Publications by authors named "Yang J"

60,475 Publications

Targeting Chaperone-Mediated Autophagy for Disease Therapy.

Curr Pharmacol Rep 2018 Jun 2;4(3):261-275. Epub 2018 May 2.

Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Purpose Of The Review: To reason that targeting chaperone-mediated autophagy (CMA) represents a promising approach for disease therapy, we will summarize advances in researches on the relationship between CMA and diseases and discuss relevant strategies for disease therapy by targeting the CMA process.

Recent Findings: CMA is a unique kind of selective autophagy in lysosomes. Under physiological conditions, CMA participates in the maintenance of cellular homeostasis by protein quality control, bioenergetics, and timely regulated specific substrate-associated cellular processes. Under pathological conditions, CMA interplays with various disease conditions. CMA makes adaptive machinery to address stress, while disease-associated proteins alter CMA which is involved in pathogeneses of diseases. As more proteins are identified as CMA substrates and regulators, dysregulation of CMA has been implicated in an increasing number of diseases, while rectifying CMA alteration may be a benefit for these diseases.

Summary: Alterations of CMA in diseases mainly including neurodegenerative diseases and many cancers raise the possibility of targeting CMA to recover cellular homeostasis as one potential strategy for therapy of relevant diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40495-018-0138-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445509PMC
June 2018

Inflammation is involved in response of gastric mucosal epithelial cells under simulated microgravity by integrated transcriptomic analysis.

Am J Transl Res 2021 15;13(8):9195-9207. Epub 2021 Aug 15.

Medical School of Chinese PLA Beijing 100853, China.

Astronauts suffer from inflammatory changes induced by microgravity during space flight. Microgravity can significantly affect the inflammatory response of various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and digestive system. The aim of this research was to identify the key genes and pathways of gastric mucosa affected by microgravity. Human gastric mucosal epithelial GES-1 cells were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The gene expression profiles of GES-1 cells were obtained using Illumina sequencing platform and differentially expressed genes were identified by DESeq2 software, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Subsequently, a protein-protein interaction (PPI) network was constructed. Compared with a normal gravity (NG) group, a total of 943 DEGs, including 192 downregulated genes and 751 upregulated genes, were identified. These DEGs were associated with findings that included response to interleukin-1, positive regulation of inflammatory response, and positive regulation of neuroinflammatory response. Furthermore, these DEGs were mainly enriched in herpes simplex virus 1 infection, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathway. Thus, 21 hub genes were identified from PPI network, including IL6, IL1B, ITGAM, CXCL8, ITGAX, CCL5, SERPINA1, APOE, CSF1R, VWF, GBP1, APOB, CYBB, HLA-DRB1, CD68, FGG, FGA, OASL, NOD2, OAS2 and FCGR2A. These findings suggested that simulated microgravity upregulated inflammation-related genes and pathways of GES-1 cells, which may play important roles in the response to microgravity and provide useful information for preventing mucosal damage in astronauts. In conclusion, this study revealed the key genes and pathways associated with simulated microgravity and indicated that simulated microgravity induced an inflammatory response in gastric mucosal epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430122PMC
August 2021

Overexpression of Nicotinamide N-methyltransferase mainly covers stroma of colorectal cancer and correlates with unfavorable survival by its product 1-MNA.

J Cancer 2021 26;12(20):6170-6181. Epub 2021 Aug 26.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, Zhejiang, People's Republic of China.

Accumulating evidence indicates that Nicotinamide N-methyltransferase (NNMT) is abnormally expressed in tumor tissues of several cancers including colorectal cancer (CRC) and associated with cancer progression. However, the distribution characteristics and the clinical value of each part of NNMT expression in CRC are still not fully understood. The purpose of this study is to determine the distribution of NNMT expression and its association with survival in CRC. By using the cancer genome atlas (TCGA) and clinical proteomic tumor analysis consortium (CPTAC), we firstly analyzed the difference of gene and protein levels of NNMT between CRC and normal colorectal tissue. Then, NNMT protein expressions were detected in 18 intraepithelial neoplastic samples and 177 CRC tumor samples through immunohistochemistry in our study cohort. Furthermore, the relationship between NNMT expression and clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) of CRC patients were analyzed by Pearson χ2 test and log-rank test, respectively, in public datasets and our study cohort. Lastly, the function of NNMT and its product 1-methyl-nicotinamide (1-MNA) on migration and invasion in colorectal cancer cells was analyzed by wound healing assay and transwell assay. We determined that higher NNMT expression in CRC tissues than normal tissues in both gene and protein level in TCGA and CPTAC datasets (all < 0.05). In addition, the strong relationships of NNMT expression with stromal cells were found in the TCGA cohort. Fortunately, our cohort could validate that the expression of NNMT in tumor stroma cell was significantly higher than that in tumor cell ( < 0.0001), and both of them were significantly higher than that in adjacent normal tissue (ANT) ( < 0.0001 and < 0.0001, respectively). Furthermore, the positive NNMT expression in tumor cell and stromal cell were associated with series of unfavorable clinical characteristics, including advanced TNM stage, lymph node metastasis, distant metastasis (all < 0.05). Also, higher NNMT was associated with unfavorable survival both in our study and public datasets, including TCGA and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE17538). Moreover, the functional experiments showed that stromal cells with high NNMT expression can secret 1-MAN to promote migration and invasion of CRC cells . In CRC, NNMT is overexpressed in tumor cells and stroma cells, and then mainly expressed in tumor stroma cells. Overexpression of NNMT in tumor cell and stroma cell both are associated with metastasis and unfavorable survival. Besides, stromal cells with high NNMT expression secrets 1-MAN to promote migration and invasion of CRC cells. Therefore, NNMT may be a potential prognostic indicator in CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.56419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425209PMC
August 2021

Involvement of bradykinin and bradykinin B1 receptor in patients with endometriosis.

Exp Ther Med 2021 Nov 1;22(5):1240. Epub 2021 Sep 1.

Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050091, P.R. China.

Endometriosis (EM), a benign aseptic inflammatory disease, is associated with the presence of endometrial foci. Pain, one of its typical symptoms, has been reported as a constant stressor, but the etiology and pathogenesis of EM-associated pain are unclear. In the present study, eutopic and ectopic endometrium samples from women with EM (n=50) and normal endometrium samples from control subjects (n=20) were collected. Serum levels of prostaglandin E (PGE), prostaglandin F2α (PGF2α) and bradykinin (BK) were measured using commercial ELISA kits. The expression of the BKB1 receptor (BKB1R) protein was evaluated by immunohistochemical staining and western blot assay. The mRNA expression of BKB1R was measured by reverse transcription-quantitative PCR. The results revealed that there was a substantial increase in the protein and mRNA expression of BKB1R, as well as the release of PGE, PGF2α and BK in the blood, in the EM group compared with that in the control group. Moreover, PGE, PGF2α and BK levels were significantly correlated with each other, as well as with the pain intensity of EM. The increased expression levels of BKB1R protein and mRNA were positively correlated with the pain degree of EM. Thus, these data indicated that BK and BKB1R were involved in the pathological onset of EM-associated pain and that they may play an important role in EM-related pain by inducing PGE and PGF2α. The data indicate a potential new therapeutic target for EM-related pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438668PMC
November 2021

GDF-15 Suppresses Atherosclerosis by Inhibiting oxLDL-Induced Lipid Accumulation and Inflammation in Macrophages.

Evid Based Complement Alternat Med 2021 7;2021:6497568. Epub 2021 Sep 7.

Department of Neurology, The First People's Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China.

The growth differentiation factor-15 (GDF-15) may be involved in atherosclerosis. However, the role of GDF-15 in atherosclerosis remains unclear. The main goal of this study was to verify the role and mechanism of GDF-15 in atherogenesis. We first compared the serum GDF-15 level between patients with coronary atherosclerosis and healthy people. And then one ApoE mouse model of atherosclerosis was used to explore the effects of GDF-15 on oxidized low-density lipoprotein (oxLDL) accumulation, atherosclerosis-related gene expression, and lipid accumulation-related protein expression in mouse macrophages. As a result, the level of serum GDF-15 in patients with coronary atherosclerosis was significantly higher than that in healthy people. In the mouse model, GDF-15 expression was elevated in the core of plaque, and it was secreted mainly by the macrophages. In addition, GDF-15 decreased oxLDL-induced lipid accumulation and inflammation activation in macrophages. GDF-15 decreased the mRNA expressions of CD36, LOX1, and TLR4 that are associated with lipoprotein accumulation in macrophages. Further study showed that GDF-15 might suppress oxLDL-induced lipoprotein accumulation via inhibiting CD36 and LOX1 and decrease inflammation in macrophages by inhibiting TLR4. Thus, GDF-15 may suppress atherosclerosis and plaque formation by inhibiting lipoprotein accumulation and inflammation activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6497568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443352PMC
September 2021

Genome-Wide Single Nucleotide Polymorphism Analysis Elucidates the Evolution of in Ulleung Island: The Genetic Consequences of Anagenetic Speciation.

Front Plant Sci 2021 2;12:706195. Epub 2021 Sep 2.

Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.

Of the two major speciation modes of endemic plants on oceanic islands, cladogenesis and anagenesis, the latter has been recently emphasized as an effective mechanism for increasing plant diversity in isolated, ecologically homogeneous insular settings. As the only flowering cherry occurring on Ulleung Island in the East Sea (concurrently known as Sea of Japan), Nakai has been presumed to be derived through anagenetic speciation on the island. Based on morphological similarities, Rehder distributed in adjacent continental areas and islands has been suggested as a purported continental progenitor. However, the overall genetic complexity and resultant non-monophyly of closely related flowering cherries have hindered the determination of their phylogenetic relationships as well as the establishment of concrete continental progenitors and insular derivative relationships. Based on extensive sampling of wild flowering cherries, including and from Ulleung Island and its adjacent areas, the current study revealed the origin and evolution of using multiple molecular markers. The results of phylogenetic reconstruction and population genetic structure analyses based on single nucleotide polymorphisms detected by multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq) and complementary cpDNA haplotypes provided evidence for (1) the monophyly of ; (2) clear genetic differentiation between (insular derivative) and (continental progenitor); (3) uncertain geographic origin of , but highly likely via single colonization from the source population of in the Korean Peninsula; (4) no significant reduction in genetic diversity in anagenetically derived insular species, i.e., , compared to its continental progenitor ; (5) no strong population genetic structuring or geographical patterns in the insular derivative species; and (6) MIG-seq method as an effective tool to elucidate the complex evolutionary history of plant groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.706195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445234PMC
September 2021

Corrigendum: Low-Dose Total Body Irradiation Can Enhance Systemic Immune Related Response Induced by Hypo-Fractionated Radiation.

Front Immunol 2021 3;12:745787. Epub 2021 Sep 3.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China.

[This corrects the article DOI: 10.3389/fimmu.2019.00317.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.745787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448506PMC
September 2021

Causal Effect of Visceral Adipose Tissue Accumulation on the Human Longevity: A Mendelian Randomization Study.

Front Endocrinol (Lausanne) 2021 1;12:722187. Epub 2021 Sep 1.

Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Objective: Observational studies have demonstrated a close relationship between obesity and longevity. The aim of this Mendelian randomization (MR) study is to investigate whether genetic determinants of visceral adipose tissue (VAT) accumulation are causally associated with longevity.

Methods: In this two-sample MR study, we used summary data of genetic determinants (single-nucleotide polymorphisms; p < 5 × 10) of VAT accumulation based on genome-wide association studies (GWASs). Longevity was defined as an age beyond the 90th or 99th survival percentile. The causal association of VAT accumulation with longevity was estimated with the inverse variance-weighted (IVW) method. Sensitivity analyses, including weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (PRESSO), were also employed to assess the stability of the IVW results.

Results: Our MR analysis used 221 genetic variants as instrumental variables to explore the causal association between VAT accumulation and longevity. In the standard IVW methods, VAT accumulation (per 1-kg increase) was found to be significantly associated with lower odds of surviving to the 90th (odds ratio [OR] = 0.69; 95% confidence interval [CI] 0.55 to 0.86, p = 8.32 × 10) and 99th (OR = 0.67; 95% CI 0.49 to 0.91, p = 0.011) percentile ages. These findings remained stable in sensitivity analysis.

Conclusion: This MR analysis identified a causal relationship between genetically determined VAT accumulation and longevity, suggesting that visceral adiposity may have a negative effect on longevity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.722187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440971PMC
September 2021

Rebleeding of Ruptured Intracranial Aneurysm After Admission: A Multidimensional Nomogram Model to Risk Assessment.

Front Aging Neurosci 2021 1;13:692615. Epub 2021 Sep 1.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Objective: Rebleeding is recognized as the main cause of mortality after intracranial aneurysm rupture. Though timely intervention can prevent poor prognosis, there is no agreement on the surgical priority and choosing medical treatment for a short period after rupture. The aim of this study was to investigate the risk factors related to the rebleeding after admission and establish predicting models for better clinical decision-making.

Methods: The patients with ruptured intracranial aneurysms (RIAs) between January 2018 and September 2020 were reviewed. All patients fell to the primary and the validation cohort by January 2020. The hemodynamic parameters were determined through the computational fluid dynamics simulation. Cox regression analysis was conducted to identify the risk factors of rebleeding. Based on the independent risk factors, nomogram models were built, and their predicting accuracy was assessed by using the area under the curves (AUCs).

Result: A total of 577 patients with RIAs were enrolled in this present study, 86 patients of them were identified as undergoing rebleeding after admission. Thirteen parameters were identified as significantly different between stable and rebleeding aneurysms in the primary cohort. Cox regression analysis demonstrated that six parameters, including hypertension [hazard ratio (HR), 2.54; = 0.044], bifurcation site (HR, 1.95; = 0.013), irregular shape (HR, 4.22; = 0.002), aspect ratio (HR, 12.91; < 0.001), normalized wall shear stress average (HR, 0.16; = 0.002), and oscillatory stress index (HR, 1.14; < 0.001) were independent risk factors related to the rebleeding after admission. Two nomograms were established, the nomogram including clinical, morphological, and hemodynamic features (CMH nomogram) had the highest predicting accuracy (AUC, 0.92), followed by the nomogram including clinical and morphological features (CM nomogram; AUC, 0.83), ELAPSS score (AUC, 0.61), and PHASES score (AUC, 0.54). The calibration curve for the probability of rebleeding showed good agreement between prediction by nomograms and actual observation. In the validation cohort, the discrimination of the CMH nomogram was superior to the other models (AUC, 0.93 vs. 0.86, 0.71 and 0.48).

Conclusion: We presented two nomogram models, named CMH nomogram and CM nomogram, which could assist in identifying the RIAs with high risk of rebleeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.692615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440913PMC
September 2021

Visual naked-eye detection of SARS-CoV-2 RNA based on covalent organic framework capsules.

Chem Eng J 2022 Feb 11;429:132332. Epub 2021 Sep 11.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, PR China.

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cej.2021.132332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433056PMC
February 2022

Multicenter study evaluating novel multi-specimen pooling assay for the detection of SARS-CoV-2: High sensitivity and high throughput testing.

J Microbiol Immunol Infect 2021 Sep 2. Epub 2021 Sep 2.

Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address:

Background/purpose: Mass screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to prevent the spread of coronavirus disease 2019 (COVID-19). Pooling samples can increase the number of tests processed. LabTurbo AIO 48 is an automated platform that allows ribonucleic acid extraction and sample analysis on the same instrument. We created a novel pooling assay on this platform for SARS-CoV-2 detection and demonstrated that the pooling strategy increases testing capacity without affecting accuracy and sensitivity.

Methods: Comparative limit of detection (LoD) assessment was performed on the LabTurbo AIO 48 platform and the current standard detection system based on real-time reverse transcription polymerase chain reaction (rRT-PCR) using 55 clinically positive samples. An additional 330 primary clinical samples were assessed.

Results: Six samples pooled into one reaction tube were detected in approximately 2.5 h using the World Health Organization rRT-PCR protocol. LabTurbo AIO 48 also demonstrated a higher throughput than our reference rRT-PCR assay, with an LoD of 1000 copies/mL. The overall percentage agreement between the methods for the 330 samples was 100%.

Conclusion: We created a novel multi-specimen pooling assay using LabTurbo AIO 48 for the robust detection of SARS-CoV-2, allowing high-throughput results; this assay will aid in better control and prevention of COVID-19. The diagnostic assay was cost-effective and time-efficient; thus, the pooling strategy is a practical and effective method for diagnosing large quantities of specimens without compromising precision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmii.2021.08.003DOI Listing
September 2021

Estimation of the relative contributions of forest areal expansion and growth to China's forest stand biomass carbon sequestration from 1977 to 2018.

J Environ Manage 2021 Sep 16;300:113757. Epub 2021 Sep 16.

State Key Laboratory of Resources and Environment Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Spatial Sciences Institute, University of Southern California, Los Angeles, CA, 90089, USA.

As a prominent part of global and regional terrestrial carbon (C) pools, increases in forest biomass C sinks can be attributed to either forest areal expansion (FAE) or increased biomass C density (IBCD). Accurate estimates of the relative contributions of FAE and IBCD to forest C sequestration can improve our understanding of forest C cycling processes and will help to formulate rational afforestation policies to cope with global warming. In this study, the Continuous Biomass Expansion Factor (CBEF) model and Forest Identity concept were used to map the spatiotemporal variation of the relative contribution of FAE and IBCD to the C sequestration of forest (natural and planted forests) in China and seven regions during the past 40 years. Our results suggest that: (1) total forest biomass C density and stocks of forest increased from 35.41 Mg C ha and 4128.50 Tg C to 43.95 Mg C ha and 7906.23 Tg C in China from 1977 to 2018, respectively; (2) for all forests, the IBCD has been a smaller contributor to C sinks than FAE in China from 1977 to 2018 (33.27 vs. 66.73%); (3) the contribution of FAE to C sinks is greater than that of IBCD in planted forests (63.99 vs. 36.01%), while in natural forests, IBCD has a larger contribution than FAE (57.82 vs. 42.18%) from 1977 to 2018 and the relative contribution of FAE has exceeded IBCD in the last decade; and (4) these patterns varied at the regional level such that the relative contribution of FAE increased for planted forests in most regions but for natural forests, IBCD gradually reached saturation and C stocks declined in northern regions in the last decade. The results from this study suggest that total biomass C sinks will keep increasing because of the increased forest area contributed by afforestation and the relatively young trees in planted forests. This study facilitates a more comprehensive assessment of forest C budgets and improves our understanding of ecological mechanisms of forest biomass carbon stock and dynamics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2021.113757DOI Listing
September 2021

Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor-Naive Advanced ALK-Positive Non-Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial.

J Thorac Oncol 2021 Aug 30. Epub 2021 Aug 30.

Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, England, United Kingdom SW3 6JJ.

Introduction: In the phase 3 ALTA-1L study of brigatinib in anaplastic lymphoma kinase (ALK) inhibitor-naive advanced ALK+ NSCLC, brigatinib demonstrated superior progression-free survival (PFS) versus crizotinib in 2 planned interim analyses. We report final efficacy, safety, and exploratory results.

Methods: Patients were randomized to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. Primary endpoint was blinded independent review committee (BIRC)-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy.

Results: 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up: 40.4 months), 3-year PFS by BIRC was 43% (brigatinib) versus 19% (crizotinib; median, 24.0 vs 11.1 months; HR: 0.48; 95% CI: 0.35-0.66). Median overall survival (OS) was not reached in either group (HR: 0.81; 95% CI: 0.53-1.22). Post hoc analyses suggested an OS benefit for brigatinib in patients with baseline brain metastases (HR: 0.43; 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib demonstrated efficacy superior to crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed.

Conclusions: At ALTA-1L final analysis, with longer follow-up brigatinib continued to demonstrate superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2021.07.035DOI Listing
August 2021

Cu and Zn exert a greater influence on antibiotic resistance and its transfer than doxycycline in agricultural soils.

J Hazard Mater 2021 Aug 26;423(Pt B):127042. Epub 2021 Aug 26.

Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China. Electronic address:

Livestock manure is a main source of heavy metals, antibiotics and antibiotic resistance genes (ARGs) in agricultural soils. The co-existence of heavy metals and ARGs needs to be systematically studied, since manure application is greatly encouraged. In this study, we examined soils for alterations in antibiotic resistance where doxycycline, Cu, and Zn were added equivalent to those found in typical pig manure applications. The results indicated that high levels of Cu inhibited soil respiration and urease for the first 10 days. Metagenomic analysis demonstrated that Cu and Zn additions caused profound alterations in bacterial community, metal resistance genes (MRGs) and mobile genetic elements. Among the differential ARGs, efflux pump genes took a significantly high ratio compared with control for the first 5 days, emphasizing their important roles in the profile of antibiotic resistance. Moreover, the number of differential MRGs was < 30 for doxycycline treatment, but 66-87 for Cu and Zn treatments. The number of differential integrative and conjugative elements was 3 for doxycycline treatment, and 6-13 for Cu and Zn treatments. Overall, high Cu and Zn levels caused a greater influence than did doxycycline on bacterial communities and transfer of antibiotic resistance in soil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.127042DOI Listing
August 2021

Platelet-rich plasma attenuates interleukin-1β-induced apoptosis and inflammation in chondrocytes through targeting hypoxia-inducible factor-2α.

Tissue Cell 2021 Sep 8;73:101646. Epub 2021 Sep 8.

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, 95 Yong an Road, Xicheng District, Beijing, 100050, China. Electronic address:

Osteoarthritis (OA) is a prevailing chronic disease in Orthopedics that characterized with severely damaged cartilage and subchondral bone, thus leading to profound disorders of synovial joints. Platelet-rich plasma (PRP) has been applied as a popular non-operative treatment option for promoting musculoskeletal healing. Our previous work demonstrated that PRP protected chondrocytes from interleukin-1β (IL-1β)-induced apoptosis in vitro. However, the underlying mechanism behind the treatment remains unclear. The current study aimed to unveil the molecular signaling underlying its protective role in chondrocytes. Rat chondrocytes were isolated from newborn Sprague Dawley rats and treated with 5 ng/mL IL-1β for 24 h. The expression of hypoxia-inducible factor 2α (HIF-2α) was determined in both mRNA and protein levels. Next, loss- and gain-of-function assays for HIF-2α were performed using small-interfering RNA (siRNA) specific for HIF-2α and adenovirus-mediated HIF-2α overexpression, respectively. In addition, cell apoptosis markers, matrix metalloproteinase (MMP)-1, 3, -9 and -13, and extracellular matrix-related genes were evaluated. Our results demonstrated that IL-1β induced distinct inflammation in chondrocytes. In addition, HIF-2α upregulated in the IL-1β-treated chondrocytes compared to the untreated cells. Interestingly, 10% PRP protected chondrocytes against IL-1β-induced apoptosis and matrix degradation, and meanwhile suppressed the HIF-2α activation. Furthermore, HIF-2α siRNA and HIF-2α overexpression experiments indicated that PRP induced chondroprotection through targeting HIF-2α. Taken together, our findings indicated that PRP attenuates IL-1β-induced chondrocyte apoptosis and inflammation at least partially through inhibiting HIF-2α.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tice.2021.101646DOI Listing
September 2021

5-Aminolaevulinic acid photodynamic therapy suppresses lipid secretion of primary sebocytes through AMPK/SREBP-1 pathway.

Photodiagnosis Photodyn Ther 2021 Sep 15:102537. Epub 2021 Sep 15.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Shanghai 200443. Electronic address:

Background: Acne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, its specific treatment mechanism remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT induced lipid secretion inhibition in acne vulgaris.

Methods: Primary human sebocytes and sebaceous gland of golden hamster were treated with/without ALA-PDT. Cell viability was evaluated by Live/Dead Cell assay. Fluorescence microscope was used to observe lipids secretion in sebocytes after Nile red staining. The expression of SREBP-1 after ALA-PDT was evaluated by qRT-PCR. Regulation of ALA-PDT on AMPK/SREBP-1 was evaluated by western blot.

Results: The results showed that ALA-PDT suppressed lipid secretion of primary human sebocytes. In addition, ALA-PDT could inhibit the expression of SREBP-1 in vitro. We also found that ALA-PDT activated AMPK pathway, down-regulating the expression of SREBP-1 in sebocytes after ALA-PDT.

Conclusions: These findings elucidate that ALA-PDT suppresses lipid secretion through AMPK/SREBP-1 pathway in treatment of acne vulgaris.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2021.102537DOI Listing
September 2021

Interplay of Tumor Microenvironment Factors and Cancer Stem Cell Enrichment in Pancreatic Ductal Adenocarcinoma.

Gastroenterology 2021 Sep 15. Epub 2021 Sep 15.

Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.09.024DOI Listing
September 2021

Exploring the human cerebral cortex using confocal microscopy.

Prog Biophys Mol Biol 2021 Sep 15. Epub 2021 Sep 15.

European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, FI, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, FI, Italy; National Institute of Optics (INO), National Research Council (CNR), Italy.

Cover-all mapping of the distribution of neurons in the human brain would have a significant impact on the deep understanding of brain function. Therefore, complete knowledge of the structural organization of different human brain regions at the cellular level would allow understanding their role in the functions of specific neural networks. Recent advances in tissue clearing techniques have allowed important advances towards this goal. These methods use specific chemicals capable of dissolving lipids, making the tissue completely transparent by homogenizing the refractive index. However, labeling and clearing human brain samples is still challenging. Here, we present an approach to perform the cellular mapping of the human cerebral cortex coupling immunostaining with SWITCH/TDE clearing and confocal microscopy. A specific evaluation of the contributions of the autofluorescence signals generated from the tissue fixation is provided as well as an assessment of lipofuscin pigments interference. Our evaluation demonstrates the possibility of obtaining an efficient clearing and labeling process of parts of adult human brain slices, making it an excellent method for morphological classification and antibody validation of neuronal and non-neuronal markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbiomolbio.2021.09.001DOI Listing
September 2021

Cellular heterogeneity and immune microenvironment revealed by single-cell transcriptome in venous malformation and cavernous venous malformation.

J Mol Cell Cardiol 2021 Sep 15. Epub 2021 Sep 15.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. Electronic address:

Venous malformation (VM) and cavernous venous malformation (CVM) are two types of vascular malformations. Even if the two diseases are similar in appearance and imaging, the distinct cellular components and signaling pathways between them might help distinguish the two from a molecular perspective. Here, we performed single-cell profiling of 35,245 cells from two VM samples and three CVM samples, with a focus on endothelial cells (ECs), smooth muscle cells (SMCs) and immune microenvironment (IME). Clustering analysis based on differential gene expression unveiled 11 specific cell types, and determined CVM had more SMCs. Re-clustering of ECs and SMCs indicated CVM was dominated by arterial components, while VM is dominated by venous components. Gene set variation analysis suggested the activation of inflammation-related pathways in VM ECs, and upregulation of myogenesis pathway in CVM SMCs. In IME analysis, immune cells were identified to accounted for nearly 30% of the total cell number, including macrophages, monocytes, NK cells, T cells and B cells. Notably, more macrophages and monocytes were discovered in VM, indicating innate immune responses might be more closely related to VM pathogenesis. In addition, angiogenesis pathway was highlighted among the significant pathways of macrophages & monocytes between CVM and VM. In VM, VEGFA was highly expressed in macrophages & monocytes, while its receptors were all abundantly present in ECs. The close interaction of VEGFA on macrophages with its receptors on ECs was also predicted by CellPhoneDB analysis. Our results document cellular composition, significant pathways, and critical IME in CVM and VM development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yjmcc.2021.09.004DOI Listing
September 2021

pH-Sensitive Molecular-Switch-Containing Polymer Nanoparticle for Breast Cancer Therapy with Ferritinophagy-Cascade Ferroptosis and Tumor Immune Activation.

Adv Healthc Mater 2021 Sep 17:e2100683. Epub 2021 Sep 17.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Ferritin internalized into tumor cells is degraded and releases iron ions via ferritinophagy. Iron ions participate in Fenton reaction to produce reactive oxygen species for lipid peroxidation and ferroptosis. Inhibition of indoleamine-2,3-dioxygenase (IDO) decreases tryptophan elimination to induce T cells activation for tumor immunosuppression relief. The active tumor targeting nanoparticles containing ferritin and a pH-sensitive molecular-switch ([email protected]) are developed to utilize ferritinophagy-cascade ferroptosis and tumor immunity activation for cancer therapy. [email protected] disintegrates in acidic cytoplasm and releases sorafenib (SRF) and IDO inhibitor (NLG919). SRF upregulates nuclear receptor coactivator 4 (NCOA4) to induce ferritin and endogenous iron pool degradation by ferritinophagy, then obtained iron ions participate in the Fenton reaction to produce lipid peroxide (LPO). Meanwhile, SRF blocks glutathione synthesis to downregulate glutathione peroxidase 4 (GPX4) which can scavenge LPO as a different pathway from ferritinophagy to promote ferroptosis in tumor cells. NLG919 inhibits IDO to reduce tryptophan metabolism, so immunity in tumors is aroused to anti-tumor. In vitro and in vivo experiments prove [email protected] inhibits tumor cell growth and metastasis, indicating the potential of [email protected] for breast cancer therapy based on the combination of ferritinophagy-cascade ferroptosis and tumor immunity activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202100683DOI Listing
September 2021

Plasmon-Enhanced, Self-Traced Nanomotors on the Surface of Silicon.

Angew Chem Int Ed Engl 2021 Sep 18. Epub 2021 Sep 18.

The Chinese University of Hong Kong, Department of Physics, Room G9, Science Center North Block, 852, Shatin, HONG KONG.

Light-driven nanomotors have attracted much attention due to their potential applications. The movement of conventional nanomotors typically occurs in the solution phase, which limits their application fields. Utilizing visible light to drive nanomotors at the solid-liquid interface represents a grand challenge due to the large friction force between the nanomotor and the solid surface. Based on the attractive plasmon resonance of Au nanocrystals, for the first time, plasmon-enhanced Au nanocrystal-based nanomotors moving at the silicon-aqueous solution interface have been developed. Such nanomotors move with a clear trace engraved on the Si surface, representing an excellent and exceptional self-traced nanomotor system. In addition, the nanomotor trace on the Si surface also provides a unique and promising approach to the fabrication of nanoscale Si patterns, which is central to many applications, including microelectronics, sensing, information storage, and optoelectronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202108487DOI Listing
September 2021

16S ribosomal assay for early diagnosis of gonococcal meningitis with negative CSF culture: A case report.

J Infect Chemother 2021 Sep 14. Epub 2021 Sep 14.

Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, China. Electronic address:

Gonococcal meningitis is an exceedingly rare infectious disease, and if not diagnosed and treated in time, it can be severe. We present a case of gonococcal meningitis occurring in a 31-year old healthy woman. She was admitted with fever and persistent headache without urogenital symptoms. Blood cultures were positive and identified as N.gonorrhoeae, but CSF and cervical secretions cultures were both negative. Further testing confirmed the presence of N.gonorrhoeae by 16S ribosomal gene amplification and sequencing in all samples. These results suggest that the case may be a disseminated infection caused by untreated gonorrhea. Our case also shows that nucleic acid detection plays an important role in the rapid and precise diagnosis of gonococcal meningitis and in finding the origin of the pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiac.2021.09.004DOI Listing
September 2021

Delayed coronary artery occlusion after transcatheter aortic valve replacement and chimney stenting: a case report.

BMC Cardiovasc Disord 2021 Sep 17;21(1):451. Epub 2021 Sep 17.

Fifth School of Clinical Medicine, Peking University, Beijing, People's Republic of China.

Background: Delayed coronary artery occlusion (CAO) is a rare but fatal complication after transcatheter aortic valve replacement, chimney stenting is the standard technique for established CAO or impending CAO.

Case Presentation: We describe a female patient who developed non-ST elevation myocardial infarction after receiving transcatheter aortic valve replacement and chimney stenting 4 months prior. An angiogram revealed delayed coronary artery occlusion with a deformed stent, which was never reported. This patient was subsequently treated with a new chimney stent.

Conclusions: For self-expanding valves, the coronary ostium is protected by chimney stenting, delayed coronary artery occlusion can occur and cause catastrophic complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-02249-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447508PMC
September 2021

Genetic characterization of Carbapenem-Resistant Escherichia coli from China, 2015-2017.

BMC Microbiol 2021 Sep 17;21(1):248. Epub 2021 Sep 17.

Laboratory Medicine Department, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.

Background: The molecular characteristics of carbapenem-resistant Escherichia coli (CREco) remain unclear.

Methods: We conducted a multi-center bacterial resistance monitoring project from 2015 to 2017.The minimum inhibitory concentrations ofCREco were determined bybroth microdilution method. The genome sequencing of CREcoisolates was performed, and single-nucleotide polymorphism (SNP) was analyzed.

Results: A total of 144CREcoisolatescollected from 10 cities in China were involved in this study. ST167 (n = 43) is the most popular type, followed by ST410(n = 14), ST131(n = 9). There were 102 (70.83%) CREco isolates that produced various NDMs, including NDM-1 (n = 16), NDM-4(n = 1), NDM-5(n = 79), NDM-6(n = 2) and NDM-9(n = 4). In addition, 15 isolates produced KPC-2, three isolates wereIMP-4 positive, and three isolates produced OXA-48. Genetic relatedness and phylogenetic analysis showed that isolates with the same ST had a high degree of homology. Some STs (including ST167, ST410, ST131, ST46, ST405 and ST617) exhibited a trend of outbreak.

Conclusions: The majority of CREco belonged to ST167, followed by ST410 and ST131, and most of them carried various NDM-coding genes. The spread of high-risk clones of CREco has occurred in different regions of China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02307-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449468PMC
September 2021

Difference in temporal and spatial distribution pattern of cyanobacteria between the sediment and water column in Lake Chaohu.

Environ Pollut 2021 Sep 11;291:118163. Epub 2021 Sep 11.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China. Electronic address:

The evaluation about the relative distribution of cyanobacterial biomass between the sediment and water column would be indispensable to understand if benthic cyanobacteria are important to cyanobacterial biomass in the water column. A separation method for the rapid quantification of benthic cyanobacteria in Lake Chaohu was developed by density-gradient centrifugation. A 2 full factorial design and response surface methodology was employed to optimize the extraction protocol. Under the optimal operating parameters including 29% Percoll solution, 30 min centrifugation time, 7200 r/min centrifugation speed, and a 1:10 ratio between the volume of sediment and Percoll solution, the recovery rate of cyanobacteria in sediment was 96.73%. Temporal and spatial variations in cyanobacterial biomass in water and sediment were investigated monthly throughout a whole year. In general, cyanobacterial biomass per square centimeter in the water column showed high spatial-temporal changes, tending to increase in February and reaching a peak in April at some sites due to the growth of Dolichospermum. The second peak arrived in July and September and was caused by the rapid growth of Microcystis. Concurrently, cyanobacteria biomass per unit area in sediment showed a clear temporal change pattern, increasing from October and reaching a peak level in February at all the sampling sites. The average ratio of cyanobacterial biomass in water to that in sediment was lowest in January at 1.48 and increased to the highest level in July at 318.61. Although Microcystis and Dolichospermum were dominant species in the water column, only Microcystis was observed in the Percoll solution extraction from sediment. Microscopic observation revealed that a very small fraction of Microcystis cells could survive in sediment, and most of the cells decomposed when the water temperature increased after June. Therefore, the contribution of the recruitment of cyanobacteria could be negligible in Lake Chaohu.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.118163DOI Listing
September 2021

Defect engineering in polymeric carbon nitride photocatalyst: Synthesis, properties and characterizations.

Adv Colloid Interface Sci 2021 Sep 9;296:102523. Epub 2021 Sep 9.

Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

Polymer carbon nitride (CN) has unique structure and electronic properties, making it attractive in photocatalysis fields. However, the photocatalytic efficiency of the pristine CN photocatalyst is still unsatisfactory. In this regard, the introduction of vacancy defects can effectively tune photoelectric properties of CN photocatalyst through tailoring the electronic structure and bandgap engineering. In this review, the effect of vacancy defects on CN is reviewed from the aspects of light absorption, charge separation and surface photoreactivity of CN. Meanwhile, the current progress in the design of vacancy defects with the classified carbon vacancies (CVs), nitrogen vacancies (NVs), amino and cyano groups on CN to boost the photocatalytic performance is summarized. Furthermore, various characterization methods have been summarized and highlighted, including microscopic characterization (SEM, TEM, AFM, HAADF-STEM), spectroscopic characterization (XRD, FTIR, XAFS, XANES, EPR, PAS, XPS, raman spectroscopy, solid-state NMR spectroscopy), elemental analysis, and computational characterization. Finally, the future opportunities and challenges of CN photocatalysts designed with vacancies and defects are proposed to highlight the development direction of this research field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cis.2021.102523DOI Listing
September 2021

Discovery of novel 2-phenylamino-4-prolylpyrimidine derivatives as TRK/ALK dual inhibitors with promising antitumor effects.

Bioorg Med Chem 2021 Sep 8;47:116396. Epub 2021 Sep 8.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

In order to explore novel TRK and ALK dual inhibitors, a series of 2-phenylamino-4-prolylpyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxicity and enzymatic activities. Delightfully, most compounds were detected moderated to excellent activities in cellular assay. Among them, compound 21 exhibited encouraging cytotoxicity on KM12, H2228 and KARPAS299 cells with IC values of 0.86, 0.141 and 0.072 μM. Meanwhile, the performances of 21 in the enzymatic assays were in good accordance with anti-proliferative activity with IC values of 2.2, 9.3 and 38 nM towards TRKA, ALK and ALK, respectively. Compared with Entrectinib, compound 21 not only ensured the inhibitory activity on TRKA, but also improved the affinity with ALK and ALK to a certain extent. Ultimately, the binding model of 21 with TRKA and ALK were ideally established through molecular docking, which further confirmed the SARs analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116396DOI Listing
September 2021

Dynamics of the Upper Respiratory Tract Microbiota and its Association with Mortality in COVID-19.

Am J Respir Crit Care Med 2021 Sep 17. Epub 2021 Sep 17.

Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;

Rationale: Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear.

Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods:We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients.

Measurements And Main Results: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). Conclusions:URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202103-0814OCDOI Listing
September 2021

PlantGSAD: a comprehensive gene set annotation database for plant species.

Nucleic Acids Res 2021 Sep 17. Epub 2021 Sep 17.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab794DOI Listing
September 2021

Lymph-Node-Targeted Cholesterolized TLR7 Agonist Liposomes Provoke a Safe and Durable Antitumor Response.

Nano Lett 2021 Sep 17. Epub 2021 Sep 17.

Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan 610041, PR China.

Toll-like receptor (TLR) agonists as the potent stimulants of an innate immune system hold promises for applications in anticancer immunotherapy. However, most of them are limited in the clinical translation due to the uncontrolled systemic inflammatory response. In the current study, 1V209, a small molecule TLR7 agonist, was conjugated with cholesterol (1V209-Cho) and prepared into liposomes (1V209-Cho-Lip). 1V209-Cho-Lip exerted minimal toxic effects and enhanced the transportation ability in lymph nodes (LNs) compared with 1V209. 1V209-Cho-Lip treatment inhibited tumor progression in CT26 colorectal cancer, 4T1 breast cancer, and Pan02 pancreatic ductal cancer models through inducing effective DC activation and eliciting CD8 T cell responses. Furthermore, 1V209-Cho-Lip induced tumor-specific memory immunity to inhibit cancer recurrence and metastasis. These results indicate that cholesterol conjugation with 1V209 is an effective approach to target lymph nodes and to reduce the adverse effects. This work provides a rational basis for the distribution optimization of TLR agonists for potential clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.nanolett.1c01968DOI Listing
September 2021
-->