Publications by authors named "Yang Zhao"

3,300 Publications

  • Page 1 of 1

Corydecumine G Inhibits Microglia Activation via MAPK Pathway in a Rat Model of Neuropathic Pain.

J Chem Neuroanat 2022 Jun 22:102124. Epub 2022 Jun 22.

State Key Laboratory of Natural Medicines and Department of TCM pharmacology, School of Traditional Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China, 211198. Electronic address:

Background And Purpose: Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms.

Experimental Approach: Neuropathic pain was modeled using chronic constriction sciatic nerve injury (CCI) in rats. Western blot, immunofluorescence, and qRT-PCR were used to evaluate the levels of protein and mRNA.

Key Results: Intraperitoneal administration of Cor G concentration-dependently ameliorates mechanical and thermo allodynia, suppresses CCI-induced p38/ERK phosphorylation and spinal cord microglia activation, and attenuates the expression levels of NO, inos, Tnf-α, Pge in dorsal horn of L4-L6 spinal cord on the ligation side in CCI rats. Pretreatment with 30μM Cor G decreased LPS-induced BV2 microglia activation, which occurred via the inos, Tnf-α, Il-1β, Il-6 and phospho-p38/ERK pathways.

Conclusions And Implications: Taken together, we suggest that Cor G, the specific phthalide isoquinoline from traditional Chinese medicine Corydalis Decumbentis Rhizoma, may be promising for treatment of neuropathic pain.
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http://dx.doi.org/10.1016/j.jchemneu.2022.102124DOI Listing
June 2022

Efficacy and Safety of Sintilimab in Combination with Concurrent Chemoradiotherapy for Locally Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (SHARED): Study Protocol of a Prospective, Multi-Center, Single-Arm Phase 2 Trial.

Cancer Manag Res 2022 17;14:2007-2015. Epub 2022 Jun 17.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People's Republic of China.

Purpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116).

Patients And Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored.

Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers.
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http://dx.doi.org/10.2147/CMAR.S355687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211075PMC
June 2022

Lipid Variability and Risk of Cardiovascular Diseases and All-Cause Mortality: A Systematic Review and Meta-Analysis of Cohort Studies.

Nutrients 2022 Jun 13;14(12). Epub 2022 Jun 13.

School of Public Health and Women's Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.

No consensus has yet been reached on the associations of lipid variability (LV) with cardiovascular diseases (CVDs) and all-cause mortality. We aimed to quantify the associations of different types and metrics of LV with CVDs and all-cause mortality. PubMed, Medline, and Embase databases were searched for eligible cohort studies published until 14 December 2021. Lipids included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Metrics of variability included standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM). The primary outcomes were CVDs and all-cause mortality. Random-effects meta-analysis was used to generate a summary of the relative risks (SRRs). Sources of heterogeneity were explored by subgroup analysis and meta-regression. A total of 11 articles based on seven cohorts were included. Participants in the top quartile of TC variability had an increased risk of CVDs (vs. bottom quartile: TC-CV: SRR 1.29, 95% CI 1.15-1.45; TC-SD: 1.28, 1.15-1.43; TC-VIM: 1.26, 1.13-1.41, respectively) and all-cause mortality (vs. bottom quartile: TC-CV: 1.28, 1.15-1.42; TC-SD: 1.32, 1.22-1.44; TC-VIM: 1.32, 1.25-1.40, respectively). Participants in the top quartile of HDL-C variability had an increased risk of CVDs (vs. bottom quartile: HDL-C-CV: 1.11, 1.07-1.15; HDL-C-SD: 1.18, 1.02-1.38; HDL-C-VIM: 1.18, 1.09-1.27, respectively) and all-cause mortality (vs. bottom quartile: HDL-C-CV: 1.29, 1.27-1.31; HDL-C-SD: 1.24, 1.09-1.41; HDL-C-VIM: 1.25, 1.22-1.27, respectively). LDL-C variability was also associated with an increased risk of CVDs (for top vs. bottom quartile; LDL-C-SD: 1.09, 1.02-1.17; LDL-C-VIM: 1.16, 1.02-1.32, respectively) and all-cause mortality (for top vs. bottom quartile; LDL-C-CV: 1.19, 1.04-1.36; LDL-C-SD: 1.17, 1.09-1.26, respectively). The relationships of TG variability with the risk of CVDs and all-cause mortality were inconclusive across different metrics. The effects of SRR became stronger when analyses were restricted to studies that adjusted for lipid-lowering medication and unadjusted for mean lipid levels. These findings indicate that the measurement and surveillance of lipid variability might have important clinical implications for risk assessment of CVDs and all-cause mortality.
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http://dx.doi.org/10.3390/nu14122450DOI Listing
June 2022

Dielectric Properties Investigation of Metal-Insulator-Metal (MIM) Capacitors.

Molecules 2022 Jun 20;27(12). Epub 2022 Jun 20.

State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body, College of Mechanical and Vehicle Engineering, Hunan University, Changsha 410082, China.

This study presents the construction and dielectric properties investigation of atomic-layer-deposition AlO/TiO/HfO dielectric-film-based metal-insulator-metal (MIM) capacitors. The influence of the dielectric layer material and thickness on the performance of MIM capacitors are also systematically investigated. The morphology and surface roughness of dielectric films for different materials and thicknesses are analyzed via atomic force microscopy (AFM). Among them, the 25 nm AlO-based dielectric capacitor exhibits superior comprehensive electrical performance, including a high capacitance density of 7.89 fF·µm, desirable breakdown voltage and leakage current of about 12 V and 1.4 × 10 A·cm, and quadratic voltage coefficient of 303.6 ppm·V. Simultaneously, the fabricated capacitor indicates desirable stability in terms of frequency and bias voltage (at 1 MHz), with the corresponding slight capacitance density variation of about 0.52 fF·µm and 0.25 fF·µm. Furthermore, the mechanism of the variation in capacitance density and leakage current might be attributed to the Poole-Frenkel emission and charge-trapping effect of the high- materials. All these results indicate potential applications in integrated passive devices.
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http://dx.doi.org/10.3390/molecules27123951DOI Listing
June 2022

Analyses of n-back high-load working memory in early Parkinson's disease: An fMRI study.

J Clin Neurosci 2022 Jun 20;102:80-86. Epub 2022 Jun 20.

Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:

Background: Cognitive impairment is common in Parkinson's disease (PD). Working memory is a group of basic processes that is part of many cognitive operations (from complex decision-making to selective attention). To date, there is not sufficient research on working memory impairment in early PD patients, especially patients under high load.

Aim: The aim of this study was to observe the activation of brain regions in early PD patients during verbal high-load cognitive tasks and to explore the correlation between cognitive behavior indexes and gray matter areas of brain structure.

Methods: A total of 45 participants were included: 15 healthy controls and 30 PD patients without dementia. They underwent BOLD imaging during a digital N-back working memory task in a 3 T scanner, and their high-resolution T1-weighted three-dimensional brain anatomical images were collected. The SPM12 standard method was used to generate a comparison map with 2 plus 3-back greater than 0-back, and with age, sex, levodopa equivalent daily dose (LEDD) and education as covariables, and multiple regression analysis was conducted to analyze the correlation between MOCA, MES and brain gray matter volume.

Results: Compared with the control group, the frontoparietal region was significantly activated in patients with PD under the background of high working memory burden. In addition, there was a widespread area correlation between the brain structure and basic cognitive function.

Conclusions: The frontoparietal cortex is the core hub of working memory, and there may be a compensation mechanism in PD patients without dementia with a high-load of working memory.
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http://dx.doi.org/10.1016/j.jocn.2022.06.010DOI Listing
June 2022

Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2.

Toxics 2022 Jun 16;10(6). Epub 2022 Jun 16.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.

Exposure to environmental pollutants, including dioxin-like polychlorinated biphenyls (PCBs), play an important role in vascular inflammation and cardiometabolic diseases (CMDs) by inducing oxidative stress. Earlier, we demonstrated that oxidative stress-mediated lipid peroxidation derived 4-hydroxy-2-nonenal (4HNE) contributes to CMDs by decreasing the angiogenesis of coronary endothelial cells (CECs). By detoxifying 4HNE, aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, enhances CEC angiogenesis. Therefore, we hypothesize that ALDH2 activation attenuates a PCB 126-mediated 4HNE-induced decrease in CEC angiogenesis. To test our hypothesis, we treated cultured mouse CECs with 4.4 µM PCB 126 and performed spheroid and aortic ring sprouting assays, the ALDH2 activity assay, and Western blotting for the 4HNE adduct levels and real-time qPCR to determine the expression levels of and oxidative stress-related genes. PCB 126 increased the gene expression and 4HNE adduct levels, whereas it decreased the ALDH2 activity and angiogenesis significantly in MCECs. However, pretreatment with 2.5 µM disulfiram (DSF), an ALDH2 inhibitor, or 10 µM Alda 1, an ALDH2 activator, before the PCB 126 challenge exacerbated and rescued the PCB 126-mediated decrease in coronary angiogenesis by modulating the 4HNE adduct levels respectively. Finally, we conclude that ALDH2 can be a therapeutic target to alleviate environmental pollutant-induced CMDs.
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http://dx.doi.org/10.3390/toxics10060328DOI Listing
June 2022

Family Socioeconomic Position and Lung Cancer Risk: A Meta-Analysis and a Mendelian Randomization Study.

Front Public Health 2022 6;10:780538. Epub 2022 Jun 6.

Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Family socioeconomic position (SEP) in childhood is an important factor to predict some chronic diseases. However, the association between family SEP in childhood and the risk of lung cancer is not clear.

Methods: A systematic search was performed to explore their relationship. We selected education level, socioeconomic positions of parents and childhood housing conditions to represent an individual family SEP. Hazard ratios (HRs) of lung cancer specific-mortality were synthesized using a random effects model. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SEP to assess the possible causal relationship of SEP and risk of lung cancer.

Results: Through meta-analysis of 13 studies, we observed that to compared with the better SEP, the poorer SEP in the childhood was associated with the increased lung cancer risk in the adulthood (HR: 1.25, 95% CI: 1.10 to 1.43). In addition, the dose-response analysis revealed a positive correlation between the poorer SEP and increased lung cancer risk. Same conclusion was reached in MR [(education level) OR 0.50, 95% CI: 0.39 to 0.63; < 0.001].

Conclusion: This study indicates that poor family socioeconomic position in childhood is causally correlated with lung cancer risk in adulthood.

Systematic Review Registration: identifier: 159082.
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http://dx.doi.org/10.3389/fpubh.2022.780538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207765PMC
June 2022

Establishment and Optimization of Molecular Cytogenetic Techniques (45S rDNA-FISH, GISH, and Fiber-FISH) in Kiwifruit ( Lindl.).

Front Plant Sci 2022 6;13:906168. Epub 2022 Jun 6.

College of Horticulture and Landscape Architecture, Southwest University, Chongqing, China.

The kiwifruit () has long been regarded as "the king of fruits" for its nutritional importance. However, the molecular cytogenetics of kiwifruit has long been hampered because of the large number of basic chromosome ( = 29), the inherent small size and highly similar morphology of metaphase chromosomes. Fluorescence hybridization (FISH) is an indispensable molecular cytogenetic technique widely used in many plant species. Herein, the effects of post-hybridization washing temperature on FISH, blocking DNA concentration on genomic hybridization (GISH), extraction method on nuclei isolation and the incubation time on the DNA fiber quality in kiwifruit were evaluated. The post-hybridization washing in 2 × saline sodium citrate (SSC) solution for 3 × 5 min at 37C ensured high stringency and distinct specific FISH signals in kiwifruit somatic chromosomes. The use of 50 × blocking DNA provided an efficient and reliable means of discriminating between chromosomes derived from in the hybrids of var. (2 = 2 = 58) × (2 = 2 = 58), and inferring the participation of parental genitors. The chopping method established in the present study were found to be very suitable for preparation of leaf nuclei in kiwifruit. A high-quality linear DNA fiber was achieved by an incubation of 20 min. The physical size of 45S rDNA signals was approximately 0.35-0.40 μm revealed by the highly reproducible fiber-FISH procedures established and optimized in this study. The molecular cytogenetic techniques (45S rDNA-FISH, GISH, and high-resolution fiber-FISH) for kiwifruit was for the first time established and optimized in the present study, which is the foundation for the future genomic and evolutionary studies and provides chromosomal characterization for kiwifruit breeding programs.
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http://dx.doi.org/10.3389/fpls.2022.906168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208197PMC
June 2022

Liver cancer heterogeneity modeled by in situ genome editing of hepatocytes.

Sci Adv 2022 Jun 22;8(25):eabn5683. Epub 2022 Jun 22.

The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Mechanistic study and precision treatment of primary liver cancer (PLC) are hindered by marked heterogeneity, which is challenging to recapitulate in any given liver cancer mouse model. Here, we report the generation of 25 mouse models of PLC by in situ genome editing of hepatocytes recapitulating 25 single or combinations of human cancer driver genes. These mouse tumors represent major histopathological types of human PLCs and could be divided into three human-matched molecular subtypes based on transcriptomic and proteomic profiles. Phenotypical characterization identified subtype- or genotype-specific alterations in immune microenvironment, metabolic reprogramming, cell proliferation, and expression of drug targets. Furthermore, single-cell analysis and expression tracing revealed spatial and temporal dynamics in expression of (). Tumor-specific knockdown of by multiplexed genome editing reversed the Warburg effect and suppressed tumorigenesis in a genotype-specific manner. Our study provides mouse PLC models with defined genetic drivers and characterized phenotypical heterogeneity suitable for mechanistic investigation and preclinical testing.
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http://dx.doi.org/10.1126/sciadv.abn5683DOI Listing
June 2022

[Effects of CO concentration and soil water content on short-term water-use efficiency at whole-plant level].

Ying Yong Sheng Tai Xue Bao 2022 Jun;33(6):1505-1510

China Institute of Water Resources and Hydropower Research, Beijing 100048, China.

Uncovering the variations of short-term water-use efficiency (WUE) at whole-plant level in response to CO concentration () and soil water content (SWC) can improve the understanding of plant survival strategies under climate change. In this study, saplings were cultured in simulated climate chambers.There were totally 15 treatments, including of 400 (), 600 () and 800 () μmol·mol and SWC of 35%-45% field water holding capacity (FC), 50%-60%FC, 60%-70%FC, 70%-80%FC and 95%-100%FC. The WUE was measured by mini-lysimeters, weighting method, and static assimilation chamber. The results showed that both daytime (0.12-1.87 mol·h) and nighttime transpiration rates (0.01-0.16 mol·h) at whole-plant level reached the maximum at ×70%-80%FC, while the whole-plant daytime net photosynthetic rate (2.12-22.10 mmol·h) reached the maximum at ×70%-80%FC. In contrast, nighttime respiration rate (0.84-4.41 mmol·h) increased with increasing SWC, but decreased with increasing of , reaching the maximum at ×95%-100%FC. For WUE (5.37-24.35 mmol·mol), it reached the maximum at ×50%-60%FC, indicating that plants could use less water and fixed more carbon by adjusting adaptation strategies under high and drought conditions. In addition, leaf instantaneous water-use efficiency was a good predictor of WUE when the canopy structure was similar.
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http://dx.doi.org/10.13287/j.1001-9332.202206.002DOI Listing
June 2022

Mortality burden due to long-term exposure to ambient PM above the new WHO air quality guideline based on 296 cities in China.

Environ Int 2022 Jun 2;166:107331. Epub 2022 Jun 2.

School of Public Health and Management, Binzhou Medical University, Yantai, Shandong Province 264003, PR China; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. Electronic address:

Objective: Quantifying the spatial and socioeconomic variation of mortality burden attributable to particulate matters with aerodynamic diameter ≤ 2.5 µm (PM) has important implications for pollution control policy. This study aims to examine the regional and socioeconomic disparities in the mortality burden attributable to long-term exposure to ambient PM in China.

Methods: Using data of 296 cities across China from 2015 to 2019, we estimated all-cause mortality (people aged ≥ 16 years) attributable to the long-term exposure to ambient PM above the new WHO air quality guideline (5 µg/m). Attributed fraction (AF), attributed deaths (AD), attributed mortality rate (AMR) and total value of statistical life lost (VSL) by regional and socioeconomic levels were reported.

Results: Over the period of 2015-2019, 17.0% [95% confidence interval (CI): 7.4-25.2] of all-cause mortality were attributable to long-term exposure to ambient PM, corresponding to 1,425.2 thousand deaths (95% CI: 622.4-2,099.6), 103.5/10 (95% CI: 44.9-153.3) AMR, and 1006.9 billion USD (95% CI: 439.8-1483.4) total VSL per year. The AMR decreased from 120.5/10 (95% CI: 52.9-176.6) to 92.7/10 (95% CI:39.9-138.5) from 2015 to 2019. The highest mortality burden was observed in the north region (annual average AF = 24.2%, 95% CI: 10.8-35.1; annual average AMR = 137.0/10, 95% CI: 60.9-198.5). The highest AD and economic loss were observed in the east region (annual average AD = 390.0 thousand persons, 95% CI: 170.3-574.6; annual total VSL = 275.6 billion USD, 95% CI: 120.3-406.0). Highest AMR was in the cities with middle level of GDP per capita (PGDP)/urbanization. The majority of the top ten cities of AF, AMR and VSL were in high and middle PGDP/urbanization regions.

Conclusion: There were significant regional and socioeconomic disparities in PM attributed mortality burden among Chinese cities, suggesting differential mitigation policies are required for different regions in China.
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http://dx.doi.org/10.1016/j.envint.2022.107331DOI Listing
June 2022

Riclin-Capped Silver Nanoparticles as an Antibacterial and Anti-Inflammatory Wound Dressing.

Int J Nanomedicine 2022 13;17:2629-2641. Epub 2022 Jun 13.

Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, Jiangsu, 210094, People's Republic of China.

Purpose: In order to overcome the inflammatory response to bacterial infection during wound healing, we have fabricated an antibacterial and anti-inflammatory wound dressing based on polysaccharide riclin and silver nanoparticles (AgNPs).

Methods: The riclin-AgNPs nanocomposite was developed by borohydride method and was characterized by UV-Vis, TEM, XRD, Zeta potential, DLS. In vitro, we assessed the cumulative release, antibacterial activities and cytotoxicity. In vivo, we examined the wound healing in mice wound infection experiment and inflammatory mediators using histological observations and gene expression analysis.

Results: The riclin/AgNPs nanocomposite hydrogel exhibited nanosized orbicular particles with high purity and stability. In vitro, the riclin/AgNPs showed sustained release of AgNPs, effective suppression in pathogen growth and negligible toxicity toward mammalian fibroblasts and macrophage cells. In vivo, the riclin/AgNPs treatment leads to faster and smoother growth of fresh skin with suppressed expression of inflammatory mediators.

Conclusion: The reported Riclin-AgNPs nanocomposite hydrogel showed both antibacterial and anti-inflammatory functions, which induce significantly accelerated wound healing, indicating great potential as a novel attractive wound dressing material.
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http://dx.doi.org/10.2147/IJN.S366899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205441PMC
June 2022

Molecular Typing of Gastric Cancer Based on Invasion-Related Genes and Prognosis-Related Features.

Front Oncol 2022 3;12:848163. Epub 2022 Jun 3.

Department of Clinical Laboratory, The Affiliated Hospital of Guilin Medical University, Guilin, China.

Background: This study aimed to construct a prognostic stratification system for gastric cancer (GC) using tumour invasion-related genes to more accurately predict the clinical prognosis of GC.

Methodology: Tumour invasion-related genes were downloaded from CancerSEA, and their expression data in the TCGA-STAD dataset were used to cluster samples non-negative matrix factorisation (NMF). Differentially expressed genes (DEGs) between subtypes were identified using the limma package. KEGG pathway and GO functional enrichment analyses were conducted using the WebGestaltR package (v0.4.2). The immune scores of molecular subtypes were evaluated using the R package ESTIMATE, MCPcounter and the ssGSEA function of the GSVA package. Univariate, multivariate and lasso regression analyses of DEGs were performed using the coxph function of the survival package and the glmnet package to construct a RiskScore model. The robustness of the model was validated using internal and external datasets, and a nomogram was constructed based on the model.

Results: Based on 97 tumour invasion-related genes, 353 GC samples from TCGA were categorised into two subtypes, thereby indicating the presence of inter-subtype differences in prognosis. A total of 569 DEGs were identified between the two subtypes; of which, four genes were selected to construct the risk model. This four-gene signature was robust and exhibited stable predictive performance in different platform datasets (GSE26942 and GSE66229), indicating that the established model performed better than other existing models.

Conclusion: A prognostic stratification system based on a four-gene signature was developed with a desirable area under the curve in the training and independent validation sets. Therefore, the use of this system as a molecular diagnostic test is recommended to assess the prognostic risk of patients with GC.
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http://dx.doi.org/10.3389/fonc.2022.848163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203697PMC
June 2022

Modified technique for robot-assisted laparoscopic infantile ureteral reimplantation for obstructive megaureter.

J Pediatr Surg 2022 May 25. Epub 2022 May 25.

Department of Urology, the Seventh Medical Centre, Chinese PLA General Hospital, No.5 Nan Mencang, Dongcheng District, Beijing 100700, China.

Purpose: To describe a novel modification of technique to improve efficacy of robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) in infants.

Materials And Methods: Between April 2017 and July 2019, sixteen infants with primary obstructive megaureter (POM) (Age range: 4-12 months) underwent robot-assisted ureteral reimplantation were reviewed in this series. In addition to the conventional Lich-Gregoir technique, the detrusor tunnel has been extended to the mobilized anterior bladder wall to guarantee sufficient tunnel length/ureter diameter ratio and avoid ureteral angulation. All patients underwent repeated ultrasound, diuretic renal dynamic imaging and voiding cystourethrography (VCUG) perioperatively and the outcomes were documented.

Results: All operations were completed with robotic assisted approach without conversion. Bilateral and unilateral reimplantation were respectively performed in two and fourteen patients. The mean operative time was 115.0 ± 19.5 min and the mean blood loss was 10.0 ± 1.8 ml. There were no high-grade complications (III-IV on Clavien-Dindo classification) except for one patient. The distal ureteric diameter was reduced from pre operative 1.7 ± 0.5 to 0.6 ± 0.5 cm 6 months post operatively (p < 0.05). One child (6.3%) required the second reimplantation for stenosis. The overall operative success rate was 94.4% (17 of 18 ureters) with a mean follow-up of 15.9 ± 7.4 months with no flux detected.

Conclusion: Our preliminary experience suggests that our modified robot-assisted laparoscopic extravesical ureteral reimplantation is feasible in infants with good results.
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http://dx.doi.org/10.1016/j.jpedsurg.2022.05.015DOI Listing
May 2022

The Molecular Mechanism of Long Non-Coding RNA (LncRNA) Regulation of Notch Signaling in Glucose-Induced Apoptosis of Human Retinal Vascular Endothelial Cell.

J Biomed Nanotechnol 2022 Mar;18(3):891-897

Department of Ophthalmology, Chengdu First People's Hospital, Chengdu 610041, Sichuan, PR China.

Diabetes, a global health concern, affects the health of more than 500 million adults. The absence of Notch protein can cause an imbalance in the retinal vascular environment and cause retinal vascular disease. Long noncoding RNA (lncRNA) is known to be involved in the regulation of many signaling pathways. We hope to understand the specific mechanism of apoptosis in retinal vascular endothelial cells (RVECs) by exploring the regulatory effect of lncRNA on the Notch pathway. In this study, we found that RVECs treated with glucose showed increased levels of Notch transcript and protein expression. The lentiviral interference with Notch RNAi reversed this response. When Notch activity decreased, oxidative stress also decreased, accompanied by increased levels of Caspase-9 and Caspase-3 and an increased rate of apoptosis. Therefore, we believe that Notch is involved in the development of diabetic retinopathy and loss of expression promotes apoptosis of human RVECs. By inhibiting the Notch pathway, lncRNA promotes apoptosis of human RVECs in a high-glucose environment.
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http://dx.doi.org/10.1166/jbn.2022.3291DOI Listing
March 2022

Analysis of Clinical Features and Next-Generation Sequencing of 12 Tuberous Sclerosis Families in China.

Front Med (Lausanne) 2022 27;9:840709. Epub 2022 May 27.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with systemic organ involvement. So far, only a few TSC families in China have been reported. Therefore, more data on the clinical and genetic features of TSC families are required.

Materials And Methods: We retrospectively analyzed 12 TSC family probands and their family members. Next-generation sequencing (NGS) has been applied to confirm the type of TSC mutation along with a detailed physical examination.

Results: In this study, twenty-seven patients in 12 TSC families were reported, including 12 male and 15 female patients, aged 8-67 years. Skin lesions were detected among all patients with TSC, including 25 cases of facial angiofibromas, 18 cases of hypomelanotic macules, 15 cases of ungual fibromas, and 13 cases of shagreen patch. Other clinical features were also revealed: 14 cases of renal angiomyolipoma, 6 cases of subependymal nodules (SENs), and 3 cases of lymphangioleiomyomatosis. All twenty-seven patients with TSC were tested by NGS. Totally, mutations were reported in 19 cases (7 frameshift mutations, 10 nonsense mutations, and 2 missense mutations), mutations were reported in 4 cases (4 nonsense mutations), and 4 cases were genetically negative. The novel causal mutations (: c.208dup, c.1874C > G, c.1852del) identified in three families were first reported in TSC.

Conclusion: Our findings expand the mutation spectrum of patients with TSC in China. The clinical characteristics can vary among patients with TSC with the same pathogenic mutation. The genetic results and summary of clinical features of 12 TSC families contribute to a more accurate diagnosis and further genetic counseling.
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http://dx.doi.org/10.3389/fmed.2022.840709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197381PMC
May 2022

FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion.

Nat Commun 2022 Jun 17;13(1):3486. Epub 2022 Jun 17.

The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.

Mitochondria generate ATP and play regulatory roles in various cellular activities. Cancer cells often exhibit fragmented mitochondria. However, the underlying mechanism remains elusive. Here we report that a mitochondrial protein FUN14 domain containing 2 (FUNDC2) is transcriptionally upregulated in primary mouse liver tumors, and in approximately 40% of human hepatocellular carcinoma (HCC). Importantly, elevated FUNDC2 expression inversely correlates with patient survival, and its knockdown inhibits liver tumorigenesis in mice. Mechanistically, the amino-terminal region of FUNDC2 interacts with the GTPase domain of mitofusin 1 (MFN1), thus inhibits its activity in promoting fusion of outer mitochondrial membrane. As a result, loss of FUNDC2 leads to mitochondrial elongation, decreased mitochondrial respiration, and reprogrammed cellular metabolism. These results identified a mechanism of mitochondrial fragmentation in cancer through MFN1 inhibition by FUNDC2, and suggested FUNDC2 as a potential therapeutic target of HCC.
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http://dx.doi.org/10.1038/s41467-022-31187-6DOI Listing
June 2022

Study on the expression of c-Met in gastric cancer and its correlation with preoperative serum tumor markers and prognosis.

World J Surg Oncol 2022 Jun 16;20(1):204. Epub 2022 Jun 16.

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.

Background: Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with preoperative serum tumor markers and prognosis, in order to provide a more theoretical basis for targeting c-Met in the treatment of GC.

Methods: Ninety-seven patients who underwent curative gastrectomy in our hospital from December 2013 to September 2015 were included in this study. The tissue microarray was constructed by paraffin-embedded tumor tissue of enrolled patients, including 97 GC points and 83 paracancerous points. Then, it was used for c-Met immunohistochemical staining, followed by an immunological H-score. The clinical baseline data and 5-year survival of patients with low and high c-Met expression were compared. Besides, the correlation between the expression of c-Met in tumor tissues and preoperative serum tumor markers was investigated. Finally, multivariate Cox regression analysis was used to explore the survival risk factors of patients.

Results: c-Met has a high expression rate in GC tissues 64.95% (63/97). The expression of c-Met was significantly different in different clinicopathological stages (p < 0.05); the high expression group also had a higher M stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (p = 0.004), indicating a positive correlation. Furthermore, high c-Met expression correlated with poor overall survival (OS) for 5 years (p = 0.005). It was also found that the high expression of c-Met in stage I-II patients was correlative with poor OS for 5 years (p = 0.026), while stage III-IV patients had no statistical significance (p > 0.05). Multivariate Cox regression analysis showed that c-Met might be an independent risk factor for survival 5 years after surgery.

Conclusion: This study found that the high expression of c-Met in GC tissues was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after curative gastrectomy. The expression of c-Met in GC tissues was also positively correlated with preoperative serum CA125.
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http://dx.doi.org/10.1186/s12957-022-02659-2DOI Listing
June 2022

YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer.

ACS Chem Biol 2022 Jun 15. Epub 2022 Jun 15.

Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Oxaliplatin, as a first-line drug, frequently causes chemo-resistance in colorectal cancer (CRC). The role of N6-methyladenosine (m6A) modification in multiple biological functions has been well studied. However, the molecular mechanisms underlying m6A methylation in modulating anti-cancer drug resistance in CRC remain obscure. In the present study, we found that YTH m6A RNA-binding protein 3 (YTHDF3) was highly expressed in oxaliplatin-resistant (OXAR) CRC tissues and cells. Moreover, we observed that YTHDF3 could recognize the 5' untranslated region of significantly m6A-methylated RNAs, which were associated with tumor resistance and recruit eukaryotic translation initiation factor 3 subunit A (eIF3A) to facilitate the translation of these target genes. Furthermore, we determined that eukaryotic translation initiation factor 2 alpha kinase 2 (eIF2AK2) bridged YTHDF3 and eIF3A, enhancing the stability of the YTHDF3/eIF3A complex in OXAR CRC cells. Taken together, our data identified YTHDF3 as a novel hallmark and revealed the molecular mechanism of YTHDF3 on gene translation coordination with eIF2AK2 in OXAR CRC cells.
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http://dx.doi.org/10.1021/acschembio.2c00131DOI Listing
June 2022

The cell cycle gene centromere protein K () contributes to the malignant progression and prognosis of prostate cancer.

Transl Cancer Res 2022 May;11(5):1099-1111

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Background: The cell cycle gene centromere protein K () is upregulated in various cancers; however, the clinical value and mechanism of in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) remain unclear.

Methods: The expression of in PCa was analyzed in both patients with PCa and cell lines using immunohistochemistry (IHC), real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and bioinformatics analyses. Knockdown of in PCa cells was achieved by transfecting siRNAs and assessed using qRT-PCR and Western blotting. MTT and colony formation assays were used to assess the growth of PCa cells. The cell cycle was analyzed using propidium iodide (PI) staining and flow cytometry. To study the possible biological function of , pathway enrichment analysis was performed by dividing these groups into a high expression group and a low expression group based on the median expression level. Finally, the correlation between expression in PCa and clinical parameters was evaluated.

Results: Our study revealed that was expressed at high levels in CRPC tissues and cell lines compared to primary PCa. The downregulation of significantly inhibited cell viability and reduced the number of colonies formed by LNCaP-AI and DU145 cells (two CRPC cell lines). Gene enrichment and flow cytometry analyses showed that high expression was linked to mitotic spindles and the cell cycle and may be involved in mitosis in the cell cycle of cancer cells to modulate cell proliferation and promote the development of CRPC. Moreover, patients exhibiting higher expression of the mRNA experienced shorter disease-free survival (DFS) and overall survival (OS) than the lower expression group.

Conclusions: This study provides novel molecular insights into the role of in castration-resistant PCa cells and reveals that an increase in expression may indicate shorter DFS and a poor prognosis for patients with PCa. Targeting may be a novel strategy for the treatment of PCa.
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http://dx.doi.org/10.21037/tcr-21-2164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189231PMC
May 2022

Papillary renal neoplasm with reverse polarity: A case report.

Asian J Surg 2022 Jun 11. Epub 2022 Jun 11.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.166DOI Listing
June 2022

Correction: Dynamic trajectory of platelet counts after the first cycle of induction chemotherapy in AML patients.

BMC Cancer 2022 Jun 13;22(1):647. Epub 2022 Jun 13.

Center for Big Data Research in Health and Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.

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http://dx.doi.org/10.1186/s12885-022-09715-wDOI Listing
June 2022

Blood donation improves skin aging through the reduction of iron deposits and the increase of TGF-β1 in elderly skin.

Mech Ageing Dev 2022 Jun 10;205:111687. Epub 2022 Jun 10.

Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China. Electronic address:

Skin aging is characterized by a wide range of physiological and structural changes, including wrinkling, dyschromia, and roughness, as well as the reduction of dermal thickness and collagen content. Here, we showed that blood donation increased dermal thickness and collagen content and decreased the number of senescent cells in old mice. Transcriptomic and metabolomic studies revealed blood donation significantly altered aging-related pathways in the skin of old mice. Molecular genes analysis indicated blood donation decreased the expression of genes associated with inflammation such as Fols1, Cox-2, and IL-1β, and increased the expression of collagen-associated genes including TGF-β1, TGF-β2, and Col3a1. The improvement of skin aging by blood donation was associated with the reduction of iron deposits and the increase of TGF-β1 in elderly skin. Our results suggested that appropriate blood donation could promote collagen re-synthesis and improve skin aging.
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http://dx.doi.org/10.1016/j.mad.2022.111687DOI Listing
June 2022

Genetic and transcriptomic dissection of an artificially induced paired spikelets mutant of wheat (Triticum aestivum L.).

Theor Appl Genet 2022 Jun 13. Epub 2022 Jun 13.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, Sichuan, People's Republic of China.

Key Message: Morphological, genetic and transcriptomic characterizations of an EMS-induced wheat paired spikelets (PS) mutant were performed. A novel qualitative locus WPS1 on chromosome 1D was identified. Grain yield of wheat is significantly associated with inflorescence or spike architecture. However, few genes related to wheat spike development have been identified and their underlying mechanisms are largely unknown. In this study, we characterized an ethyl methanesulfonate (EMS)-induced wheat mutant, wheat paired spikelets 1 (wps1). Unlike a single spikelet that usually develops at each node of rachis, a secondary spikelet appeared below the primary spikelet at most of the rachis nodes of wps1. The microscope observation showed that the secondary spikelet initiated later than the primary spikelet. Genetic analysis suggested that the PS of wps1 is controlled by a single dominant nuclear gene, designated WHEAT PAIRED SPIKELETS 1 (WPS1). Further RNA-seq based bulked segregant analysis and molecular marker mapping localized WPS1 in an interval of 208.18-220.92 Mb on the chromosome arm 1DL, which is different to known genes related to spike development in wheat. By using wheat omics data, TraesCS1D02G155200 encoding a HD-ZIP III transcription factor was considered as a strong candidate gene for WPS1. Transcriptomic analysis indicated that PS formation in wps1 is associated with auxin-related pathways and may be regulated by networks involving TB1, Ppd1, FT1, VRN1, etc. This study laid the solid foundation for further validation of the causal gene of WPS1 and explored its regulatory mechanism in PS formation and inflorescence development, which may benefit to kernel yield improvement of wheat based on optimization or design of spike architecture in the future.
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http://dx.doi.org/10.1007/s00122-022-04137-5DOI Listing
June 2022

A New Way Out of the Predicament of Anaplastic Thyroid Carcinoma From Existing Data Analysis.

Front Endocrinol (Lausanne) 2022 26;13:887906. Epub 2022 May 26.

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

Background: Anaplastic thyroid carcinoma (ATC) is an endocrine tumor with a low incidence but a very poor prognosis. The vast majority of patients have a survival time of only three to six months, but a few survive for two years or more. In recent years, there have been major breakthroughs in targeted and immunotherapy in the field of oncology therapy. Although the preliminary study for ATC showed a promising prospect, more clinical trials are needed. It is the best approach to explore the measures that can improve survival time of ATC from the available clinical data, especially those with long survival.

Methods: We report on an 82-year-old ATC patient who survived for 3 years and systematically review the clinical characteristics of 45 ATC patients with complete data from the two largest centers in northwest China. In particular, factors related to long-term survival were analyzed and summarized.

Results: Three years prior, an 82-year-old woman was diagnosed with ATC by core needle biopsy following a physical examination. The thyroid tumor was resected within one month, and then the patient was treated with radiotherapy. The patient was still healthy after three years of follow-up. Analysis of prognostic factors for the 45 reviewed patients showed that those undergoing radical surgery (median overall survival (OS) = 472 days, = 0.0261) and radiotherapy (median OS = 220 days, = 0.0136) had better outcomes. In addition, patients younger than 65 years (median OS = 164.5 days, = 0.0176) and with a lower tumor stage (IV A, median OS = 633.5 days, = 0.0191) also had a better outcome.

Conclusion: ATC is a highly malignant tumor, but timely early diagnosis and standardized treatment with radical surgery and radiotherapy as the core can achieve good results. Some patients can achieve long-term survival.
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http://dx.doi.org/10.3389/fendo.2022.887906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178175PMC
June 2022

Correlative Assembly of Subsynaptic Nanoscale Organizations During Development.

Front Synaptic Neurosci 2022 24;14:748184. Epub 2022 May 24.

Chinese Academy of Sciences (CAS) Key Laboratory of Brain Function and Disease, Ministry of Education Key Laboratory for Membrane-less Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Nanoscale organization of presynaptic proteins determines the sites of transmitter release, and its alignment with assemblies of postsynaptic receptors through nanocolumns is suggested to optimize the efficiency of synaptic transmission. However, it remains unknown how these nano-organizations are formed during development. In this study, we used super-resolution stochastic optical reconstruction microscopy (STORM) imaging technique to systematically analyze the evolvement of subsynaptic organization of three key synaptic proteins, namely, RIM1/2, GluA1, and PSD-95, during synapse maturation in cultured hippocampal neurons. We found that volumes of synaptic clusters and their subsynaptic heterogeneity increase as synapses get matured. Synapse sizes of presynaptic and postsynaptic compartments correlated well at all stages, while only more mature synapses demonstrated a significant correlation between presynaptic and postsynaptic nano-organizations. After a long incubation with an inhibitor of action potentials or AMPA receptors, both presynaptic and postsynaptic compartments showed increased synaptic cluster volume and subsynaptic heterogeneity; however, the trans-synaptic alignment was intact. Together, our results characterize the evolvement of subsynaptic protein architectures during development and demonstrate that the nanocolumn is organized more likely by an intrinsic mechanism and independent of synaptic activities.
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http://dx.doi.org/10.3389/fnsyn.2022.748184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171000PMC
May 2022

Research on 3D-Print Design Method of Spatial Node Topology Optimization Based on Improved Material Interpolation.

Materials (Basel) 2022 May 29;15(11). Epub 2022 May 29.

Zhejiang Southest Space Frame Co., Ltd., Hangzhou 310058, China.

Designing a high-strength node is significant for space structures. Topological optimization can optimally allocate the material distribution of components to meet performance requirements. Although the material distribution after topology optimization is optimum, the structure becomes complicated to manufacture. By using additive manufacturing technology, this problem can be well solved. At present, both topology optimization technology and additive manufacturing technology are quite mature, but their application in the design of spatial nodes is very recent and less researched. This paper involves the study and improvement of the node optimization design-manufacturing integrated method. This study used the BESO optimization algorithm as the research algorithm. Through a reasonable improvement of the material interpolation method, the algorithm's dependence on the experience of selecting the material penalty index P was reduced. On this basis, the secondary development was carried out, and a multisoftware integration was carried out for optimization and manufacturing. The spatial node was taken as the research object, and the calculation results of the commercial finite element software were compared. The comparison showed that the algorithm used in this paper was better. Not only was it not trapped in a local optimum, but the maximum stress was also lower. In addition, this paper proposed a practical finite element geometric model extraction method and smoothing of the optimized nodes, completing the experiment of the additive manufacturing forming of the nodes. It provides ideas for processing jagged edges brought by the BESO algorithm. This paper verified the feasibility of the multisoftware integration method of optimized manufacturing.
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http://dx.doi.org/10.3390/ma15113874DOI Listing
May 2022

Automatic Cobb angle measurement method based on vertebra segmentation by deep learning.

Med Biol Eng Comput 2022 Jun 9. Epub 2022 Jun 9.

School of Information, Yunnan University, East outer ring south road, Kunming, 650504, China.

The accuracy of the Cobb measurement is essential for the diagnosis and treatment of scoliosis. Manual measurement is however influenced by the observer variability hence affecting progression evaluation. In this paper, we propose a fully automatic Cobb measurement method to address the accuracy issue of manual measurement. We improve the U-shaped network based on the multi-scale feature fusion to segment each vertebra. To enable multi-scale feature extraction, the convolution kernel of the U-shaped network is substituted by the Inception Block. To solve the problem of gradient disappearance caused by the widening of the network structure from the Inception Block, we propose using Res Block. CBAM (Convolutional Block Attention Module) can help the network judges the importance of the feature map to modify learning weight. Also, to further enhance the accuracy of feature extraction, we add the CBAM to the U-shaped network bottleneck. Finally, based on the segmented vertebrae, the efficient automatic Cobb angle measurement method is proposed to estimate the Cobb angle. In the experiments, 75 spinal X-ray images are tested. We compare the proposed U-Shaped network with the state-of-the-art methods including DeepLabV3 + , FCN8S, SegNet, U-Net, U-Net +  + , BASNet, and UNet for vertebra segmentation. Our results show that compared to these methods, the Dice coefficient is improved by 32.03%, 33.58%, 12.42%, 5.65%, 4.55%, 4.42%, and 3.27%, respectively. The CMAE of the calculated Cobb measurement is 2.45°, which is lower than the average error of 5-7° of manual measurement. The experimental results indicate that the improved U-shaped network improves the accuracy of vertebra segmentation. The proposed efficient automatic Cobb measurement method can be used in clinics to reduce observer variability.
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http://dx.doi.org/10.1007/s11517-022-02563-7DOI Listing
June 2022

Comparison of the Biological Characteristics and Molecular Mechanisms of Fludioxonil-Resistant Isolates of from Tomato in Liaoning Province of China.

Plant Dis 2022 Jun 9:PDIS07211446RE. Epub 2022 Jun 9.

Institute of Plant Protection, Liaoning Academy of Agricultural Sciences, Shenyang 110161, People's Republic of China.

is a common filamentous phytopathogen that causes serious pre- and postharvest losses worldwide. The phenylpyrrole fungicide fludioxonil has been reported to have high activity against and has been applied to control gray mold in tomato. A total of 206 isolates were collected from tomato greenhouses in Liaoning Province, China, in 2016 and 2017, and sensitivity to fludioxonil was demonstrated by discriminatory concentrations. One highly fludioxonil-resistant isolate, 5 medium-fludioxonil-resistance isolates, and 23 low-fludioxonil-resistance isolates were detected in the field. The fludioxonil-resistant isolates were less fit than the sensitive isolates and presented reduced sporulation, pathogenicity, and mycelial growth and hypersensitivity to osmotic stress, even though sclerotium production had no connection with resistance. Positive cross-resistance was observed between fludioxonil and the dicarboximide fungicides procymidone and iprodione but not between fludioxonil and the fungicides boscalid, fluopyram, fluazinam, and pyrimethanil. Sequence alignment of the gene indicated that the observed sensitivity was identical to that of B05.10 and the low-resistance mutant had two types of mutations, F127S+I365N and A1259T. The medium-resistance mutants had only one type of mutation linked with the 3-aa mutant Q369P+N373S+A1259T, and the highly resistant mutant had a 3-aa mutation with I365S+N373S+A1259T. Molecular docking illustrated that all the resistant isolates showed less affinity than the sensitive isolates with fludioxonil.
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http://dx.doi.org/10.1094/PDIS-07-21-1446-REDOI Listing
June 2022

The application of omics techniques to evaluate the effects of Tanshinone IIA on dextran sodium sulfate induced ulcerative colitis.

Mol Omics 2022 Jun 7. Epub 2022 Jun 7.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Ulcerative colitis (UC) is the most frequent disease classified under the umbrella term inflammatory bowel disease (IBD) with potentially serious symptoms and devastating consequences for the affected patients. In clinical research, , which includes the active ingredient of Tanshinone IIA, has been proven to have an anti-inflammatory effect. However, Tan IIA anti-inflammatory effect and mechanism are not clear. In this study, the pharmacodynamic index was used to evaluate the effects of Tan IIA on UC mice, such as general conditions, disease activity index (DAI), pathological morphology of the colon and pharmacodynamic indices were taken into account. The UPLC-Q-Exactive Orbitrap/MS technology was further utilized to conduct a metabolomic analysis of mice's colon tissue to explore the intervention approaches. The results demonstrated that Tan IIA could significantly improve the general condition of UC mice, decrease DAI score and histopathological score, reduce the concentrations of TNF-α, IL-1β, IL-6 and increase IL-10 in the serum. Twenty endogenous components, such as taurine, L-glutamine were recognized as underlying biomarkers of the curative effect of Tan IIA. According to the system network analysis of the corresponding ways, the effect of Tan IIA on UC in mice is mainly through the regulation of taurine and hypotaurine metabolism. Tan IIA has been shown to possess definite pharmacological activities on the pharmacodynamic indexes and pathological observations on UC mice by partially regulating the destabilized network. Moreover, the findings acquired from the present study may provide a better understanding of the mechanisms of UC disease and potential therapies.
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http://dx.doi.org/10.1039/d2mo00074aDOI Listing
June 2022
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