Publications by authors named "Linlin Liu"

238 Publications

The LRXs-RALFs-FER module controls plant growth and salt stress responses by modulating multiple plant hormones.

Natl Sci Rev 2021 Jan 30;8(1):nwaa149. Epub 2020 Jun 30.

Shanghai Center for Plant Stress Biology and Center of Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

Salt stress is a major environmental factor limiting plant growth and productivity. We recently discovered an important new salt tolerance pathway, where the cell wall leucine-rich repeat extensins LRX3/4/5, the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23 and receptor-like kinase FERONIA (FER) function as a module to simultaneously regulate plant growth and salt stress tolerance. However, the intracellular signaling pathways that are regulated by the extracellular LRX3/4/5-RALF22/23-FER module to coordinate growth, cell wall integrity and salt stress responses are still unknown. Here, we report that the LRX3/4/5-RALF22/23-FER module negatively regulates the levels of jasmonic acid (JA), salicylic acid (SA) and abscisic acid (ABA). Blocking JA pathway rescues the dwarf phenotype of the and mutants, while disruption of ABA biosynthesis suppresses the salt-hypersensitivity of these mutants. Many salt stress-responsive genes display abnormal expression patterns in the and mutants, as well as in the wild type plants treated with epigallocatechin gallate (EGCG), an inhibitor of pectin methylesterases, suggesting cell wall integrity as a critical factor that determines the expression pattern of stress-responsive genes. Production of reactive oxygen species (ROS) is constitutively increased in the and mutants, and inhibition of ROS accumulation suppresses the salt-hypersensitivity of these mutants. Together, our work provides strong evidence that the LRX3/4/5-RALF22/23-FER module controls plant growth and salt stress responses by regulating hormonal homeostasis and ROS accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nsr/nwaa149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288382PMC
January 2021

An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity.

Cell Chem Biol 2021 Oct 19. Epub 2021 Oct 19.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

The global epidemic caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in the infection of over 200 million people. To extend the knowledge of interactions between SARS-CoV-2 and humans, we systematically investigate the interactome of 29 viral proteins in human cells by using an antibody-based TurboID assay. In total, 1,388 high-confidence human proximal proteins with biotinylated sites are identified. Notably, we find that SARS-CoV-2 manipulates the antiviral and immune responses. We validate that the membrane protein ITGB1 associates angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 entry. Moreover, we reveal that SARS-CoV-2 proteins inhibit activation of the interferon pathway through the mitochondrial protein mitochondrial antiviral-signaling protein (MAVS) and the methyltransferase SET domain containing 2, histone lysine methyltransferase (SETD2). We propose 111 potential drugs for the clinical treatment of coronavirus disease 2019 (COVID-19) and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labeling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral infection and developing drugs for COVID-19 treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chembiol.2021.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527578PMC
October 2021

and for distinguishing between viral and bacterial infections in children with febrile illness.

Pediatr Investig 2021 Sep 22;5(3):195-202. Epub 2021 Sep 22.

Key Laboratory of Major Diseases in Children Ministry of Education Research Unit of Critical Infection in Children Chinese Academy of Medical Sciences 2019RU016 Department of Infectious Diseases Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse.

Objective: This study aimed to develop a novel biomarker assay that integrates and measurements to assist in differentiating between bacterial and viral infections.

Methods: This prospective study recruited children with febrile illness from two hospitals between July 1, 2018, and June 30, 2019. A panel of three experienced pediatricians performed reference standard diagnoses of all patients (i.e., bacterial or viral infection) using available clinical and laboratory data, including a 28-day follow-up assessment. Assay operators were blinded to the reference standard diagnoses. The expression levels of and were determined by quantitative real-time polymerase chain reaction assessment.

Results: Of 133 potentially eligible patients with suspected bacterial or viral infection, 35 were excluded after the application of exclusion criteria. The resulting cohort included 98 patients: 59 with viral diagnoses and 39 with bacterial diagnoses. The areas under the curve (AUCs) of diagnoses using and were 0.694 [95% confidence interval (): 0.583-0.804] and 0.751 (95% : 0.651-0.851), respectively. The disease risk score (DRS) [log( expression) - log( expression)] signature achieved an improved area under the receiver operating characteristic curve (AUC, 0.825; 95% : 0.735-0.915), compared with the AUC generated from individual host RNA. A combination of the DRS and the C-reactive protein (CRP) level achieved an AUC of 0.896 (95% : 0.825-0.966). Optimal cutoffs for the DRS and CRP level were -3.18 and 19.80 mg/L, respectively.

Interpretation: The DRS was significantly more accurate than the CRP level in distinguishing between bacterial and viral infections; the combination of these two parameters exhibited greater sensitivity and specificity. This study provides information that could be useful for the clinical application of and in terms of distinguishing between viral and bacterial infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ped4.12295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458721PMC
September 2021

Photo-thermo catalytic selective oxidation of cyclohexane by In-situ prepared nonstoichiometric Molybdenum oxide and Silver-palladium alloy composite.

J Colloid Interface Sci 2021 Sep 17;607(Pt 2):954-966. Epub 2021 Sep 17.

School of Light Industry and Chemical Engineering, Guangzhou Key Laboratory of Clean Transportation Energy Chemistry, Guangdong University of Technology, Guangzhou 510006, China.

The highly selective oxidation of cyclohexane to cyclohexanone and cyclohexanol (KA oil) is one of the most challenging issues in the chemical industry. However, the difficulty in attaining high selectivity and high conversion rate in parallel for the existing catalysts limits its practical application. In this paper, a novel photo-thermo synergistic catalyst was reported for the aerobic oxidation of cyclohexane. The uniform blue MoO nanowires with small diameter stabilized by polyvinyl pyrrolidone (PVP) were synthesized by a hydrothermal method, and a series of MoO-AgPd composite materials of different proportions were prepared by an in-situ reduction process. The morphology, crystalline structure, surface chemical bonding, photoelectrochemical properties of MoO-AgPd composites are thoroughly characterized. The MoO-AgPd composites present significantly increased catalytic performance than MoO nanowires in the photo-thermo synergistic catalytic oxidation of cyclohexane under dry air. The high conversion rate of 11.3% with the KA oil selectivity of 99.0% was achieved by the MoO-AgPd composites under photo-thermo catalytic process at 120 ℃, which is 1.5 times of that by MoO nanowires. Under photo-thermo catalytic process, a high cyclohexane conversion rate similar to that of higher temperature thermal catalysis can be obtained at lower reaction temperature, and more cyclohexanol can be produced with a ketone to alcohol (K/A) ratio of 0.254. The significantly enhanced catalytic activity can be attributed to the effective charge transfer in the AgPd alloy nanoparticles, the optimized band gap structure, the suppressed charge recombination, and the promoted photo-thermo synergetic catalytic effect. This work provides a new reference scheme for the design and preparation of high-efficiency photo-thermo catalysts for the selective oxidation of cyclohexane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.09.058DOI Listing
September 2021

Hypermethylation of the and promoter regions in Chinese Han males with alcohol use disorder in Yunnan Province.

Am J Drug Alcohol Abuse 2021 Sep 28:1-10. Epub 2021 Sep 28.

School of Forensic Medicine, Kunming Medical University, Kunming, China.

Background: Alcohol use disorder (AUD) is one of the most serious public health problems worldwide. The and genes are important factors in the reward and alcohol metabolism pathways, and their DNA methylation patterns are closely related to AUD and are population-specific. Chinese Han people are the most populous ethnic group in the world, and this group experiences severe AUD. No epigenetic study on and has been performed in Chinese Han patients with AUD.

Objectives: To investigate whether methylation patterns of and are associated with susceptibility to AUD in Chinese Han males.

Methods: DNA methylation of the and promoters was studied in Chinese Han males with AUD in Yunnan Province (N = 50 controls, N = 90 individuals with AUD) using the bisulfite pyrosequencing method.

Results: In the AUD group, compared with the control group, OPRM1 was hypermethylated(p < .01) but there was no significant difference in the methylation level of ALDH2 (p > .05). 9 CpG sites of OPRM1 (p < .05) and 2 CpG sites of ALDH2 (p > .01) were hypermethylated. Smoking promoted AUD-mediated hypermethylation of , in which 3 CpG sites showed significant hypermethylation ( < .01). Age had no significant effect on the DNA methylation levels of these two genes.

Conclusions: Our study demonstrates that DNA hypermethylation of the and promoter regions is associated with an increased risk of AUD, which may help to explain the pathogenesis and progression of AUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00952990.2021.1973486DOI Listing
September 2021

Identification of Potential Prognostic Biomarker for Predicting Survival in Multiple Myeloma Using Bioinformatics Analysis and Experiments.

Front Genet 2021 10;12:722132. Epub 2021 Sep 10.

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Multiple myeloma (MM) is a malignant disease of plasma cells, which remains incurable because of its unclear mechanism and drug resistance. Herein, we aimed to explore new biomarkers and therapeutic targets in MM. After screening differentially expressed genes (DEGs) in GSE6477 and GSE13591 dataset, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs using DAVID online database. The results indicated that the downregulated DEGs were mainly enriched in the immune-associated biological process. The protein-protein interaction network was constructed by STRING database, on which we performed module analysis and identified key genes. Gene set enrichment analysis (GSEA) and Kaplan-Meier analysis showed that RRM2 could be a novel biomarker in MM diagnosis. We further confirmed that novel RRM2 inhibitor osalmid inhibited MM cell proliferation and triggered cell cycle S phase arrest. Targeting RRM2 was expected to develop new therapeutic strategies for malignant MM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.722132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461066PMC
September 2021

A 3,000-year-old, basal S. enterica lineage from Bronze Age Xinjiang suggests spread along the Proto-Silk Road.

PLoS Pathog 2021 Sep 21;17(9):e1009886. Epub 2021 Sep 21.

School of Life Sciences, Jilin University, Changchun, China.

Salmonella enterica (S. enterica) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S. enterica. We reconstructed S. enterica genomes from those individuals, which form a previously undetected phylogenetic branch basal to Paratyphi C, Typhisuis and Choleraesuis-the so-called Para C lineage. Based on pseudogene frequency, our analysis suggests that the ancient S. enterica strains were not host adapted. One genome, however, harbors the Salmonella pathogenicity island 7 (SPI-7), which is thought to be involved in (para)typhoid disease in humans. This offers first evidence that SPI-7 was acquired prior to the emergence of human-adapted Paratyphi C around 1,000 years ago. Altogether, our results show that Salmonella enterica infected humans in Eastern Eurasia at least 3,000 years ago, and provide the first ancient DNA evidence for the spread of a pathogen along the Proto-Silk Road.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486138PMC
September 2021

Forensic genetic polymorphisms of 16 X-STR loci in the Yunnan Miao population and their relationship to other Chinese groups.

Leg Med (Tokyo) 2021 Nov 27;53:101961. Epub 2021 Aug 27.

School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, People's Republic of China; Judicial Expertise Center of Kunming Medical University, Kunming, Yunnan Province, People's Republic of China. Electronic address:

Allele frequencies for 16 X-chromosomal STR (X-STR) loci were obtained from a sample set of 440 unrelated Yunnan Miao individuals in China. A total of 117 alleles were observed in this group, with allele frequencies ranging from 0.0016 to 0.7565. The most informative marker for the studied population was DXS10134, with a polymorphism information content (PIC) of 0.8499, and the least polymorphic locus was DXS6810 (PIC = 0.3071). The power of discrimination (PD) varied from 0.4046 (DXS6800) to 0.8642 (DXS10134) in males and from 0.6188 (DXS6800) to 0.9673 (DXS10134) in females. The combined PDM and PDF were 0.999999989975990 and 0.999999999999949, respectively. The combined MECD and MECT were 0.999983301904059 and 0.999999915883733, respectively. Furthermore, population genetic structure investigation between the Yunnan Miao and 20 other populations using principal component analysis (PCA), multidimensional scaling plot (MDS), and neighboring-joining (NJ) phylogenetic tree analyses illustrated significant genetic difference between the Yunnan Miao and the other populations. This study is the first to provide X chromosome genetic polymorphism data of the Miao population in Yunnan Province and can be used as a supplementary reference to enrich the national database.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.legalmed.2021.101961DOI Listing
November 2021

Trans-ethnic genome-wide association study of severe COVID-19.

Commun Biol 2021 08 31;4(1):1034. Epub 2021 Aug 31.

College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-02549-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408224PMC
August 2021

TGAN: A simple model update strategy for visual tracking via template-guidance attention network.

Neural Netw 2021 Aug 16;144:61-74. Epub 2021 Aug 16.

School of Computer Science and Technology, Harbin Institute of Technology, Shenzhen, 518055, China. Electronic address:

Visual attention has been widely used in various fields of visual tasks in recent years. Recently, visual trackers based on probabilistic discriminative model prediction (PrDiMP) and Siamese box adaptive network (SiamBAN) have attracted much attention due to their excellent performance and high efficiency. However, the target template of the model in both the PrDiMP and SiamBAN is not updated online, and feature vectors of the template image and the search image are independent of each other in the IoU-Net and Siamese frameworks. In this research, we proposed a template-guidance attention network in both the IoU-Net (denoted as TGAN-I) and Siamese (denoted as TGAN-S) frameworks for visual tracking. TGAN-I and TGAN-S can comprehensively utilize the feature information of the template image and search image, and provide an implicit way to update the template. By utilizing a simple template update strategy, the TGAN-I and TGAN-S trackers can be more robust under certain challenging conditions such as occlusion and deformation. Besides, we introduce a channel and spatial attention module in feature maps of the template image and search image for adaptive feature refinement. Deformable convolutional networks are further used to enhance the model generalization capability in various transformations aspect ratios and scales of tracking targets. To verify the effectiveness of the proposed method, we evaluate the TGAN-I and TGAN-S trackers on six benchmarks and achieve state-of-the-art results. In particular, the TGAN-I method outperforms the strong baseline, PrDiMP, by 0.323 → 0.355 and 0.471 → 0.501 of EAO score on VOT2019 and VOT2016, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neunet.2021.08.010DOI Listing
August 2021

Urinary phthalate metabolites mixture, serum cytokines and renal function in children: A panel study.

J Hazard Mater 2021 Aug 20;422:126963. Epub 2021 Aug 20.

Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Epidemiological evidence regarded the relations of phthalates with children's renal function and its underlying mechanism were largely unknown. We conducted a panel study using 287 paired urine-blood samples by repeated measurements of 103 children (4-13 years) across 3 seasons to explore effects of urinary phthalate metabolites on estimated glomerular filtration rate (eGFR) and the potential role of multiple cytokines. We found that mono-ethyl phthalate (MEP), monobutyl phthalate (MBP), mono-benzyl phthalate (MBzP) and mono-n-octyl phthalate (MOP) were significantly associated with eGFR reduction. Compared with the lowest quartile, MBP, MBzP and MEP in the third and fourth quartiles exhibited a graded decrease in eGFR. Meanwhile, weighted quantile sum regression analyses showed an inverse association of metabolites mixture with eGFR, to which MEP, MBzP, MOP were the major contributors. MEP also remained robust in multiple-phthalate model. Age and weight status might modify such relationships with significant interactions. Furthermore, eGFR related phthalate metabolites were associated with increased multiple cytokines, and CCL27, CXCL1 might be potential mediators between MEP and eGFR with mild mediated proportions. Accordingly, urinary phthalate metabolites were related to eGFR reduction in dose-response manner and multiple cytokines elevation, of which CCL27 and CXCL1 might partly mediate phthalate-associated decreased renal function among children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126963DOI Listing
August 2021

The Ameliorative Effects of Arctiin and Arctigenin on the Oxidative Injury of Lung Induced by Silica via TLR-4/NLRP3/TGF- Signaling Pathway.

Oxid Med Cell Longev 2021 17;2021:5598980. Epub 2021 Jul 17.

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

Silicosis remains one of the most serious diseases worldwide, with no effective drug for its treatment. Our research results have indicated that arctiin and arctigenin could increase the mitochondrial membrane potential, which in turn reduces the production of reactive oxygen species (ROS), blocks the polarization of macrophages, and inhibits the differentiation of myofibroblasts to reduce oxidative stress, inflammation, and fibrosis. Further, our study revealed that arctiin and arctigenin suppressed the activation of NLRP3 inflammasome through the TLR-4/Myd88/NF-B pathway and the silica-induced secretion of TNF-, IL-1, TGF-, and -SMA. Besides, the silica-induced increase in the levels of serum ceruloplasmin and HYP was also inhibited. Results of metabolomics indicated that arctiin and arctigenin could regulate the abnormal metabolic pathways associated with the development of silicosis, which involve pantothenate and CoA biosynthesis, cysteine and methionine metabolism, linoleic acid metabolism, and arginine and proline metabolism successively. Furthermore, the analysis of metabolomics, together with network topological analysis in different phases of silicosis, revealed that urine myristic acid, serum 4-hydroxyproline, and L-arginine could be regarded as diagnosis biomarkers in the early phase and formation of pulmonary fibrosis in the latter phases of silicosis. Arctiin and arctigenin could downregulate the increased levels of myristic acid in the early phase and serum 4-hydroxyproline in the latter phase of silicosis. Interestingly, the integration of TLR-4/NLRP3/TGF- signaling and metabolomics verified the importance of macrophage polarization in the silicosis fibrosis process. To the best of our knowledge, this is the first study reporting that arctiin and arctigenin both can ameliorate silicosis effectively, and the former is a little stronger than its aglycone arctigenin because of its high oral bioavailability, low toxicity, and multimolecular active metabolites as determined by AdmetSAR and molecular docking analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5598980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313330PMC
July 2021

Anti-F4/80 treatment attenuates Th2 cell responses: Implications for the role of lung interstitial macrophages in the asthmatic mice.

Int Immunopharmacol 2021 Oct 24;99:108009. Epub 2021 Jul 24.

Department of Respiratory & Critical Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. Electronic address:

Lung interstitial macrophages (IMs) can be polarized towards an alternative activation phenotype in ovalbumin (OVA)-induced asthmatic mice. However, the role of alternative activation of lung IMs in Th2 cell responses in the asthmatic murine is still unclear. Here, we leverage an anti-F4/80 treatment which has been shown to selectively deplete IMs in mice and investigate how this treatment modulates Th2 cell responses in lung and whether the modulation is dependent on lung IMs in murine models of asthma. We show that anti-F4/80 treatment alleviates Th2 cell responses in mice immunized and challenged with OVA or house dust mite (HDM). The anti-F4/80 treatment does not target lung alveolar macrophages (AMs) in OVA-induced asthmatic mice or impact the abundance of other immune cell types, including B cells, T cells, and NK cells in wild-type mice. However, this treatment does inhibit the expression of polarized markers of alternatively activated macrophages, including arginase-1, Ym-1, and Fizz-1 in the lung tissues from OVA-induced asthmatic mice. Furthermore, we find that the inhibitory effects of anti-F4/80 treatment on Th2 cell responses can be reversed upon adoptive transfer of lung IMs. Taken together, our data show that anti-F4/80 treatment attenuates Th2 cell responses, which is at least partially related to depletion of lung IMs in murine models of asthma. This suggests that targeted lung IMs may provide a potential therapeutic protocol for the treatment of asthmatics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.108009DOI Listing
October 2021

Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway.

Redox Biol 2021 10 13;46:102069. Epub 2021 Jul 13.

Center of Reproduction, Development & Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, China. Electronic address:

Ischemic stroke is one of the leading causes of death and disability among adults. Despite the economic burden of the disease, available treatment options are still very limited. With the exception of anti-thrombolytics and hypothermia, current therapies fail to reduce neuronal injury, neurological deficits and mortality rates, suggesting that the development of novel and more effective therapies against ischemic stroke is urgent. In the present study, we found that artemether, which has been used in the clinic as an anti-malarial drug, was able to improve the neurological deficits, attenuate the infarction volume and the brain water content in a middle cerebral artery occlusion (MCAO) animal model. Furthermore, artemether treatment significantly suppressed cell apoptosis, stimulated cell proliferation and promoted the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), P90 and cAMP responsive element-binding protein (CREB). Artemether protective effect was attenuated by PD98059, an ERK1/2 inhibitor, administration. Similarly, in oxygen-glucose deprivation/reperfusion (OGD/RP) cell models, artemether pre-treatment induced the suppression of the intracellular ROS, the down-regulation of LDH activity, the reduction of caspase 3 activity and of the apoptosis cell rate and reversed the decrease of mitochondrial membrane potential. As with MCAO animal model, artemether promoted the activation of Erk1/2-P90-CREB signaling pathway. This effect was blocked by the inhibition or knock-down of ERK1/2. The present study provides evidences of the neuroprotective effect of artemether unravelling its potential as a new therapeutic candidate for the prevention and treatment of stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2021.102069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327154PMC
October 2021

Discovery of Orally Bioavailable Ligand Efficient Quinazolindiones as Potent and Selective Tankyrases Inhibitors.

ACS Med Chem Lett 2021 Jun 13;12(6):1005-1010. Epub 2021 May 13.

Virtual PoC DPU, Alternative Discovery and Development, IVIVT, Platform Technologies and Sciences, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States.

We report herein the discovery of quinazolindiones as potent and selective tankyrase inhibitors. Elucidation of the structure-activity relationship of the lead compound led to truncated analogues that have good potency in cells, pharmacokinetic (PK) properties, and excellent selectivity. Compound exhibited excellent potencies in cells and proliferation studies, good selectivity, activities, and an excellent PK profile. Compound also inhibited H292 xenograft tumor growth in nude mice. The synthesis, biological, pharmacokinetic, efficacy studies, and safety profiles of compounds are presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsmedchemlett.1c00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201761PMC
June 2021

Oncostatin M Maintains Naïve Pluripotency of mESCs by Tetraploid Embryo Complementation (TEC) Assay.

Front Cell Dev Biol 2021 26;9:675411. Epub 2021 May 26.

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

It has been well established that leukemia inhibitory factor (LIF) is essential for maintaining naïve pluripotency of embryonic stem cells (ESCs). Oncostatin M (OSM) is a member of the IL-6 family of cytokines which share gp130 as a receptor subunit, and the OSM-gp130 complex can recruit either LIF receptor β or OSM receptor β. Here we show that OSM can completely replace LIF to maintain naïve pluripotency of ESCs. Mouse ESCs (mESCs) cultured in the presence of LIF or OSM not only express pluripotency genes at similar levels but also exhibit the same developmental pluripotency as evidenced by the generation of germline competent chimeras, supporting previous findings. Moreover, we demonstrate by tetraploid embryo complementation assay, the most stringent functional test of authentic pluripotency that mESCs cultured in OSM produce viable all-ESC pups. Furthermore, telomere length and telomerase activity, which are also crucial for unlimited self-renewal and genomic stability of mESCs, do not differ in mESCs cultured under OSM or LIF. The transcriptome of mESCs cultured in OSM overall is very similar to that of LIF, and OSM activates Stat3 signaling pathway, like LIF. Additionally, OSM upregulates pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and steroid and retinol metabolic pathways. Although the significance of these pathways remains to be determined, our data shows that OSM can maintain naïve pluripotent stem cells in the absence of LIF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.675411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189179PMC
May 2021

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection.

Cell Mol Immunol 2021 07 7;18(7):1832-1834. Epub 2021 Jun 7.

Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-021-00708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182358PMC
July 2021

Preoperative interventional artery embolization for the treatment of a giant malignant phyllodes tumor: A case report.

Mol Clin Oncol 2021 Jul 11;15(1):133. Epub 2021 May 11.

First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

Phyllodes tumors (PTs) are rare but complex fibroepithelial lesions of the breast. The present report describes an unusual case of a giant malignant PT with a rich blood supply treated with dominant blood supply internal thoracic artery interventional embolization before surgery. A 41-year-old woman without underlying systemic disease presented with a tumor >20 cm in diameter growing rapidly in the left breast. Radiological results indicated a giant circular tumor with a clear boundary occupying the whole breast, possible invasion of the major pectoralis muscle and several enlarged lymph nodes in the left axillary region. Computed tomography angiography showed a large mass with a rich and powerful blood vessel supply and preoperative interventional embolization was performed to block the internal thoracic artery. Three days after artery embolization, mastectomy and grade I axillary lymph node dissection were performed. The giant tumor measured 17x16x11 cm. The surgery successfully treated the pain and tumor necrosis and the patient received chemotherapy and local radiotherapy. No recurrence was found at the 14-month follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2021.2295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138852PMC
July 2021

Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101.

Theranostics 2021 3;11(12):5955-5969. Epub 2021 Apr 3.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8 T cells and tumor burden. Here, a novel concept of vascular disruption and normalization dependent on a polymeric vascular disrupting agent (VDA) poly (-glutamic acid)--methoxy poly (ethylene glycol)/combretastatin A4 (CA4-NPs) + a vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) inhibitor DC101 is applied to improve anti-PD-1 therapy, wherein CA4-NPs reduce tumor burden and DC101 simultaneously increases the number of intratumoral CD8 T cells, successfully regulating the abovementioned imbalance in an H22 tumor model. Blood vessel density, tumor cell proliferation, and necrosis were evaluated to reveal the effects on reducing tumor burden by CA4-NP treatment. Pericyte coverage of blood vessels, tumor blood vessel perfusion, tumor hypoxia, and intratumoral immune cells were examined to verify their role in vascular normalization and immune cell homing of DC101. Furthermore, the effects of CA4-NPs + DC101 on reducing tumor burden and increasing the number of immune cells were studied. Finally, tumor suppression, intratumoral CD8 T cell activation, and the synergistic effects of anti-PD-1 combined with CA4-NPs + DC101 were verified. The tumor inhibition rate of anti-PD-1 antibody combined with CA4-NPs + DC101 reached 86.4%, which was significantly higher than that of anti-PD-1 (16.8%) alone. Importantly, the Q value reflecting the synergy between CA4-NPs + DC101 and anti-PD-1 was 1.24, demonstrating a strong synergistic effect. Furthermore, CA4-NPs + DC101 improved anti-PD-1 therapy by increasing the number of intratumoral CD8 T cells (anti-PD-1, 0.31% vs triple drug combination, 1.18%). These results reveal a novel approach to enhance anti-PD-1 therapy with VDAs + VEGF/VEGFR2 inhibitors in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.58164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058708PMC
July 2021

The predictive value of serum procalcitonin for non-invasive positive pressure ventilation in the patients with acute exacerbation of chronic obstructive pulmonary disease.

Medicine (Baltimore) 2021 Apr;100(16):e25547

Department of Respiratory and Critical Care Medicine.

Abstract: This study aimed to estimate the value of serum procalcitonin (PCT) for non-invasive positive pressure ventilation (NIPPV) prediction in the patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).A total of 220 AECOPD patients were divided into NIPPV group (n = 121) and control group (routine treatment, n = 99) based on the routine standards and physicians' experience. Logistic regression analysis was performed to identify the independent factors for NIPPV treatment. Additionally, the predictive values of the factors were measured through receiver operation characteristic (ROC) curve.NIPPV group and control group showed significant differences in respiratory rate (RR), PaO2, PaCO2, pH, oxygenation index, erythrocyte sedimentation rate (ESR), neutrophil, CRP (C-reaction protein), and PCT (P < .05 for all). PCT, CRP, PaCO2, RR, and neutrophil were independently correlated with NIPPV treatment in AECOPD. ROC curve showed that PCT had superior predictive value, with AUC of 0.899, the sensitivity of 86%, and the specificity of 91.9%. The cut-off value of serum PCT for NIPPV prediction was 88.50 ng/l.AECOPD patients who require NIPPV treatment frequently have high levels of PCT, CRP, PaCO2, RR and neutrophil. Serum PCT may be employed as an indicator for NIPPV treatment in AECOPD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078461PMC
April 2021

Deficiency Leads to Premature Ovarian Failure.

Front Cell Dev Biol 2021 23;9:644135. Epub 2021 Mar 23.

Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, China.

Tet enzymes participate in DNA demethylation and play critical roles in stem cell pluripotency and differentiation. DNA methylation alters with age. We find that deficiency reduces fertility and leads to accelerated reproductive failure with age. Noticeably, -deficient mice at young age exhibit dramatically reduced follicle reserve and the follicle reserve further decreases with age, phenomenon consistent with premature ovarian failure (POF) syndrome. Consequently, deficient mice become infertile by reproductive middle age, while age matched wild-type mice still robustly reproduce. Moreover, by single cell transcriptome analysis of oocytes, deficiency elevates organelle fission, associated with defects in ubiquitination and declined autophagy, and also upregulates signaling pathways for Alzheimer's diseases, but down-regulates X-chromosome linked genes, such as , which is known to be implicated in POF. Additionally, is aberrantly upregulated and endogenous retroviruses also are altered in deficient oocytes. These molecular changes are consistent with oocyte senescence and follicle atresia and depletion found in premature ovarian failure or insufficiency. Our data suggest that enzyme plays roles in maintaining oocyte quality as well as oocyte number and follicle reserve and its deficiency can lead to POF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.644135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021788PMC
March 2021

Coexistence of Parallel and Rotary Stackings in the Lamellar Crystals of a Perylene Bisimide Dyad for Temperature-Sensitive Bicomponent Emission.

J Phys Chem Lett 2021 Apr 30;12(13):3373-3378. Epub 2021 Mar 30.

Institute of Polymer Optoelectronic Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, P. R. China.

Coexistence of rotationally π-π stacked columns and discrete slip-stacked dimers of perylene bisimide (PBI) chromophores is revealed by single crystal X-ray diffraction in the lamellar crystal of a head-to-tail linked PBI dyad. The rotary π-π stacked columnar moieties show H-type spectral character with relatively higher excitation energy, while the discrete slip-stacked π-π dimers have J-type spectral behavior with lower excitation energy. The lamellar crystals show relatively low photoluminescence efficiency of 12% at room temperature, while this dramatically increases to ∼90% at low temperature (80 K). Both of the rotary and slip-stacked moieties are emissive, and the nonradiative energy transfer processes between them are suppressed at low temperature, ensuring the highly efficient excimer-like long-lived fluorescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.1c00674DOI Listing
April 2021

Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients.

Sci Rep 2021 03 24;11(1):6811. Epub 2021 Mar 24.

NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85848-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990942PMC
March 2021

Publisher Correction: Effects of Thymoquinone on radiation enteritis in mice.

Sci Rep 2021 Mar 24;11(1):7151. Epub 2021 Mar 24.

Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin, 300192, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-83839-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990912PMC
March 2021

Relationship between HLA-DRB1 gene polymorphism and breast cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e25078

Department of Integrated TCM and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Background: Breast cancer is one of the common malignant tumors in women, which seriously affects women's physical and mental health and even life-threatening. The occurrence and development of breast cancer are closely related to genetic factors. Many studies have shown that human leukocyte antigen DRB1 is associated with the development of breast cancer, but lack evidence. This study aims to systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer.

Methods: The retrieval time of this study was from the establishment of the database to February 2021. The retrieval databases included CNKI, Wanfang, VIP and China Biomedical Database, PubMed, Embase, Web of Science, and the Cochrane Library. The retrieval objects were observational studies on the relationship between HLA-DRB1 gene polymorphism and breast cancer (including case--control studies, cross-sectional studies, and cohort studies). The language restrictions were English and Chinese. Two researchers independently extracted the data and assessed the quality of the included studies, and Stata 16.0 software was used for statistical analysis.

Results: This study will systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer based on existing studies.

Conclusion: This study will explore the early warning signal of breast cancer genetic susceptibility, and provide evidence-based medical evidence for clarifying the role of HLA-DRB1 gene polymorphism in breast cancer.

Osf Registration Number: DOI 10.17605/OSF.IO/847FQ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025078DOI Listing
March 2021

Ambient Ultraviolet B Signal Modulates Tea Flavor Characteristics via Shifting a Metabolic Flux in Flavonoid Biosynthesis.

J Agric Food Chem 2021 Mar 15;69(11):3401-3414. Epub 2021 Mar 15.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.

Tea leaves contain an extraordinarily high level of flavonoids that contribute to tea health benefits and flavor characteristics, but the regulatory mechanism of ambient ultraviolet B (UV-B) on tea flavonoid enrichment remains unclear. Here, we report that ambient UV-B modulates tea quality by inducing a metabolic flux in flavonoid biosynthesis. UV-B absence decreased bitter- and astringent-tasting flavonol glycosides (kaempferol-7--glucoside, myricetin-3--glucoside, and quercetin-7--glucoside) but increased non-galloylated catechins. Conversely, supplementary UV-B increased flavonols and decreased catechins in tea leaves. These responses were achieved via CsHY5, which mediates the UV-B-induced MYB12 activation and binds to the promoters of flavonoid biosynthetic genes (, , and ), leading to flavonoid changes. Transcriptomic data indicated that UV-B-induced tea flavonoid regulation is responsive to multiple biotic and abiotic environmental stresses. These findings improve our understanding of light-regulated tea astringency and bitterness underlying shading effects and seasonal light changes and provide novel insights into tea cultivation management and processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07009DOI Listing
March 2021

Pyrococcus furiosus Argonaute coupled with modified ligase chain reaction for detection of SARS-CoV-2 and HPV.

Talanta 2021 May 11;227:122154. Epub 2021 Feb 11.

State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China. Electronic address:

Infectious diseases caused by viruses such as SARS-CoV-2 and HPV have greatly endangered human health. The nucleic acid detection is essential for the early diagnosis of diseases. Here, we propose a method called PLCR (PfAgo coupled with modified Ligase Chain Reaction for nucleic acid detection) which utilizes PfAgo to only use DNA guides longer than 14-mer to specifically cleave DNA and LCR to precisely distinguish single-base mismatch. PLCR can detect DNA or RNA without PCR at attomolar sensitivities, distinguish single base mutation between the genome of wild type SARS-CoV-2 and its mutant spike D614G, effectively distinguish the novel coronavirus from other coronaviruses and finally achieve multiplexed detection in 70 min. Additionally, LCR products can be directly used as DNA guides without additional input guides to simplify primer design. With desirable sensitivity, specificity and simplicity, the method can be extended for detecting other pathogenic microorganisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2021.122154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875706PMC
May 2021

Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis.

Stem Cell Res Ther 2021 03 12;12(1):174. Epub 2021 Mar 12.

Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Taipa, Macau, SAR, China.

Background: Spinal cord injury (SCI) is a debilitating medical condition that can result in the irreversible loss of sensorimotor function. Current therapies fail to provide an effective recovery being crucial to develop more effective approaches. Mesenchymal stem cell (MSC) exosomes have been shown to be able to facilitate axonal growth and act as mediators to regulate neurogenesis and neuroprotection, holding great therapeutic potential in SCI conditions. This study aimed to assess the potential of human placental MSC (hpMSC)-derived exosomes on the functional recovery and reactivation of endogenous neurogenesis in an experimental animal model of SCI and to explore the possible mechanisms involved.

Methods: The hpMSC-derived exosomes were extracted and transplanted in an experimental animal model of SCI with complete transection of the thoracic segment. Functional recovery, the expression of neural stem/progenitor cell markers and the occurrence of neurogenesis, was assessed 60 days after the treatment. In vitro, neural stem cells (NSCs) were incubated with the isolated exosomes for 24 h, and the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinases (ERK), and cAMP response element binding (CREB) proteins were assessed by western blot.

Results: Exosomes were successfully isolated and purified from hpMSCs. Intravenous injections of these purified exosomes significantly improved the locomotor activity and bladder dysfunction of SCI animals. Further study of the exosomes' therapeutic action revealed that hpMSC-derived exosomes promoted the activation of proliferating endogenous neural stem/progenitor cells as denoted by the significant increase of spinal SOX2GFAP, PAX6Nestin, and SOX1KI67 cells. Moreover, animals treated with exosomes exhibited a significative higher neurogenesis, as indicated by the higher percentage of DCXMAP 2 neurons. In vitro, hpMSC-derived exosomes promoted the proliferation of NSCs and the increase of the phosphorylated levels of MEK, ERK, and CREB.

Conclusions: This study provides evidence that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-021-02248-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953814PMC
March 2021

Detection of SARS-CoV-2 by CRISPR/Cas12a-Enhanced Colorimetry.

ACS Sens 2021 03 8;6(3):1086-1093. Epub 2021 Mar 8.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

The outbreak of COVID-19 caused a worldwide public health crisis. Large-scale population screening is an effective means to control the spread of COVID-19. Reverse transcription-polymerase chain reaction (RT-qPCR) and serology assays are the most available techniques for SARS-CoV-2 detection; however, they suffer from either less sensitivity and accuracy or low instrument accessibility for screening. To balance the sensitivity, specificity, and test availability, here, we developed enhanced colorimetry, which is termed as a magnetic pull-down-assisted colorimetric method based on the CRISPR/Cas12a system (M-CDC), for SARS-CoV-2 detection. By this method, SARS-CoV-2 RNA from synthetic sequences and cultured viruses can be detected by the naked eye based on gold nanoparticle (AuNP) probes, with a detection limit of 50 RNA copies per reaction. With CRISPR/Cas12a-assisted detection, SARS-CoV-2 can be specifically distinguished from other closely related viruses. M-CDC was further used to analyze 41 clinical samples, whose performance was 95.12%, consistent with that of an approved Clinical RT-qPCR Diagnosis kit. The developed M-CDC method is not dependent on sophisticated instruments, which makes it potentially valuable to be applied for SARS-CoV-2 screening under poor conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.0c02365DOI Listing
March 2021

Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy.

Biomater Sci 2021 Apr 3;9(8):3019-3027. Epub 2021 Mar 3.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients receiving RT, the incidence rate remains less than 30%. One major limitation is the paucity of CD8 T cells within non-irradiated tumors. Here, cisplatin (CDDP) loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) are confirmed to increase CD8 T cells within non-irradiated tumors and boost the abscopal effect of RT plus anti-PD1, and more strongly than CDDP. Compared to RT and RT + CDDP, RT + CDDP-NPs induced greater immunogenic cell death (ICD) with enhanced proportion of Calreticulin Lewis lung cancer (LLC) cells (16.47%, 20.53% and 27.03%), along with which more CD8 T cells were infiltrated into CDDP-NP treated irradiated tumors in the unilateral LLC tumor model. In the bilateral LLC tumor model, RT + CDDP-NPs significantly induced more chemokine (C-X-C motif) ligand 10 (CXCL10) secretion (36.3, 44.19 and 56.37 pg mL), which corresponded to greater CD8 T cell infiltration in the non-irradiated tumors (0.19%, 0.20% and 0.72%). Finally, compared to RT + anti-PD1 and RT + anti-PD1 + CDDP, RT + anti-PD1 + CDDP-NPs significantly inhibited the growth of non-irradiated tumors more forcefully, as indicated by the respective tumor volumes of 1141, 1146 and 585 mm. This is the first study to show that CDDP-NPs can amplify RT-induced immune activation and break through the efficiency limitation of the RT plus anti-PD1 induced abscopal effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1bm00112dDOI Listing
April 2021
-->