function as bona fide MAPKKKs and which are their downstream MAPKKs, are largely unknown. Here, we identified the osmapkkk43 mutant, which conferred broad-spectrum resistance to Xanthomonas oryzae pv. oryzae (Xoo), the destructive bacterial pathogen of rice. Oryza sativa (Os)MAPKKK43 encoding a Raf-like MAPKKK was previously known as Increased Leaf Angle 1 (OsILA1). Genetic analysis indicated that OsILA1 functioned as a negative regulator and acted upstream of the OsMAPKK4-OsMAPK6 cascade in rice-Xoo interactions. Unlike classical MAPKKKs, OsILA1 mainly phosphorylated the threonine 34 site at the N-terminal domain of OsMAPKK4, which possibly influenced the stability of OsMAPKK4. The N-terminal domain of OsILA1 is required for its homodimer formation and its full phosphorylation capacity. Taken together, our findings reveal that OsILA1 acts as a negative regulator of the OsMAPKK4-OsMAPK6 cascade and is involved in rice-Xoo interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jipb.13150DOI Listing
October 2021

Occurrence, characterization, and ecological assessment of petroleum-related hydrocarbons on the shoreline of Fraser River Delta, British Columbia, Canada.

Mar Pollut Bull 2021 Sep 1;170:112668. Epub 2021 Jul 1.

Emergencies Science and Technology Section (ESTS), Environment & Climate Change Canada, Ottawa, ON, Canada.

The Fraser River Delta is a unique and dynamic region supporting the diverse ecosystems and habitats in the Canadian West Coast. Total petroleum hydrocarbons (TPH), n-alkanes, petroleum biomarkers, and polycyclic aromatic hydrocarbons (PAHs) were analyzed for the intertidal sediments taken from the shorelines of the Delta area, British Columbia, Canada, to establish the baseline background data. Most of the sampling sites had low TPH (< 40 μg/g); only two samples had TPH from 100 to 150 μg/g. Mainly biogenic n-alkanes were present in all sites. Non-detectable to trace amounts of petroleum biomarkers were found at most sites. Mixed pyrogenic and petrogenic inputs contributed to the presence of PAHs at most sites. PAHs are not present in amounts anticipated negative effects to benthic organisms in all sampling sites, except that benzo (a) pyrene (BaP) from the upper intertidal zone (UIZ) of Burnaby Fraser Foreshore Park may have possible adverse biological effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2021.112668DOI Listing
September 2021

Simulating diluted bitumen spills in boreal lake limnocorrals - Part 1: Experimental design and responses of hydrocarbons, metals, and water quality parameters.

Sci Total Environ 2021 Oct 23;790:148537. Epub 2021 Jun 23.

Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Electronic address:

Large-scale, in-lake enclosures (limnocorrals) were used to simulate spills of diluted bitumen (dilbit) in a boreal lake. In this study we use these simulated spills, which covered a range of sizes (oil:water ratio) representative of the upper 25% of onshore crude oil spills in North America (2008-2019), to assess the fate of dilbit-derived hydrocarbons and metals as well as the impacts of the spills on standard water quality parameters. The systems were monitored over 70 days following the application of dilbit amounts ranging between 1.5 and 179.8 L into 10-m diameter, ~100 m limnocorrals. The concentration of total petroleum hydrocarbons (TPH) in the water column increased rapidly over the first two weeks reaching a plateau that ranged between 200 μg/L and 2200 μg/L for the lowest and highest treatment respectively. The concentration of total polycyclic aromatic compounds (PACs) also increased over the first two weeks, prior to a slow decrease until day 70. The maximum measured concentrations in the highest treatment were 2858 ng/L for the sum of all 46 quantified PACs, 2716 ng/L for alkylated PACs and 154 ng/L for the 16 EPA priority PAHs. The concentrations of PACs in the sediment increased continuously over the study in the three highest treatments with maximum observed concentrations of 189 ng/g for ΣPAC, 169 ng/g for ΣPAC. No significant treatment-related changes in the 16 EPA priority PAHs were observed in the sediment. Of the 25 metals quantified in the water column, only manganese, molybdenum, and vanadium displayed a significant treatment effect with increases of 280, 76 and 25% respectively in the total fraction. These results can help us understand and predict the fate of oil-derived contaminants following a spill and characterize the exposure of freshwater organisms living within them. These results should help inform the risk assessment of future dilbit transportation projects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.148537DOI Listing
October 2021

Differentiation of cystic biliary atresia and choledochal cysts using prenatal ultrasonography.

Ultrasonography 2022 Jan 10;41(1):140-149. Epub 2021 May 10.

Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.

Purpose: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC).

Methods: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth.

Results: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971.

Conclusion: The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14366/usg.21028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696141PMC
January 2022

Diagnostic and prognostic value of tumor-infiltrating B cells in lymph node metastases of papillary thyroid carcinoma.

Virchows Arch 2021 Nov 19;479(5):947-959. Epub 2021 Jun 19.

Breast and Thyroid Surgical Department, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China.

Lymph node metastases are strongly associated with unfavorable prognosis in papillary thyroid carcinoma (PTC) patients. However, there are few sensitive or specific indicators that can diagnose or predict lymph node metastases in PTC. The objective of our study was to identify reliable indicators for the diagnosis and prediction of lymph node metastases of PTC. The PTC data set was obtained from The Cancer Genome Atlas (TCGA) cohort. Information on tumor-infiltrating immune cells in PTC was acquired using single-sample gene set enrichment analysis (ssGSEA). Then, the progression-free survival (PFS) rates of PTC patients were evaluated by Kaplan-Meier curves. A tissue microarray including 58 normal thyroid tissues and 57 PTC tissues was processed for CD19 immunohistochemistry staining. Finally, evaluation of phenotype permutations was performed using gene set enrichment analysis (GSEA). There was an appreciable association between immune infiltration and lymph node metastases in PTC. Among those immune cells, B cells and cytotoxic cells showed significant predictive accuracy for lymph node metastases in PTC. Tumor-infiltrating B cells and NK cells were associated with favorable prognosis, while tumor-associated NK CD56 cells were correlated with poor prognosis in PTC patients. IHC analyses of PTC further confirmed a notably negative correlation between B cell infiltration and lymph node metastases in PTC. Additionally, mutations in BRAF, a dominant cause of tumor mutation burden (TMB), were positively correlated with reduced B cell infiltration and lymph node metastases in PTC. GSEA revealed that epithelial-mesenchymal transition, IL-6/JAK/STAT3 signaling, the inflammatory response, and TNF-α signaling via the NFκB pathway were remarkably suppressed pathways in patients with BRAF mutations. Tumor-associated lymphocytic infiltration, especially B cell infiltration, provides diagnostic and prognostic value for lymph node metastases in PTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03137-yDOI Listing
November 2021

Hypomorphic and hypermorphic mouse models of Fsip2 indicate its dosage-dependent roles in sperm tail and acrosome formation.

Development 2021 06 14;148(11). Epub 2021 Jun 14.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China.

Loss-of-function mutations in multiple morphological abnormalities of the sperm flagella (MMAF)-associated genes lead to decreased sperm motility and impaired male fertility. As an MMAF gene, the function of fibrous sheath-interacting protein 2 (FSIP2) remains largely unknown. In this work, we identified a homozygous truncating mutation of FSIP2 in an infertile patient. Accordingly, we constructed a knock-in (KI) mouse model with this mutation. In parallel, we established an Fsip2 overexpression (OE) mouse model. Remarkably, KI mice presented with the typical MMAF phenotype, whereas OE mice showed no gross anomaly except for sperm tails with increased length. Single-cell RNA sequencing of the testes uncovered altered expression of genes related to sperm flagellum, acrosomal vesicle and spermatid development. We confirmed the expression of Fsip2 at the acrosome and the physical interaction of this gene with Acrv1, an acrosomal marker. Proteomic analysis of the testes revealed changes in proteins sited at the fibrous sheath, mitochondrial sheath and acrosomal vesicle. We also pinpointed the crucial motifs of Fsip2 that are evolutionarily conserved in species with internal fertilization. Thus, this work reveals the dosage-dependent roles of Fsip2 in sperm tail and acrosome formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.199216DOI Listing
June 2021

Maternal obesity accelerated non-alcoholic fatty liver disease in offspring mice by reducing autophagy.

Exp Ther Med 2021 Jul 3;22(1):716. Epub 2021 May 3.

Graduate School, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by an excessive accumulation of triacylglycerol in the liver. Autophagy is a lysosome-dependent degradation product recovery process, which widely occurs in eukaryotic cells, responsible for the vital maintenance of cellular energy balance. Previously published studies have demonstrated that autophagy is closely related to NAFLD occurrence and maternal obesity increases the susceptibility of offspring to non-alcoholic fatty liver disease, however, the underlying mechanism of this remains unclear. In the present study, NAFLD mouse models (offspring of an obese mother mouse via high-fat feeding) were generated, and the physiological indices of the liver were observed using total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein serum assay kits. The morphological changes of the liver were also observed via HE, Masson and oil red O staining. Reverse transcription-quantitative-PCR and western blotting were performed to detect changes of autophagy-related genes in liver or fibrosis marker proteins (α-smooth muscle actin or TGF-β). Changes in serum inflammatory cytokine IL-6 levels were determined via ELISA. The results of the present study demonstrated that the offspring of an obese mother were more likely to develop NALFD than the offspring of a chow-fed mother, due to their increased association with liver fibrosis. When feeding continued to 17 weeks, the worst cases of NAFLD were observed and the level of autophagy decreased significantly compared with the offspring of a normal weight mouse. In addition, after 17 weeks of feeding, compared with the offspring of a chow-fed mother, the offspring of an obese mouse mother had reduced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation levels and increased mammalian target of rapamycin (mTOR) phosphorylation levels. These results suggested that a reduced level of AMPK/mTOR mediated autophagy may be of vital importance for the increased susceptibility of offspring to NAFLD caused by maternal obesity. In conclusion, the current study provided a new direction for the treatment of NAFLD in offspring caused by maternal obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120514PMC
July 2021

Tracking petrogenic hydrocarbons in lakes of the Peace-Athabasca Delta in Alberta, Canada using petroleum biomarkers.

Environ Pollut 2021 Oct 3;286:117286. Epub 2021 May 3.

University of Ottawa, Ottawa, Ontario, Canada. Electronic address:

The Peace-Athabasca Delta (PAD) receives a mixture of hydrocarbons from biogenic, pyrogenic, and petrogenic processes. Source apportionment in the PAD has focussed on polycyclic aromatic compounds (PACs), which are ubiquitous in the environment and susceptible to weathering. In contrast, petroleum biomarkers of terpanes, hopanes, and steranes are degradation-resistant organic compounds found uniquely in petroleum products that can identify the input and origin of petrogenic hydrocarbons (PHCs). We provide an analysis of environmentally-relevant PHCs (including n-alkanes, PACs, and petroleum biomarkers) in surficial sediments of strategically selected lakes in the Athabasca and Peace deltas and adjacent boreal uplands. Alkanes were found to be predominately biogenic in all lakes. PAC sources were identified as wood combustion in the upland boreal lakes, a mixture of petrogenic and pyrogenic combustion in two closed-drainage lakes in the Peace Delta, and predominately petrogenic in two flood-prone Athabasca Delta lakes. Using multivariate analyses, raw Alberta oil sands were identified as a potential source of PHCs to the two flood-prone lakes in the Athabasca Delta. Biomarkers of terpanes and hopanes were identified in the Peace Delta and boreal uplands, likely from bitumen and transported atmospherically. These findings validate the use of petroleum biomarkers as tracers for bituminous sands in surficial lake sediments and their potential use in paleolimnological investigations at the PAD to improve understanding of relative roles of natural and industrial processes on far-field deposition of PHCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.117286DOI Listing
October 2021

Prenatal diagnosis of megaduodenum using ultrasound: a case report.

BMC Pregnancy Childbirth 2021 May 11;21(1):370. Epub 2021 May 11.

Department of Ultrasound, Shengjing Hospital of China Medical University, No.36 Sanhao St, Shenyang, 110004, Liaoning, China.

Background: Congenital megaduodenum is a rare disorder; however, its prenatal diagnosis has not been reported previously. We report the case of an abdominal cystic mass in a fetus that was later diagnosed as megaduodenum.

Case Presentation: An abdominal cystic mass was found during ultrasonography of a fetus at 11 weeks of gestation. The mass progressively enlarged with gestation. The amniotic fluid volume decreased and then returned to normal. During the last prenatal ultrasound examination, the mass was observed communicating with the stomach; therefore, duodenal dilation was suspected. Finally, the patient was diagnosed with megaduodenum caused by a developmental defect in the nerve plexus.

Conclusions: Congenital megaduodenum is a differential diagnosis of massive fetal abdominal cystic masses. Ultrasound examinations of such masses communicating with the stomach may help determine the diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-021-03843-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111774PMC
May 2021

Switching the secondary and natural activity of Nitrilase from Acidovorax facilis 72 W for the efficient production of 2-picolinamide.

Biotechnol Lett 2021 Aug 7;43(8):1617-1624. Epub 2021 May 7.

State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.

Objectives: Catalytic promiscuity, or the ability to catalyze a secondary reaction, provides new opportunities for industrial biocatalysis by expanding the range of biocatalytic reactions. Some nitrilases converting nitriles to amides, referred to as the secondary activity, show great potential for amides production. And our goal was exploiting the amide-forming potential of nitrilases.

Results: In this study, we characterized and altered the secondary activity of nitrilase from Acidovorax facilis 72 W (Nit72W) towards different substrates. We increased the secondary activity of Nit72W towards 2-cyanopyridine by 196-fold and created activity toward benzonitrile and p-nitrophenylacetonitrile by modifying the active pocket. Surprisingly, the best mutant, W188M, completely converted 250 mM 2-cyanopyridine to more than 98% 2-picolinamide in 12 h with a specific activity of 90 U/mg and showed potential for industrial applications.

Conclusions: Nit72W was modified to increase its secondary activity for the amides production, especially 2-picolinamide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10529-021-03137-7DOI Listing
August 2021

Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.

Aging Cell 2021 06 6;20(6):e13370. Epub 2021 May 6.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.

Research on ageing-associated genes is important for investigating ageing and anti-ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3-HDAC complex and inhibits its deacetylated activity, leads to hyper-acetylation of the histones at the promoters of mTOR-related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing-associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208792PMC
June 2021

Two VQ Proteins are Substrates of the OsMPKK6-OsMPK4 Cascade in Rice Defense Against Bacterial Blight.

Rice (N Y) 2021 Apr 28;14(1):39. Epub 2021 Apr 28.

National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan, 430070, China.

Background: The plant-specific valine-glutamine (VQ) protein family with the conserved motif FxxxVQxLTG reportedly functions with the mitogen-activated protein kinase (MAPK) in plant immunity. However, the roles of VQ proteins in MAPK-mediated resistance to disease in rice remain largely unknown.

Results: In this study, two rice VQ proteins OsVQ14 and OsVQ32 were newly identified to function as the signaling components of a MAPK cascade, OsMPKK6-OsMPK4, to regulate rice resistance to Xanthomonas oryzae pv. oryzae (Xoo). Both OsVQ14 and OsVQ32 positively regulated rice resistance to Xoo. In vitro and in vivo studies revealed that OsVQ14 and OsVQ32 physically interacted with and were phosphorylated by OsMPK4. OsMPK4 was highly phosphorylated in transgenic plants overexpressing OsMPKK6, which showed enhanced resistance to Xoo. Meanwhile, phosphorylated OsVQ14 and OsVQ32 were also markedly accumulated in OsMPKK6-overexpressing transgenic plants.

Conclusions: We discovered that OsVQ14 and OsVQ32 functioned as substrates of the OsMPKK6-OsMPK4 cascade to enhance rice resistance to Xoo, thereby defining a more complete signal transduction pathway for induced defenses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12284-021-00483-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081811PMC
April 2021

An entry to 2-(cyclobut-1-en-1-yl)-1-indoles through a cyclobutenylation/deprotection cascade.

Org Biomol Chem 2021 May;19(18):4048-4053

Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, W12 0BZ London, UK.

A transition-metal-free strategy for the synthesis of 2-(cyclobut-1-en-1-yl)-1H-indoles under mild conditions is described herein. A series of substituted 2-(cyclobut-1-en-1-yl)-1H-indoles are accessed by a one-pot cyclobutenylation/deprotection cascade from N-Boc protected indoles. Preliminary experimental and density functional theory calculations suggest that a Boc-group transfer is involved in the underlying mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ob00430aDOI Listing
May 2021

Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review).

Oncol Rep 2021 03 22;45(3):846-856. Epub 2021 Jan 22.

Department of Breast and Thyroid Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401147, P.R. China.

Breast cancer is one of the most common malignancies in women and is characterized by active immunogenicity. Immune cell infiltration plays an important role in the development of breast cancer. The degree of infiltration influences both the response to and effect of treatment. However, immune infiltration is a complex process. Differences in oxygen partial pressure, blood perfusion and nutrients in the tumor microenvironment (TME) suggest that infiltrating immune cells in different sites experience different microenvironments with corresponding changes in the metabolic mode, that is, immune cell metabolism is heterogenous in the TME. Furthermore, the present review found that lipid metabolism can support the immunosuppressive microenvironment in breast cancer based on a review of published literature. Research in this field is still ongoing; however, it is vital to understand the metabolic patterns and effects of different microenvironments for antitumor therapy. Therefore, this review discusses the metabolic responses of various immune cells to different microenvironments in breast cancer and provides potentially meaningful insights for tumor immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2021.7946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859921PMC
March 2021

Knockdown of PC4 increases chemosensitivity of Oxaliplatin in triple negative breast cancer by suppressing mTOR pathway.

Biochem Biophys Res Commun 2021 03 29;544:65-72. Epub 2021 Jan 29.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China. Electronic address:

As a multifunctional nuclear protein, the human positive cofactor 4 (PC4) is highly expressed in various tumors including breast cancer and has potential roles in cancer development and progression. However, the functional signatures and molecular mechanisms of PC4 in triple negative breast cancer (TNBC) progression and chemotherapeutic response are still unknown. In this study, we found that PC4 is significantly upregulated in TNBC cells compared with non-TNBC cells, implying its potential role in TNBC. Then, in vivo and in vitro studies revealed that knockdown of PC4 increased chemosensitivity of Oxaliplation (Oxa) in TNBC by suppressing mTOR pathway. Therefore, our findings demonstrated the signatures and molecular mechanisms of PC4 in TNBC chemotherapeutic response, and indicated that PC4 might be a promising therapeutic target for TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.01.029DOI Listing
March 2021

Near-infrared oxidative phosphorylation inhibitor integrates acute myeloid leukemia-targeted imaging and therapy.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Acute myeloid leukemia (AML) is a deadly hematological malignancy with frequent disease relapse. The biggest challenge for AML therapy is the lack of methods to target and kill the heterogeneous leukemia cells, which lead to disease relapse. Here, we describe a near-infrared (NIR) fluorescent dye, IR-26, which preferentially accumulates in the mitochondria of AML cells, depending on the hyperactive glycolysis of malignant cell, and simultaneously impairs oxidative phosphorylation (OXPHOS) to exert targeted therapeutic effects for AML cells. In particular, IR-26 also exhibits potential for real-time monitoring of AML cells with an in vivo flow cytometry (IVFC) system. Therefore, IR-26 represents a novel all-in-one agent for the integration of AML targeting, detection, and therapy, which may help to monitor disease progression and treatment responses, prevent unnecessary delays in administering upfront therapy, and improve therapeutic efficiency to the residual AML cells, which are responsible for disease relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abb6104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775779PMC
January 2021

FIGNL1 promotes non‑small cell lung cancer cell proliferation.

Int J Oncol 2021 01 1;58(1):83-99. Epub 2020 Dec 1.

Department of Respiration and Critical Care Medicine, Anhui Provincial Key Laboratory of Clinical Basic Research on Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer‑associated mortality worldwide. In the present study, a novel molecular therapeutic target for lung cancer was investigated. The protein expression level of fidgetin‑like 1 (FIGNL1) in human lung cancer tissues was determined and its potential functions in the H1299 and A549 lung cancer cell lines was subsequently studied. In addition, the protein expression level of FIGNL1 in 109 lung cancer samples and corresponding para‑cancerous tissues was investigated, using immunohistochemical staining. RNA interference and overexpression of FIGNL1 was used to determine the role of FIGNL1 in regulating cell proliferation, and cDNA microarray analysis was performed to identify the potential regulatory pathways. Lastly, the potential role of FIGNL1 in regulating tumorigenesis in lungs and also the proliferation of lung cancer cells was investigated. Firstly, lung cancer tissues were found to express higher protein levels of FIGNL1 and was significantly associated with decreased cell proliferation, migration and invasion abilities, and enhanced cell death. Overexpression of FIGNL1 significantly promoted cell proliferation, including decreased arrest at the G1 phase of the cell cycle and apoptosis, as well as increased ability for fission and migration. These in vitro findings were consistent with the results of the cell‑line derived xenografts in BALB/c nude mice, where tumor growth was decreased when injected with cells transfected with shFIGNL1. Collectively, these results provide suggest that FIGNL1 is involved in cell growth and tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2020.5154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721085PMC
January 2021
-->