Publications by authors named "Chao Yan"

577 Publications

The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer.

Redox Biol 2021 Jul 20;46:102076. Epub 2021 Jul 20.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Acquired resistance to tyrosine kinase inhibitors (TKIs) is the major obstacle to improve clinical efficacy in cancer patients. The epithelial-stromal interaction in tumor microenvironment influences cancer drug response to TKIs. Anlotinib is a novel oral multi-targeted TKI, and has recently been proven to be effective and safe for several tumors. However, if and how the epithelial-stromal interaction in tumor microenvironment affects anlotinib response in gastric cancer (GC) is not known. In this study, we found that anlotinib inhibited GC cells growth by inducing GC cells apoptosis and G2/M phase arrest in a dose- and time-dependent manner. Reactive oxygen species (ROS) mediated anlotinib-induced apoptosis in GC cells, while cancer-associated fibroblasts (CAFs) significantly suppressed anlotinib-induced apoptosis and ROS in GC cells. Increased BDNF that was derived from CAFs activated TrkB-Nrf2 signaling in GC cells, and reduced GC cells response to anlotinib. We identified secreted lactate from GC cells as the key molecule instructing CAFs to produce BDNF in a NF-κB-dependent manner. Additionally, functional targeting BDNF-TrkB pathway with neutralizing antibodies against BDNF and TrkB increased the sensitivity of GC cells towards anlotinib in human patient-derived organoid (PDO) model. Taken together, these results characterize a critical role of the epithelial-stroma interaction mediated by the lactate/BDNF/TrkB signaling in GC anlotinib resistance, and provide a novel option to overcome drug resistance.
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http://dx.doi.org/10.1016/j.redox.2021.102076DOI Listing
July 2021

Sexual dysfunction in patients with myasthenia gravis.

J Neuroimmunol 2021 Jul 20;358:577669. Epub 2021 Jul 20.

Department of Neurology, West China Hospital, Sichuan University, Guo Xuexiang #37, Chengdu 610041, China. Electronic address:

Background: Myasthenia gravis (MG) is an autoimmune disease that causes fatigueable muscle weakness. Sexual dysfunction (SD) is a common condition, but the association between SD and MG remains poorly understood.

Methods: An observational study was conducted to explore SD incidence and risk factors in MG patients. The study enrolled 158 MG patients and 161 age- and sex-matched healthy individuals. SD was investigated using the Female Sexual Function Inventory (FSFI), the abridged International Index of Erectile Function-5 (IIEF-5), and the Chinese Index of Premature Ejaculation-5 (CIPE-5). The mental health was evaluated using Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).

Results: A total of 52 male patients and 106 female patients were finally included. The average age of these patients was 41.82 ± 10.44 years. The incidence of female SD was significantly higher in MG patients (48.11%) than in healthy people (22.64%) (P < 0.001). The incidence of SD in male MG patients was also higher. Age and depression were significantly correlated with decreased libido, wakefulness, lubrication, orgasm, and satisfaction scores, indicating that these are risk factors for SD. Age (OR:1.13, CI%:1.06-1.21, P < 0.001) and HAMD scores (OR:1.53, CI%:1.0-2.13, P = 0.011) are independent risk factors for SD of MG patients.

Conclusion: SD is a common problem in MG, and its severity does not change with the severity of the disease. Age and depression are risk factors for sexual dysfunction.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577669DOI Listing
July 2021

Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis.

J Immunol Res 2021 8;2021:1815098. Epub 2021 Jul 8.

Center for Hypertension Care, Shanxi Medical University First Hospital, Taiyuan, Shanxi 030001, China.

Adiponectin is a small peptide secreted and a key component of the endocrine system and immune system. Although globular adiponectin protects myocardial ischemia/reperfusion-induced cardiomyocyte injury, the protective mechanisms remain largely unresolved. Using a neonatal rat ventricular myocyte hypoxia/reoxygenation model, we investigated the role of its potential mechanisms of necroptosis in globular adiponectin-mediated protection in hypoxia/reoxygenation-induced cardiomyocyte injury as compared to apoptosis. We found that globular adiponectin treatment attenuated cardiomyocyte injury as indicated by increased cell viability and reduced lactate dehydrogenase release following hypoxia/reoxygenation. Immunofluorescence staining and Western blotting demonstrated that both necroptosis and apoptosis were triggered by hypoxia/reoxygenation and diminished by globular adiponectin. Necrostatin-1 (RIP1-specific inhibitor) and Z-VAD-FMK (pan-caspase inhibitor) only mimicked the inhibition of necroptosis and apoptosis, respectively, by globular adiponectin in hypoxia/reoxygenation-treated cardiomyocytes. Globular adiponectin attenuated reactive oxygen species production, oxidative damage, and p38MAPK and NF-B signaling, all important for necroptosis and apoptosis. Collectively, our study suggests that globular adiponectin inhibits hypoxia/reoxygenation-induced necroptosis and apoptosis in cardiomyocytes probably by reducing oxidative stress and interrupting p38MAPK signaling.
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http://dx.doi.org/10.1155/2021/1815098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282401PMC
July 2021

Sequential multiple mediation of cognitive fusion and experiential avoidance in the relationship between rumination and social anxiety among Chinese adolescents.

Anxiety Stress Coping 2021 Jul 21:1-11. Epub 2021 Jul 21.

Shanghai Changning Mental Health Center, Shanghai, People's Republic of China.

Background And Objectives: The potential mechanism by which rumination influences social anxiety through cognitive fusion and experiential avoidance proposed by the Acceptance and Commitment Therapy model has not been well-documented. This study, therefore, aimed to examine the sequential multiple mediation of the two processes.

Design: A cross-sectional survey was conducted.

Method: A total of 233 Chinese adolescents (42.06% girls) completed a set of printed self-report questionnaires measuring rumination, cognitive fusion, experiential avoidance, and social anxiety. The SPSS macro PROCESS (model 6) was used to test a sequential mediating model. A 95% confidence interval (CI) was calculated with 5000 bootstrapping re-samples.

Results: Bootstrap analyses indicated that there were indirect effects of rumination on social anxiety mediated by cognitive fusion together with experiential avoidance ( = 0.098, BootSE = 0.032, CI = 0.045 to 0.170), or solely by experiential avoidance ( = 0.048, BootSE = 0.020, CI = 0.014 to 0.093). The mediation of cognitive fusion alone was not significant ( = 0.065, BootSE = 0.038, CI = -0.006 to 0.144).

Conclusions: The results indicated the sequential mediating role of cognitive fusion and experiential avoidance, and the relative prominence of the latter in the association between rumination and social anxiety.
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http://dx.doi.org/10.1080/10615806.2021.1955864DOI Listing
July 2021

Comparative Performance of Four Nucleic Acid Amplification Tests for SARS-CoV-2 Virus.

Clin Lab 2021 Jul;67(7)

Background: COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was discovered in 2019 and spread around the world in a short time. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing of COVID-19. Aim of this study was to evaluate the performance of four NAAT assays.

Methods: Limit of detection (LOD), precision, accuracy, analytical specificity and analytical interference studies on four NAATs (Daan, Sansure, Hybribio, and Bioperfectus) were performed according to Clinical Laboratory Standards Institute protocols and guidelines. The four NAATs were compared using 46 clinical samples.

Results: The LOD of the N gene for Daan, Sansure, and Hybribio was 500 copies/mL, and that for Bioperfectus was 1,000 copies/mL. The LOD of the ORF1ab gene for Daan, Bioperfectus, and Hybribio was 3,000 copies/mL, and that for Sansure was 2,000 copies/mL. A good precision was shown at the concentration above 20% of the LOD for all four NAATs, with all individual coefficients of variation below 3.6%. Satisfactory results were also observed in the accuracy, analytical specificity, and analytical interference tests. The results of the comparison test showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16/16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity of 81.25% (13/16). However, no significant difference in sensitivity was found between Bioperfectus NAAT and the three other NAATs (p > 0.05).

Conclusions: The four SARS-CoV-2 NAATs showed comparable performance, with the LOD of the N gene lower than the LOD of the ORF1ab gene.
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http://dx.doi.org/10.7754/Clin.Lab.2020.201025DOI Listing
July 2021

[High-efficiency separation and analysis of monosaccharides in Pueraria polysaccharides by pressurized capillary electrochromatography].

Se Pu 2020 Nov;38(11):1323-1331

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Pueraria polysaccharides have been proven to possess biological activities such as bacteriostasis, anti-oxidative, anti-tumor, and immunity boosting activities. The variation in the structure, composition, and amount of monosaccharides in these polysaccharides may lead to different spatial structures and biological activities. Therefore, extraction of Pueraria polysaccharides and determination of the monosaccharide composition are of great significance for activity analysis and quality control. Direct detection of saccharides is difficult because they are strongly polar and do not show absorption in the ultraviolet region. At present, the commonly used methods for saccharide detection are liquid chromatography-ultraviolet detection, gas chromatography-ultraviolet detection, and mass spectrometry. Pressurized capillary electrochromatography is a high-efficiency microseparation technology. In this study, two kinds of Pueraria polysaccharides were extracted by an ultrasonic-assisted method, and response surface methodology was performed to explore the conditions for ultrasonic-assisted extraction of polysaccharides from Pueraria. The interaction effects of four factors, the liquid-solid ratio, ultrasonic extraction time, ultrasonic extraction temperature, and ultrasonic power, on the extraction rate of the polysaccharides were analyzed. By combining the optimal conditions predicted by the software and the actual equipment conditions, the optimal extraction conditions for Pueraria polysaccharides were chosen as follows:ultrasonic extraction temperature, 90℃; liquid-solid ratio of , 20 mL/g; liquid-solid ratio of Pueraria lobata Ohwi, 40 mL/g; ultrasonic extraction time, 30 min; ultrasonic power, 180 W. Through data fitting, the multiple quadratic regression equation of the four factors on the extraction rate of Pueraria polysaccharides was established. A novel method based on pressurized capillary electrochromatography for the separation and analysis of eight neutral monosaccharides has been established. The monosaccharides were derivatized by the 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization method. The separation conditions for these monosaccharides were explored, and the buffer concentration, buffer pH, applied voltage, type of chromatographic column, and mobile phase ratio were optimized. Finally, the established pressurized capillary electrochromatography-ultraviolet detection method was applied to the detection and identification of two kinds of actual Pueraria polysaccharide samples. The results of response surface analysis showed that among the four experimental factors, ultrasonic extraction temperature had the greatest influence on the extraction rate of polysaccharides from the two kinds of Pueraria, followed by the liquid-solid ratio; the influence of the ultrasonic extraction time and ultrasonic power was relatively weak. The experimental conditions were determined as follows:the separation of eight neutral monosaccharide derivatives could be realized within 24 min on a Halo-2.7 μm core-shell C18 capillary column with acetonitrile-50 mmol/L ammonium acetate aqueous solution (18:82, v/v, pH 4.1) as the mobile phase, by detection at 250 nm under an applied voltage of-20 kV. The separation and detection speeds and the column efficiency achieved with this method were much better than those obtained with the traditional liquid chromatography method. The results show that the proposed method has a good linear relationship and good repeatability. The separation and identification results for the actual samples showed that the polysaccharides of were mainly composed of glucose, mannose, rhamnose, and fucose in the molar ratio 1.00:0.16:0.14:0.07. The polysaccharides of were mainly composed of glucose and mannose in the molar ratio 1.00:0.70. This study provides a novel method for the rapid and efficient separation and detection of neutral monosaccharides, and serves as a reference for analyzing the monosaccharide composition of Pueraria polysaccharides.
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http://dx.doi.org/10.3724/SP.J.1123.2020.01005DOI Listing
November 2020

Transcriptome and Degradome Profiling Reveals a Role of miR530 in the Circadian Regulation of Gene Expression in .

Cells 2021 Jun 17;10(6). Epub 2021 Jun 17.

State Key Laboratory of Tree Genetics and Breeding, Research Institute of Subtropical Forestry, Chinese Academy of Forestry, Hangzhou 311400, China.

Crassulacean acid metabolism (CAM) is an important photosynthetic pathway for plant adaptation to dry environments. CAM plants feature a coordinated interaction between mesophyll and epidermis functions that involves refined regulations of gene expression. Plant microRNAs (miRNAs) are crucial post-transcription regulators of gene expression, however, their roles underlying the CAM pathway remain poorly investigated. Here, we present a study characterizing the expression of miRNAs in an obligate CAM species . Through sequencing of transcriptome and degradome in mesophyll and epidermal tissues under the drought treatments, we identified differentially expressed miRNAs that were potentially involved in the regulation of CAM. In total, we obtained 84 miRNA genes, and eight of them were determined to be -specific miRNAs. It is widely accepted that CAM pathway is regulated by circadian clock. We showed that miR530 was substantially downregulated in epidermal peels under drought conditions; miR530 targeted two tandem zinc knuckle/PLU3 domain encoding genes (TZPs) that were potentially involved in light signaling and circadian clock pathways. Our work suggests that the miR530-TZPs module might play a role of regulating CAM-related gene expression in .
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http://dx.doi.org/10.3390/cells10061526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233840PMC
June 2021

A Novel Inflammatory-Nutritional Prognostic Scoring System for Stage III Gastric Cancer Patients With Radical Gastrectomy Followed by Adjuvant Chemotherapy.

Front Oncol 2021 14;11:650562. Epub 2021 Jun 14.

Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: The present study was designed to explore the prognostic value of preoperative inflammatory and nutritional biomarkers in stage III gastric cancer (GC) patients with adjuvant chemotherapy and to develop a novel scoring system called the inflammatory-nutritional prognostic score (INPS).

Methods: A total of 513 patients with pathological stage III GC undergoing radical gastrectomy followed by adjuvant chemotherapy from 2010 to 2017 were enrolled in the study. Clinicopathological characteristics and blood test parameters of individual patients were collected. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used for feature selection to construct INPS. Survival curves were generated using the Kaplan-Meier method with log-rank tests. The nomogram was generated based on the result of the multivariate analysis using Cox's proportional hazards model. The model was assessed by the concordance index (C-index) and was internally validated by bootstraps.

Results: According to the results of Lasso Cox regression and K-M survival curves, INPS was determined as follows: a low body mass index (BMI) (<23 kg/m), a low prealbumin (<180 mg/L), a high neutrophil-lymphocyte ratio (NLR) (≥2.7), a high platelet-lymphocyte ratio (PLR) (≥209.4), a low lymphocyte-monocyte ratio (LMR) (<2.8), and a low prognostic nutritional index (PNI) (<45.1); each were scored as 1, and the remaining values were scored as 0. The individual scores were then summed up to construct the INPS and further divided into 4 groups: Low Risk (INPS 0); Low-medium Risk (INPS 1); High-medium Risk (INPS 2-4); and High Risk (INPS 5-6). In multivariate analysis, INPS was an independent predictor of overall survival (OS) in stage III GC, with the 5-year OS rates of 70.8%, 57.4%, 41.5%, and 30.6%, respectively. The nomogram based on INPS and other independent predictors (gender, pT stage, pN stage, lymphovascular invasion, and CEA level) showed good predicting performance with a C-index of 0.707, which was superior to the TNM stage alone (C-index 0.645, =0.008) and was internally validated with the corrected C-index of 0.693.

Conclusion: Preoperative INPS was an independent prognostic factor of stage III GC patients with radical surgery followed by adjuvant chemotherapy. The nomogram based on INPS may serve as a simple and potential model in risk stratification and guiding treatment strategies in clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.650562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238197PMC
June 2021

MicroRNA-133a Regulates the Viability and Differentiation Fate of Bone Marrow Mesenchymal Stem Cells via MAPK/ERK Signaling Pathway by Targeting FGFR1.

DNA Cell Biol 2021 Jun 24. Epub 2021 Jun 24.

Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Dysfunction of bone marrow mesenchymal stem cells (BMSCs) is recognized critical in bone deteriorations of osteoporosis. However, the specific mechanisms that determine the fate of BMSCs remain elusive. MicroRNA-133a (miR-133a), a highly conserved microRNA, was investigated under both and conditions. In the study, cell proliferation, cell apoptosis, and osteoblast/adipocyte differentiation of BMSCs as a result of overexpression or knockdown of miR-133a was investigated. In the study, the ovariectomy (OVX) model was applied on mice, with further treatment of the models with BMSC-specific miR-133a antagomir through femur intramedullary injection. Microcomputed tomography scanning and histological analysis of the proximal and middle femur were performed to evaluate the morphological changes. The results revealed that overexpression of miR-133a suppressed cell proliferation, cell viability, and osteoblast differentiation of BMSCs, but increased adipocyte differentiation. We also found that FGFR1, an important upstream regulator of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signal pathway, was a major target of miR-133a. We also recorded that BMSC-specific knockdown of miR-133a attenuates bone loss in OVX mice. Our study suggested that miR-133a played an important role in maintaining the viability and balance between osteoblast and adipocyte differentiation of BMSCs through the MAPK/ERK signaling pathway by targeting FGFR1.
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http://dx.doi.org/10.1089/dna.2021.0206DOI Listing
June 2021

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data.

EBioMedicine 2021 Jul 19;69:103436. Epub 2021 Jun 19.

Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address:

Background: Due to the molecular mechanism complexity and heterogeneity of gastric cancer (GC), mechanistically interpretable biomarkers were required for predicting prognosis and discovering therapeutic targets for GC patients.

Methods: Based on a total of 824 GC-specific fitness genes from the Project Score database, LASSOCox regression was performed in TCGA-STAD cohort to construct a GC Prognostic (GCP) model which was then evaluated on 7 independent GC datasets. Targets prioritization was performed in GC organoids. ARGLU1 was selected to further explore the biological function and molecular mechanism. We evaluated the potential of ARGLU1 serving as a promising therapeutic target for GC using patients derived xenograft (PDX) model.

Findings: The 9-gene GCP model showed a statistically significant prognostic performance for GC patients in 7 validation cohorts. Perturbation of SSX4, DDX24, ARGLU1 and TTF2 inhibited GC organoids tumor growth. The results of tissue microarray indicated lower expression of ARGLU1 was correlated with advanced TNM stage and worse overall survival. Over-expression ARGLU1 significantly inhibited GC cells viability in vitro and in vivo. ARGLU1 could enhance the transcriptional level of mismatch repair genes including MLH3, MSH2, MSH3 and MSH6 by potentiating the recruitment of SP1 and YY1 on their promoters. Moreover, inducing ARGLU1 by LNP-formulated saRNA significantly inhibited tumor growth in PDX model.

Interpretation: Based on genome-wide functional screening data, we constructed a 9-gene GCP model with satisfactory predictive accuracy and mechanistic interpretability. Out of nine prognostic genes, ARGLU1 was verified to be a potential therapeutic target for GC.

Funding: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/j.ebiom.2021.103436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220577PMC
July 2021

MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3β/β-catenin signalling.

J Cell Mol Med 2021 Jul 13;25(14):7013-7027. Epub 2021 Jun 13.

Department of Respiratory and Critical Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Recent studies have demonstrated that one-carbon metabolism plays a significant role in cancer development. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme of one-carbon metabolism, has been reported to be dysregulated in many cancers. However, the specific role and mechanism of MTHFD2 in lung adenocarcinoma (LUAD) still remains unclear. In this study, we evaluated the clinicopathological and prognostic values of MTHFD2 in LUAD patients. We conducted a series of functional experiments in vivo and in vitro to explore novel mechanism of MTHFD2 in LUAD. The results showed that MTHFD2 was significantly up-regulated in LUAD tissues and predicted poor prognosis of LUAD patients. Knockdown of MTHFD2 dramatically inhibited cell proliferation and migration by blocking the cell cycle and inducing the epithelial-mesenchymal transition (EMT). In addition, MTHFD2 knockdown suppressed LUAD growth and metastasis in cell-derived xenografts. Mechanically, we found that MTHFD2 promoted LUAD cell growth and metastasis via AKT/GSK-3β/β-catenin signalling. Finally, we identified miR-30a-3p as a novel regulator of MTHFD2 in LUAD. Collectively, MTHFD2 plays an oncogenic role in LUAD progression and is a promising target for LUAD diagnosis and therapy.
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http://dx.doi.org/10.1111/jcmm.16715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278097PMC
July 2021

Nitrate Transport and Distribution in Soybean Plants With Dual-Root Systems.

Front Plant Sci 2021 20;12:661054. Epub 2021 May 20.

College of Agriculture, Northeast Agricultural University, Harbin, China.

Nitrate absorbed by soybean ( L. Merr.) roots from the soil can promote plant growth, while nitrate transported to nodules inhibits nodulation and nodule nitrogen fixation activity. The aim of this study was to provide new insights into the inhibition of nodule nitrogen (N) fixation by characterizing the transport and distribution of nitrate in soybean plants. In this research, pot culture experiments were conducted using a dual root system of soybeans. In the first experiment, the distribution of N derived from nitrate was observed. In the second experiment, nitrate was supplied-withdrawal-resupplied to one side of dual-root system for nine consecutive days, and the other side was supplied with N-free solution. Nitrate contents in leaves, stems, petioles, the basal root of pealed skin and woody part at the grafting site were measured. Nitrate transport and distribution in soybean were analyzed combining the results of two experiments. The results showed that nitrate supplied to the N-supply side of the dual-root system was transported to the shoots immediately through the basal root pealed skin (the main transport route was via the phloem) and woody part (transport was chiefly related to the xylem). There was a transient storage of nitrate in the stems. After the distribution of nitrate, a proportion of the nitrate absorbed by the roots on the N-supply side was translocated to the roots and nodules on the N-free side with a combination of the basal root pealed skin and woody part. In conclusion, the basal root pealed skin and woody part are the main transport routes for nitrate up and down in soybean plants. Nitrate absorbed by roots can be transported to the shoots and then retranslocated to the roots again. The transport flux of nitrate to the N-free side was regulated by transient storage of nitrate in the stems.
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http://dx.doi.org/10.3389/fpls.2021.661054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174562PMC
May 2021

Dual-Energy Computed Tomography-Based Radiomics to Predict Peritoneal Metastasis in Gastric Cancer.

Front Oncol 2021 14;11:659981. Epub 2021 May 14.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To develop and validate a dual-energy computed tomography (DECT) derived radiomics model to predict peritoneal metastasis (PM) in patients with gastric cancer (GC).

Methods: This retrospective study recruited 239 GC (non-PM = 174, PM = 65) patients with histopathological confirmation for peritoneal status from January 2015 to December 2019. All patients were randomly divided into a training cohort (n = 160) and a testing cohort (n = 79). Standardized iodine-uptake (IU) images and 120-kV-equivalent mixed images (simulating conventional CT images) from portal-venous and delayed phases were used for analysis. Two regions of interest (ROIs) including the peritoneal area and the primary tumor were independently delineated. Subsequently, 1691 and 1226 radiomics features were extracted from the peritoneal area and the primary tumor from IU and mixed images on each phase. Boruta and Spearman correlation analysis were used for feature selection. Three radiomics models were established, including the R_IU model for IU images, the R_MIX model for mixed images and the combined radiomics model (the R_comb model). Random forest was used to tune the optimal radiomics model. The performance of the clinical model and human experts to assess PM was also recorded.

Results: Fourteen and three radiomics features with low redundancy and high importance were extracted from the IU and mixed images, respectively. The R_IU model showed significantly better performance to predict PM than the R_MIX model in the training cohort (AUC, 0.981 vs. 0.917, p = 0.034). No improvement was observed in the R_comb model (AUC = 0.967). The R_IU model was the optimal radiomics model which showed no overfitting in the testing cohort (AUC = 0.967, p = 0.528). The R_IU model demonstrated significantly higher predictive value on peritoneal status than the clinical model and human experts in the testing cohort (AUC, 0.785, p = 0.005; AUC, 0.732, p <0.001, respectively).

Conclusion: DECT derived radiomics could serve as a non-invasive and easy-to-use biomarker to preoperatively predict PM for GC, providing opportunity for those patients to tailor appropriate treatment.
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http://dx.doi.org/10.3389/fonc.2021.659981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160383PMC
May 2021

The Relationship Between Lower Respiratory Tract Microbiome and Allergic Respiratory Tract Diseases in Children.

Front Microbiol 2021 14;12:630345. Epub 2021 May 14.

Capital Institute of Pediatrics, Beijing, China.

Similar to those in the upper respiratory tract, there are microbes present in the healthy human lower respiratory tract (LRT), including the lungs and bronchus. To evaluate the relationship between LRT microbiome and allergic respiratory diseases in children, we enrolled 68 children who underwent bronchoscopy from January 2018 to December 2018 in the affiliated hospital of the Capital Institute of Pediatrics. Using the total IgE (TIgE) values, children were divided into two groups: allergy sensitivity (AS) group and non-allergy sensitivity (NAS) group. Nucleic acid was extracted from samples of bronchoalveolar lavage fluid (BALF) from the two groups of children taken during bronchoscopy treatment and the 16S rDNA gene was sequenced and analyzed. The results showed that , , , , , and were detected in all patients. There was a statistically significant difference in the composition and distribution of microbiota between the AS and NAS groups ( < 0.01). Analysis of the correlation of clinical indices and microbiome showed that TIgE was positively correlated with and negatively correlated with . Absolute lymphocyte count showed a relationship with , and the absolute neutrophil count or percentage of neutrophils showed a relationship with . The LRT microbiome functioned similarly to the intestinal microbiome. That is, the decrease in microbial diversity and the change in composition could lead to an increase in allergic symptoms. The microbiome of the LRT in children, especially that of and , showed a correlation with respiratory allergic diseases.
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http://dx.doi.org/10.3389/fmicb.2021.630345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160472PMC
May 2021

Recent progress of personal glucose meters integrated methods in food safety hazards detection.

Crit Rev Food Sci Nutr 2021 May 28:1-14. Epub 2021 May 28.

Engineering Research Center of Bio-Process, MOE, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.

Development of personal glucose meters (PGMs) for blood glucose monitoring and management by the diabetic patients has been a long history since its first invention in 1968 and commercial application in 1975. The main reasons for its wide acceptance and popularity can be attributed mainly to the easy operation, test-to-result model, low cost, and small volume of sample required for blood glucose concentration test. During past decades, advances in analytical techniques have repurposed the use of PGMs into a general point-of-care testing platform for a variety of non-glucose targets, especially the food hazards. In this review, we summarized the recent published research using PGMs to detect the food safety hazards of mycotoxins, illegal additives, pathogen bacteria, and pesticide and veterinary drug residues detection with PGMs. The progress on PGM-based detection achieved in food safety have been carefully compared and analyzed. Furthermore, the current bottlenecks and challenges for practical applications of PGM for hazards detection in food safety have also been proposed.
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http://dx.doi.org/10.1080/10408398.2021.1913990DOI Listing
May 2021

A randomized controlled trial to evaluate omentum-preserving gastrectomy for patients with T1-T3 gastric cancer.

Future Oncol 2021 May 19. Epub 2021 May 19.

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.

Although complete omentectomy is traditionally performed in patients with gastric cancer as part of radical gastrectomy to ensure the elimination of micrometastases, the prognostic value of omentectomy during gastrectomy remains unclear. Retrospective studies have shown that the incidence of metastases in the greater omentum is very low in T1-T3 gastric cancer. Thus radical gastrectomy with D2 lymphadenectomy and preservation of the greater omentum may be a proper curative treatment for gastric cancer patients with T1-T3 tumors. The aim of this article is to describe the design and rationale for this prospective, randomized controlled DRAGON-05 trial, conducted to evaluate the prognostic value of omentum-preserving gastrectomy for patients with T1-T3 gastric cancer. ChiCTR2000040045 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2021-0240DOI Listing
May 2021

Culture, Sex, and Group-Bias in Trait and State Empathy.

Front Psychol 2021 28;12:561930. Epub 2021 Apr 28.

School of Applied Psychology, Griffith University, Gold Coast, QLD, Australia.

Empathy is sharing and understanding others' emotions. Recently, researchers identified a culture-sex interaction effect in empathy. This phenomenon has been largely ignored by previous researchers. In this study, the culture-sex interaction effect was explored with a cohort of 129 participants (61 Australian Caucasians and 68 Chinese Hans) using both self-report questionnaires (i.e., Empathy Quotient and Interpersonal Reactivity Index) and computer-based empathy tasks. In line with the previous findings, the culture-sex interaction effect was observed for both trait empathy (i.e., the generalized characteristics of empathy, as examined by the self-report questionnaires) and state empathy (i.e., the on-spot reaction of empathy for a specific stimulus, as evaluated by the computer-based tasks). Moreover, in terms of state empathy, the culture-sex interaction effect further interacted with stimulus traits (i.e., stimulus ethnicity, stimulus sex, or stimulus emotion) and resulted in three- and four-way interactions. Follow-up analyses of these higher-order interactions suggested that the phenomena of ethnic group bias and sex group favor in empathy varied among the four culture-sex participant groups (i.e., Australian female, Australian male, Chinese female, and Chinese male). The current findings highlighted the dynamic nature of empathy (i.e., its sensitivity toward both participant traits and stimulus features). Furthermore, the newly identified interaction effects in empathy deserve more investigation and need to be verified with other Western and Asian populations.
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http://dx.doi.org/10.3389/fpsyg.2021.561930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113867PMC
April 2021

Toward Building a Physical Proxy for Gas-Phase Sulfuric Acid Concentration Based on Its Budget Analysis in Polluted Yangtze River Delta, East China.

Environ Sci Technol 2021 05 7;55(10):6665-6676. Epub 2021 May 7.

Joint International Research Laboratory of Atmospheric and Earth System Sciences, School of Atmospheric Sciences, Nanjing University, Nanjing 210023, China.

Gaseous sulfuric acid (HSO) is a crucial precursor for secondary aerosol formation, particularly for new particle formation (NPF) that plays an essential role in the global number budget of aerosol particles and cloud condensation nuclei. Due to technology challenges, global-wide and long-term measurements of gaseous HSO are currently very challenging. Empirical proxies for HSO have been derived mainly based on short-term intensive campaigns. In this work, we performed comprehensive measurements of HSO and related parameters in the polluted Yangtze River Delta in East China during four seasons and developed a physical proxy based on the budget analysis of gaseous HSO. Besides the photo-oxidation of SO, we found that primary emissions can contribute considerably, particularly at night. Dry deposition has the potential to be a non-negligible sink, in addition to condensation onto particle surfaces. Compared with the empirical proxies, the newly developed physical proxy demonstrates extraordinary stability in all the seasons and has the potential to be widely used to improve the understanding of global NPF fundamentally.
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http://dx.doi.org/10.1021/acs.est.1c00738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154357PMC
May 2021

Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy.

Front Oncol 2021 15;11:607640. Epub 2021 Apr 15.

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC.

Methods: A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups.

Results: Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively.

Conclusions: We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.
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http://dx.doi.org/10.3389/fonc.2021.607640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082104PMC
April 2021

Generating Electronic Health Records with Multiple Data Types and Constraints.

AMIA Annu Symp Proc 2020 25;2020:1335-1344. Epub 2021 Jan 25.

Vanderbilt University, Nashville, TN.

Sharing electronic health records (EHRs) on a large scale may lead to privacy intrusions. Recent research has shown that risks may be mitigated by simulating EHRs through generative adversarial network (GAN) frameworks. Yet the methods developed to date are limited because they 1) focus on generating data of a single type (e.g., diagnosis codes), neglecting other data types (e.g., demographics, procedures or vital signs), and 2) do not represent constraints betweenfeatures. In this paper, we introduce a method to simulate EHRs composed of multiple data types by 1) refining the GAN model, 2) accounting for feature constraints, and 3) incorporating key utility measures for such generation tasks. Our analysis with over 770,000 EHRs from Vanderbilt University Medical Center demonstrates that the new model achieves higher performance in terms ofretaining basic statistics, cross-feature correlations, latent structural properties, feature constraints and associated patterns from real data, without sacrificing privacy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075510PMC
July 2021

Identification of novel autoantibodies in ascites of relapsed paclitaxel-resistant gastric cancer with peritoneal metastasis using immunome protein microarrays and proteomics.

Cancer Biomark 2021 ;31(4):329-338

Background: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance.

Objective: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis.

Methods: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected.

Results: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays.

Conclusions: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance.
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http://dx.doi.org/10.3233/CBM-203142DOI Listing
January 2021

Prediction model of objective response after neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

Am J Transl Res 2021 15;13(3):1568-1579. Epub 2021 Mar 15.

Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.

Background: Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (LAGC). However, the response of LAGC after NAC varies among different patients. The objective response after NAC has proven to be an excellent indicator for benefiting from NAC, yet effective predictors of objective response are still lacking. The present study aimed to identify potential predictors of objective response in LAGC patients treated with NAC.

Methods: Clinicopathological data from 267 patients with LAGC who received NAC and met the inclusion criteria between July 2009 and December 2018 were retrospectively reviewed. Patients were randomly divided into the training and test sets at a 2:1 ratio. Univariate analysis was used to investigate whether any factors were correlated with objective response in the training set. Multivariate logistic regression analysis was applied to find independent predictors. A risk score model was then constructed based on the independent predictors, and its performance in predicting objective response was validated in the test set.

Results: Univariate analysis found that gender, age, short axis diameter of the largest regional lymph node (LN), serum total protein content, CEA detection value, tumor location, tumor differentiation, signet ring cell carcinoma component and Borrmann type were potential predictors for objective response. In multivariate logistic regression analysis, gender, LN and signet ring cell carcinoma component were independent predictors for objective response. Based on independent predictors, we developed a prediction model for objective response.

Conclusions: We found gender, LN and signet ring cell carcinoma component were independent predictors for objective response. The prediction model is a good tool to predict the objective response for LAGC patients treated with NAC, which can be applied to guide clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014384PMC
March 2021

Increasing Walking Speed to Achieve a Pre-training Endurance Shuttle Walk Time of 5-10 min May Improve Test Responsiveness in People With Chronic Obstructive Pulmonary Disease.

J Cardiopulm Rehabil Prev 2021 Jul;41(4):264-266

School of Physiotherapy and Exercise Science, Faculty of Health Sciences, Curtin University, Western Australia, Australia (Drs Hill, Cavalheri, Ng, S. C. Jenkins, and Eastwood and Ms Chao); Institute for Respiratory Health, Western Australia, Australia (Drs Hill, Cavalheri, S. C. Jenkins, and Eastwood and Ms Cecins); Physiotherapy Department, Singapore General Hospital, Singapore (Ms Chao and Dr Ng); Allied Health, South Metropolitan Health Service, Perth, Western Australia, Australia (Dr Cavalheri); Discipline of Physiotherapy, The University of Sydney, New South Wales, Australia (Drs Wootton, McKeough, and Alison); Chronic Disease Community Rehabilitation Service, Northern Sydney Local Health District, New South Wales, Australia (Dr Wootton); Departments of Physiotherapy (Dr S. C. Jenkins and Ms Cecins) and Pulmonary Physiology & Sleep Medicine (Drs Eastwood and Hillman), Sir Charles Gairdner Hospital, Western Australia, Australia; Centre for Sleep Science, School of Human Sciences, The University of Western Australia, Western Australia, Australia (Drs Eastwood and Hillman); Department of Thoracic Medicine, Concord Hospital, New South Wales, Australia (Dr C. Jenkins); and Physiotherapy Department, Sydney Local Health District, Sydney, New South Wales, Australia (Drs Spencer and Alison).

Purpose: The endurance shuttle walk test (ESWT) was used to evaluate ground-based walking training in chronic obstructive pulmonary disease. During pre-training testing, those who walked 5-10 min on the first ESWT with minimal symptoms performed additional ESWTs at increasing speeds until they were at least moderately symptomatic and terminated the test between 5 and 10 min. This report compares participant characteristics and test responsiveness with participants grouped according to whether or not faster walking speeds were selected for the ESWT during pre-training testing.

Methods: We conducted a retrospective analysis of data collected in the intervention group during a randomized controlled trial. The intervention was supervised ground-based walking training, performed two to three times/wk, for 8-10 wk. Prior to and immediately following completion of training, participants completed the 6-min walk test (6MWT), incremental shuttle walk test (ISWT), and ESWT.

Results: Data were available on 77 participants (70 ± 9 yr, forced expiratory volume in the first second of expiration [FEV1] 43 ± 15 % predicted). For those whom a faster speed was selected during the pre-training ESWTs were characterized by milder dyspnea and leg fatigue on completion of the baseline 6MWT and ISWT (P < .05 for all). On training completion, the change in ESWT was greater in those for whom a faster speed was selected (376 ± 344 sec vs 176 ± 274 sec; P = .017).

Conclusions: Participants who report modest symptoms on completion of the pre-training 6MWT or ISWT may achieve a long pre-training ESWT time. In this situation, repeating the pre-training ESWT at a faster walking speed to achieve an exercise time between 5 and 10 min with moderate symptoms may be advantageous.
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http://dx.doi.org/10.1097/HCR.0000000000000575DOI Listing
July 2021

CcBLH6, a bell-like homeodomain-containing transcription factor, regulates the fruit lignification pattern.

Planta 2021 Apr 5;253(5):90. Epub 2021 Apr 5.

State Key Laboratory of Tree Genetics and Breeding, Research Institute of Subtropical Forestry, Chinese Academy of Forestry, Hangzhou, 311400, Zhejiang, China.

Main Conclusion: CcBLH6 is a bell-like homeodomain-containing transcription factor that plays an important role of lignin biosynthesis in the control of fruit lignification pattern in Camellia chekiangoleosa. The fruit of Camellia chekiangoleosa has a unique lignification pattern that features with a thick pericarp containing a low level of lignification. Yet the fruit lignification pattern and the regulatory network of responsible gene transcription are poorly understood. Here, we characterized a bell-like homeodomain-containing (BLH) transcription factor from C. chekiangoleosa, CcBLH6, in the control of fruit lignification. CcBLH6 expression was highly correlated with the unique lignification pattern during fruit development. The ectopic expression of CcBLH6 promoted the lignification process of stem and root in Arabidopsis. We found that expression of genes related to lignin biosynthesis and its transcriptional regulation was altered in transgenic lines. In a Camellia callus-transformation system, overexpression of CcBLH6 greatly enhanced the expression of genes related to lignin biosynthesis and its transcriptional regulation was altered in transgenic lines. In the callus-transformation system, overexpression of CcBLH6 greatly enhanced the lignification of parenchymal cells, and the regulation of several genes involved in lignin accumulation was largely consistent between Arabidopsis and Camellia. Our study reveals a positive role of CcBLH6 in the regulation of lignin biosynthesis during fruit lignification in Camellia.
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http://dx.doi.org/10.1007/s00425-021-03610-7DOI Listing
April 2021

Secondary Production of Gaseous Nitrated Phenols in Polluted Urban Environments.

Environ Sci Technol 2021 04 1;55(8):4410-4419. Epub 2021 Apr 1.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, BIC-ESAT and IJRC, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China.

Nitrated phenols (NPs) are important atmospheric pollutants that affect air quality, radiation, and health. The recent development of the time-of-flight chemical ionization mass spectrometer (ToF-CIMS) allows quantitative online measurements of NPs for a better understanding of their sources and environmental impacts. Herein, we deployed nitrate ions as reagent ions in the ToF-CIMS and quantified six classes of gaseous NPs in Beijing. The concentrations of NPs are in the range of 1 to 520 ng m. Nitrophenol (NPh) has the greatest mean concentration. Dinitrophenol (DNP) shows the greatest haze-to-clean concentration ratio, which may be associated with aqueous production. The high concentrations and distinct diurnal profiles of NPs indicate a strong secondary formation to overweigh losses, driven by high emissions of precursors, strong oxidative capacity, and high NO levels. The budget analysis on the basis of our measurements and box-model calculations suggest a minor role of the photolysis of NPs (<1 ppb h) in producing OH radicals. NPs therefore cannot explain the underestimated OH production in urban environments. Discrepancies between these results and the laboratory measurements of the NP photolysis rates indicate the need for further studies aimed at understanding the production and losses of NPs in polluted urban environments.
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http://dx.doi.org/10.1021/acs.est.0c07988DOI Listing
April 2021

In vivo self-assembled small RNAs as a new generation of RNAi therapeutics.

Cell Res 2021 Jun 29;31(6):631-648. Epub 2021 Mar 29.

Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, Chinese Academy of Medical Sciences Research Unit of Extracellular RNA, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Institute of Artificial Intelligence Biomedicine, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.
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http://dx.doi.org/10.1038/s41422-021-00491-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169669PMC
June 2021

miR-133a silencing rescues glucocorticoid-induced bone loss by regulating the MAPK/ERK signaling pathway.

Stem Cell Res Ther 2021 03 29;12(1):215. Epub 2021 Mar 29.

Department of Orthopedics, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230000, China.

Background: Dysfunction of mesenchymal stem cells (MSCs) is recognized as critical to the pathogenesis of glucocorticoid-induced osteoporosis (GIO), suggesting the potential of MSC-targeting interventions for this disorder. As the miR-133a has been shown to play an important role in bone metabolism, we hypothesized that miR-133a may also be involved in GIO.

Methods: In the in vitro study, we examined the effect of miR-133a antagomir on DEX-treated MSCs, including proliferation, apoptosis, osteoblast, and adipocyte differentiation, then, we explored the mechanism of these effects of miR-133a silencing through measuring the phosphorylation of ERK1/2 and its regulator FGFR1 via western blot and qRT-PCR. In the in vivo study, we developed a GIO rat model by injecting methylprednisolone and modulated the miR-133a expression in the femur by intramedullary injection of the miR-133a antagomir, and then micro-CT analyses and histological staining of the femurs were used to investigate the effect of miR-133a silencing on bone loss of the GIO rats.

Results: qRT-PCR analysis indicated that glucocorticoid induced high miR-133a expression in MSCs and animal models. The in vitro study showed that miR-133a antagomir significantly promoted cell proliferation, viability, and osteoblast differentiation and inhibited adipocyte differentiation in DEX-treated MSCs. Furthermore, the expression of p-ERK1/2 and FGFR1 in DEX-treated MSCs was also upregulated by miR-133a antagomir. Then we investigated the effect of miR-133a silencing on the bone architecture of GIO models, micro-CT analysis showed that miR-133a antagomir attenuated the loss of bone mass and improved the trabecular and cortical parameters induced by methylprednisolone. Histological study showed that miR-133a silencing simultaneously increased bone formation and decreased marrow fat accumulation in GIO rats.

Conclusions: Our findings suggested that miR-133a is strongly associated with GIO and similar disorders induced by glucocorticoids in MSCs. Silencing miR-133a resulted in positive effects on GC-treated MSCs and on bone loss in GIO animal models. Moreover, the FGFR1-MAPK/ERK signaling may be involved in the protective effect of miR-133a silencing.
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http://dx.doi.org/10.1186/s13287-021-02278-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008567PMC
March 2021

Evaluation of the CARDS toxin and its fragment for the serodiagnosis of Mycoplasma pneumoniae infections.

Eur J Clin Microbiol Infect Dis 2021 Aug 18;40(8):1705-1711. Epub 2021 Mar 18.

Department of Bacteriology, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People's Republic of China.

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen in community-acquired pneumonia. The community-acquired respiratory distress syndrome (CARDS) toxin is the only known virulence factor of M. pneumoniae. It is worth exploring whether this toxin can be used as a candidate antigen for the serodiagnosis of M. pneumoniae. In this study, the full-length, N-terminal, and C-terminal regions of the CARDS toxin were expressed and purified, and serological reactions were evaluated using ELISA. A total of 184 serum samples were collected and tested using a commercialized test kit. Eighty-seven samples were positive, and 97 samples were negative for infection. The purified recombinant proteins were used as antigens to test the serum via indirect ELISA. The sensitivity of the CARDS toxin, the N-terminal region, and the C-terminal region were 90.8%, 90.8%, and 92.0%, respectively. The specificity of the CARDS toxin, the N-terminal region, and the C-terminal region were 85.6%, 73.2%, and 93.8%, respectively. All three CARDS toxin proteins exhibited good reactivity, of which the C-terminal region had a good discrimination ability in human sera. This may have a potential diagnostic value for M. pneumoniae infections.
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http://dx.doi.org/10.1007/s10096-021-04209-2DOI Listing
August 2021

Gray Matter Density of the Dorsomedial Prefrontal Cortex Mediates the Relationship Between Catastrophizing and Anxiety in Somatic Symptom Disorder.

Neuropsychiatr Dis Treat 2021 9;17:757-764. Epub 2021 Mar 9.

Department of Psychological Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Objective: Catastrophizing is commonly co-occurrence with anxiety in somatic symptom disorder (SSD). However, the quantitative relationship between catastrophizing and anxiety in SSD and its underlying neuropsychopathology remains unclear.

Methods: To address the issue, twenty-eight SSD patients and twenty-nine healthy controls (HCs) completed the Hamilton anxiety scale and the catastrophizing subscale of the cognitive emotion regulation questionnaire. Then they underwent structural magnetic resonance imaging and voxel-based morphometry analysis was performed to obtain gray matter density (GMD) of the dorsomedial prefrontal cortex (dmPFC).

Results: Independent samples t-tests showed no significance between SSD patients and HCs in the scores on the catastrophizing subscale and GMD of the dmPFC. However, correlation analysis found that catastrophizing was significantly positively associated with anxiety in SSD. Further, mediation analyses revealed that GMD of the dmPFC (bilateral medial Brodmann area 8) mediated the relationship between catastrophizing and anxiety in SSD.

Conclusion: These findings support Kirmayer's disease model of SSD that catastrophic interpretations of somatic symptoms resulted in increased anxiety and demonstrate that the dmPFC may be a potential neural site linking catastrophizing and anxiety in SSD.
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http://dx.doi.org/10.2147/NDT.S296462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955750PMC
March 2021

Time-resolved HO detection with Faraday rotation spectroscopy in a photolysis reactor.

Opt Express 2021 Jan;29(2):2769-2779

Faraday rotation spectroscopy (FRS) employs the Faraday effect to detect Zeeman splitting in the presence of a magnetic field. In this article, we present system design and implementation of radical sensing in a photolysis reactor using FRS. High sensitivity (100 ppb) and time resolved in situ HO detection is enabled with a digitally balanced acquisition scheme. Specific advantages of employing FRS for sensing in such dynamic environments are examined and rigorously compared to the more established conventional laser absorption spectroscopy (LAS). Experimental results show that FRS enables HO detection when LAS is deficient, and FRS compares favorably in terms of precision when LAS is applicable. The immunity of FRS to spectral interferences such as absorption of hydrocarbons and other diamagnetic species absorption and optical fringing are highlighted in comparison to LAS.
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http://dx.doi.org/10.1364/OE.413063DOI Listing
January 2021
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