Publications by authors named "Shuai Yang"

310 Publications

Synthesis of 9-Fluorenylidenes via Pd-Catalyzed C-H Vinylation with Vinyl Bromides.

Org Lett 2021 Sep 24. Epub 2021 Sep 24.

School of Chemical Science and Engineering, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University 1239 Siping Road, Shanghai 200092, China.

A facile and efficient approach for the synthesis of 9-fluorenylidenes has been developed via the palladium-catalyzed cross-coupling of 2-iodobiphenyls and vinyl bromides. The reaction involves the C-H activation of 2-iodobiphenyls and dual C-C bond formations. A range of 9-fluorenylidene derivatives, including diphenyldibenzofulvenes, can be synthesized with the reaction.
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http://dx.doi.org/10.1021/acs.orglett.1c02722DOI Listing
September 2021

Glycine-Serine-Threonine Metabolic Axis Delays Intervertebral Disc Degeneration through Antioxidant Effects: An Imaging and Metabonomics Study.

Oxid Med Cell Longev 2021 25;2021:5579736. Epub 2021 Aug 25.

Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, China 266003.

Although intervertebral disc degeneration (IDD) can be described as different stages of change through biological methods, this long and complex process cannot be defined in stages by single or simple combination of biological techniques. Under the background of the development of nuclear magnetic resonance (NMR) technology and the emerging metabonomics, we based on animal models and expanded to the study of clinical human degeneration models. The characteristics of different stages of IDD were analyzed by omics. Omics imaging combined with histology, cytology, and proteomics was used for screening of the intervertebral disc (IVD) of research subjects. Furthermore, mass spectrometry nontargeted metabolomics was used to explore profile of metabolites at different stages of the IDD process, to determine differential metabolic pathways and metabolites. NMR spectroscopy was used to qualitatively and quantitatively identify markers of degeneration. NMR was combined with mass spectrometry metabolomics to explore metabolic pathways. Metabolic pathways were determined through protein molecular biology and histocytology of the different groups. Distinguishing advantages of magnetic resonance spectroscopy (MRS) for analysis of metabolites and effective reflection of structural integrity and water molecule metabolism through diffusion tensor imaging (DTI) were further used to verify the macrometabolism profile during degeneration. A corresponding model of metabolomics and omics imaging was established. The findings of this study show that a series of metabolic pathways associated with the glycine-serine-threonine (Gly-Ser-Thr) metabolic axis affects carbohydrate patterns and energy utilization efficiency and ultimately delays disc degeneration through antioxidant effects.
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http://dx.doi.org/10.1155/2021/5579736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416401PMC
August 2021

Bi/Se-Based Nanotherapeutics Sensitize CT Image-Guided Stereotactic Body Radiotherapy through Reprogramming the Microenvironment of Hepatocellular Carcinoma.

ACS Appl Mater Interfaces 2021 Sep 2;13(36):42473-42485. Epub 2021 Sep 2.

Center for Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province 519000, P. R. China.

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4 and CD8 T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.
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http://dx.doi.org/10.1021/acsami.1c11763DOI Listing
September 2021

The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice.

Liver Int 2021 Aug 30. Epub 2021 Aug 30.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Background & Aims: Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota.

Methods: Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion.

Results: We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival.

Conclusion: We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).
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http://dx.doi.org/10.1111/liv.15047DOI Listing
August 2021

A Detailed Spatial Expression Analysis of Wing Phenotypes Reveals Novel Patterns of Odorant Binding Proteins in the Soybean Aphid, .

Front Physiol 2021 28;12:702973. Epub 2021 Jul 28.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

The wide range of insect niches has led to a rapid expansion of chemosensory gene families as well as their relatively independent evolution and a high variation. Previous studies have revealed some functions for odorant-binding proteins (OBPs) in processes beyond olfaction, such as gustation and reproduction. In this study, a comparative transcriptomic analysis strategy was applied for the soybean aphid, , focusing on various functional tissues and organs of winged aphids, including the antenna, head, leg, wing, thorax, cauda, and cornicle. Detailed spatial OBP expression patterns in winged and wingless parthenogenetic aphids were detected by RT-qPCR. Twelve OBPs were identified, and three new s in are first reported. All s showed comparatively higher expression in sensory organs and tissues, such as the antenna, head, or leg. Additionally, we found some novel expression patterns for aphid OBPs (Beckendorf et al., 2008). Five OBPs exhibited high-expression levels in the cauda and four in the cornicle (Biasio et al., 2015). Three genes () were highly expressed in the wing (Calvello et al., 2003). Two () were significantly more highly expressed in the wingless thorax than in the winged thorax with the wings removed, and these transcripts were significantly enriched in the removed wings. More details regarding OBP spatial expression were revealed under our strategy. These findings supported the existence of carrier transport functions other than for foreign chemicals and therefore broader ligand ranges of aphid OBPs. It is important for understanding how insect OBPs function in chemical perception as well as their other potential physiological functions.
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http://dx.doi.org/10.3389/fphys.2021.702973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376974PMC
July 2021

Disrupted Topological Organization of Functional Networks in Asymptomatic Carotid Plaque Without Significant Carotid Stenosis: A Resting-State fMRI Study.

Front Hum Neurosci 2021 5;15:685763. Epub 2021 Aug 5.

Hunan Clinical Research Center for Cerebrovascular Disease, Xiangya Hospital, Central South University, Changsha, China.

Previous studies have found that there are significant changes in functional network properties for patients with moderate to severe carotid artery stenosis. Our study aimed to explore the topology properties of brain functional network in asymptomatic patients with carotid plaque without significant stenosis. A total of 61 asymptomatic patients with carotid plaque (mean age 61.79 ± 7.35 years) and 25 healthy control subjects (HC; 58.12 ± 6.79 years) were recruited. General data collection, carotid ultrasound examination and resting state functional magnetic resonance imaging were performed on all subjects. Graph-theory was applied to examine the differences in the brain functional network topological properties between two groups. In the plaque group, E( = 0.03), γ ( = 0.01), and σ ( = 0.01) were significantly higher than in the HC group. The degree centrality of left middle frontal gyrus and the nodal efficiency of left middle frontal gyrus and right inferior parietal angular gyrus were significantly higher in the plaque group than in HC. The degree centrality and betweenness centrality of right middle temporal gyrus, as well as the nodal efficiency of right middle temporal gyrus, were significantly lower in the plaque group than in HC. The brain functional networks of patients with carotid plaques differ from those of healthy controls. Asymptomatic patients with carotid plaques exhibit increased local and global connectivity, which may reflect subtle reorganizations in response to early brain damage.
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http://dx.doi.org/10.3389/fnhum.2021.685763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375554PMC
August 2021

Relationships Between a Range of Inflammatory Biomarkers and Subjective Sleep Quality in Chronic Insomnia Patients: A Clinical Study.

Nat Sci Sleep 2021 12;13:1419-1428. Epub 2021 Aug 12.

Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), People's Republic of China.

Purpose: To examine whether associations exist between chronic insomnia disorder (CID) and overlooked inflammatory factors (Serum amyloid protein A [SAA]), tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], and regulated on activation and normal T cell expressed and presumably secreted [RANTES]).

Patients And Methods: A total of 65 CID patients and 39 sex- and age-matched good sleeper (GS) controls participated in this study. They completed a baseline survey to collect data on demographics, and were elevated sleep and mood by Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), 17-item Hamilton Depression Rating Scale (HAMD-17) and 14-item Hamilton Anxiety Rating Scale (HAMA-14), respectively. The blood samples were collected and tested the serum levels of SAA, TNF-α, GM-CSF and RANTES.

Results: The CID group had higher serum levels of SAA, TNF-α, and GM-CSF and a lower level of RANTES than the GS group. In the Spearman correlation analysis, SAA and GM-CSF positively correlated with the PSQI and AIS scores. After controlling for sex, HAMD-17 score, and HAMA-14 score, the partial correlation analysis showed that GM-CSF was positively correlated with PSQI score. Further stepwise linear regression analyses showed that GM-CSF was positively associated with the PSQI and AIS scores, while RANTES was negatively associated with them, and SAA was positively associated with just the AIS score.

Conclusion: The serum levels of inflammatory mediators (SAA, TNF-α, and GM-CSF) were significantly elevated and the level of RANTES was significantly decreased in CID patients and, to some extent, the changes are related to the severity of insomnia. These findings may help us to improve interventions to prevent the biological consequences of CID by inhibiting inflammation, thereby promoting health.
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http://dx.doi.org/10.2147/NSS.S310698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369225PMC
August 2021

Differentiation between Chaenomelis Fructus and its common adulterant, Guangpi Mugua.

J AOAC Int 2021 Aug 19. Epub 2021 Aug 19.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Material Medical Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China.

Background: The dried fruit of Chaenomeles speciosa, known as Chaenomelis Fructus or Zhoupi Mugua is a type of Traditional Chinese Medicine (TCM) that is widely used to treat many diseases. In addition, Guangpi Mugua, the dried fruit of the Chaenomeles sinensis, is its most commonly known adulterant.

Objective: To establish a robust approach for the quality control and identification of Chaenomelis Fructus.

Methods: Thin-layer Chromatography (TLC) was optimized and used to discriminate Chaenomelis Fructus from Guangpi Mugua. In addition, High-performance Liquid Chromatography (HPLC) method combined with fingerprint analysis and Partial Least-squares Discrimination Analysis (PLS-DA) was employed to study the chemical differences between Chaenomelis Fructus and Guangpi Mugua. Moreover, the Single Standard to Determine Multi-components (SSDMC) method with credible precision, repeatability, stability and durability was developed for quantitative analysis of the abundant markers.

Results: The developed TLC and HPLC methods were effective in the authentication of Chaenomelis Fructus. Moreover, oleanolic acid, ursolic acid, pomolic acid, corosolic acid, 3-O-acetylpomolic acid and one unknown compound, were identified to be critical markers for the discrimination of Chaenomelis Fructus from Guangpi Mugua.

Conclusions: Adulteration has always been a challenge in the development of TCM. This study therefore presents useful insights that may help solve the problem of adulteration during the preparation of Chaenomelis Fructus.

Highlights: The present study provided a systematic method for the quality control of Chaenomelis Fructus. This was therefore the first step towards solving the problem of adulteration in an attempt to improve the clinical safety and effectiveness of Chaenomelis Fructus.
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http://dx.doi.org/10.1093/jaoacint/qsab107DOI Listing
August 2021

Discovery of a CPS1-deficient HCC subtype with therapeutic potential via integrative genomic and experimental analysis.

Hepatology 2021 Aug 3. Epub 2021 Aug 3.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.

Background And Aims: Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack of in-depth study. Here, through analysis of big databases and clinical samples, we identified Carbamoyl phosphate synthetase I(CPS1)-deficient hepatocellular carcinoma(HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as target for HCC prevention.

Approach And Results: Pan-cancer study involving differentially expressed metabolic genes of 7,764 tumor samples in 16 cancer types provided by The Cancer Genome Atlas(TCGA) demonstrated that urea cycle(UC) was liver-specific and HCC-downregulated. A large-scale gene expression data analysis including a total of 2,596 HCC cases in 7 HCCDB datasets combined with a total of 17,444 hepatectomy cohort data identified a specific CPS1-deficent HCC subtype with poor clinical prognosis. In vitro and in vivo validation confirmed crucial role of CPS1 in HCC. LC-MS assay and Seahorse analysis revealed that UC dysregulation(UCD) led to the deceleration of the tricarboxylic acid(TCA) cycle, while excess ammonia caused by CPS1 deficiency activated fatty acid β-oxidation(FAO) through p-AMPK. Mechanistically, FAO provided sufficient ATP for cell proliferation and enhanced chemoresistance of HCC cells by activating FOXM1. Subcutaneous xenograft tumor models and patient-derived organoids(PDOs) were employed to identify that blocking FAO by Eto may provide therapeutic benefit to HCC patients with CPS1-deficiency.

Conclusions: In conclusion, our results prove a direct link between UCD and cancer stemness in HCC, define a CPS1-deficient HCC subtype through big-data mining, and provide insights for novel therapeutic for this type of HCC through targeting FAO.
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http://dx.doi.org/10.1002/hep.32088DOI Listing
August 2021

The Role of Four-Dimensional Automatic Right Ventricular Quantification Technology to Determine RV Function and Hemodynamics in Patients With Pulmonary Hypertension Compared With Right Heart Catheterization.

Front Cardiovasc Med 2021 14;8:628610. Epub 2021 Jul 14.

State Key Laboratory of Cardiovascular Disease, Department of Echocardiography, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Four-dimensional automatic right ventricular quantification technology (4D auto-RVQ) is a new method that can simultaneously measure right ventricular (RV) structure and strain. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. We assessed the 4D auto-RVQ to measure right heart structure, function, and hemodynamics in patients with pulmonary hypertension (PHTN) correlated with right heart catheterization (RHC). We enrolled a prospective cohort of 103 patients with PHTN and 25 healthy controls between September 2017 and December 2018. All patients with PHTN underwent echocardiography and RHC. Patients were included if they underwent two-dimensional (2D) and 4D auto-RVQ echocardiographic sequences on the same day as RHC. We analyzed RV functional indices using 2D and 4D auto-RVQ analyses. We divided patients with PHTN into three groups according to echocardiographic image quality as follows: high ( = 24), average ( = 48), and poor ( = 4). Hemodynamic parameters were measured using RHC, including mean right atrial pressure, mean pulmonary arterial pressure, RV cardiac index (RV-CI), and pulmonary vascular resistance. There were significant differences in most 2D and 4D auto-RVQ parameters between patients with PHTN and healthy controls. Interobserver variability showed significant agreement with 4D auto-RVQ for most measurements except for 4D end-diastolic volume. Indices measured by auto 4D-RVQ in the high-quality image group had a good correlation with RHC but not in the average- and poor-quality image group. Mid-RV diameter showed the best predictive power for the right RV-CI [area under the curve (AUC) 0.935; 95% confidence interval (CI), 0.714-0.997; < 0.001]. RV end-systolic volume >121.50 mL had a 71.43% sensitivity and a 100% specificity to predict right RV-CI (AUC, 0.890; 95% CI, 0.654-0.986; < 0.001). 4D auto-RVQ may be used to estimate RV function and some hemodynamic changes compared with RHC in PHTN patients with high image quality. Furthermore, a large sample of the study is needed to evaluate RV function by 4D auto-RVQ in PHTN patients with average image quality.
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http://dx.doi.org/10.3389/fcvm.2021.628610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316584PMC
July 2021

Wearable Electronics Based on the Gel Thermogalvanic Electrolyte for Self-Powered Human Health Monitoring.

ACS Appl Mater Interfaces 2021 Aug 30;13(31):37316-37322. Epub 2021 Jul 30.

Micro Nano System Research Center, College of Information and Computer & Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan 030024, China.

There is always a temperature difference of more than 10 degrees between the human body, as a sustainable heat source, and the ambient temperature. Converting body heat into electricity that in turn is used to drive personal medical electronics is of significance in smart wearable medicine. To avoid the frangibility and complex preparation of traditional thermoelectric materials, we fabricated a gel electrolyte-based thermogalvanic generator with Fe/Fe as a redox pair, which presents not only moderate thermoelectric performance but also excellent flexibility. With a micropore-widespread polyvinylidene fluoride diaphragm implanted in the gel, a thermal barrier was created between the two halves, effectively improving the Seebeck coefficient by reducing its thermal conductivity. Considering the superior temperature response of the gel, a self-powered body temperature monitoring system was established by conformally affixing it to the forehead. Meanwhile, the gel patch with a high specific heat capacity can effectively cool down fever patients. This work may offer a new train of thought for exploiting self-powered wearable medical electronics by scavenging low-grade body heat.
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http://dx.doi.org/10.1021/acsami.1c12443DOI Listing
August 2021

Lignin-based adsorbent-catalyst with high capacity and stability for polychlorinated aromatics removal.

Bioresour Technol 2021 Oct 24;337:125453. Epub 2021 Jun 24.

School of Energy and Environmental Engineering, Hebei University of Technology, Tianjin 300401, China.

The utilization of lignin as carbonaceous material for pollution adsorption provides an alternative way for lignocellulose valorization. Here in, lignin-based adsorbents (i.e., LC-A, LC-B, and LC-C) were prepared and used for the removal of o-DCB (a toxic gaseous pollutant). LC-B exhibited the best adsorption capacity (718.2 mg/g) when comparing with LC-A (93.1 mg/g), LC-C (10.2 mg/g), and activated carbon (72.7 mg/g). LC-B also demonstrated excellent recycling stability with the adsorption capacity of 710.8 mg/g after five runs. More importantly, LC-B supported Ru adsorbent catalyst could effectively remove o-DCB with removal rate >80% under a wide range of temperature (50-300°C). The excellent performance of lignin-based adsorbents could be attributed to its abundant pore structure, high specific surface area (1618.55 m/g), enhanced graphitization degree as well as the abundant hydroxyl functional groups. The present work provided a cost-effective strategy for pollution control by lignin-based material.
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http://dx.doi.org/10.1016/j.biortech.2021.125453DOI Listing
October 2021

MA Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma.

Cancer Res 2021 Sep 23;81(18):4778-4793. Epub 2021 Jul 23.

Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

N-methyladenosine (mA) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important mA demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC). Regulation of PD-L1 expression by ALKBH5 was confirmed in human ICC cell lines. Sequencing of the mA methylome identified PD-L1 mRNA as a direct target of mA modification whose levels were regulated by ALKBH5. Furthermore, ALKBH5 and PD-L1 mRNA were shown to interact. ALKBH5 deficiency enriched mA modification in the 3'UTR region of PD-L1 mRNA, thereby promoting its degradation in a YTHDF2-dependent manner. and , tumor-intrinsic ALKBH5 inhibited the expansion and cytotoxicity of T cells by sustaining tumor cell PD-L1 expression. The ALKBH5-PD-L1-regulating axis was further confirmed in human ICC specimens. Single-cell mass cytometry analysis unveiled a complex role of ALKBH5 in the tumor immune microenvironment by promoting the expression of PD-L1 on monocytes/macrophages and decreasing the infiltration of myeloid-derived suppressor-like cells. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with strong nuclear expression patterns of ALKBH5 are more sensitive to anti-PD1 immunotherapy. Collectively, these results describe a new regulatory mechanism of PD-L1 by mRNA epigenetic modification by ALKBH5 and the potential role of ALKBH5 in immunotherapy response, which might provide insights for cancer immunotherapies. SIGNIFICANCE: This study identifies PD-L1 mRNA as a target of ALKBH5 and reveals a role for ALKBH5 in regulating the tumor immune microenvironment and immunotherapy efficacy.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0468DOI Listing
September 2021

MoCpa1-mediated arginine biosynthesis is crucial for fungal growth, conidiation, and plant infection of Magnaporthe oryzae.

Appl Microbiol Biotechnol 2021 Aug 22;105(14-15):5915-5929. Epub 2021 Jul 22.

Fujian Universities Key Laboratory for Plant-Microbe Interaction, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Arginine is an important amino acid involved in processes such as cell signal transduction, protein synthesis, and sexual reproduction. To understand the biological roles of arginine biosynthesis in pathogenic fungi, we used Cpa1, the carbamoyl phosphate synthase arginine-specific small chain subunit in Saccharomyces cerevisiae as a query to identify its ortholog in the Magnaporthe oryzae genome and named it MoCpa1. MoCpa1 is a 471-amino acid protein containing a CPSase_sm_chain domain and a GATase domain. MoCpa1 transcripts were highly expressed at the conidiation, early-infection, and late-infection stages of the fungus. Targeted deletion of the MoCPA1 gene resulted in a ΔMocpa1 mutant exhibiting arginine auxotrophy on minimum culture medium (MM), confirming its role in de novo arginine biosynthesis. The ΔMocpa1 mutant presented significantly decreased sporulation with some of its conidia being defective in morphology. Furthermore, the ΔMocpa1 mutant was nonpathogenic on rice and barley leaves, which was a result of defects in appressorium-mediated penetration and restricted invasive hyphal growth within host cells. Addition of exogenous arginine partially rescued conidiation and pathogenicity defects on the barley and rice leaves, while introduction of the MoCPA1 gene into the ΔMocpa1 mutant fully complemented the lost phenotype. Further confocal microscopy examination revealed that MoCpa1 is localized in the mitochondria. In summary, our results demonstrate that MoCpa1-mediated arginine biosynthesis is crucial for fungal development, conidiation, appressorium formation, and infection-related morphogenesis in M. oryzae, thus serving as an attractive target for mitigating obstinate fungal plant pathogens. KEY POINTS: • MoCpa1 is important for aerial hyphal growth and arginine biosynthesis. • MoCpa1 is pivotal for conidial morphogenesis and appressorium formation. • MoCpa1 is crucial for full virulence in M. oryzae.
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http://dx.doi.org/10.1007/s00253-021-11437-1DOI Listing
August 2021

Association of anemia and COVID-19 in hospitalized patients.

Future Virol 2021 Jun 8. Epub 2021 Jul 8.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, 1277 Jiefang Ave., Wuhan, China.

COVID-19 is a major threat to public health worldwide. A large proportion of COVID-19 patients is proved to develop anemia. Herein, we investigate the association between anemia and severe pneumonia. 137 of COVID-19-confirmed patients admitted to Wuhan Union Hospital (Wuhan, China) from 13 February to 17 March 2020 were included. Their clinical characteristics and laboratory data were studied, and multivariable logistic regression analyses were performed. The anemic patients were less likely to develop fever in the early stage of COVID-19. Elevated IL-6 levels were found in anemic COVID-19 patients compared with those without anemia. COVID-19 patients with anemia had an 8.2 times greater possibility of developing severe pneumonia compared with their counterparts without anemia. This study comprehensively describes the clinical characteristics of anemic patients with ordinary, severe and critical COVID-19 and demonstrates the close relationship between the anemia and severe COVID-19.
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http://dx.doi.org/10.2217/fvl-2021-0044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270514PMC
June 2021

Chemical Vapor Deposition of N-Doped Graphene through Pre-Implantation of Nitrogen Ions for Long-Term Protection of Copper.

Materials (Basel) 2021 Jul 5;14(13). Epub 2021 Jul 5.

College of Physics and Materials Science, Tianjin Normal University, Tianjin 300387, China.

Nitrogen-doped graphene (NG) was synthesized through the chemical vapor deposition (CVD) of graphene on Cu substrates, which were pre-implanted with N ions by the ion implantation method. The pre-implanted N ions in the Cu substrate could dope graphene by the substitution of C atoms during the CVD growth of graphene, forming NG. Based on this, NG's long-term protection properties for Cu were evaluated by ambient exposure for a corrosion test. The results showed that NG can obviously reduce the natural oxidation of Cu in the long-term exposure compared with the case of pristine graphene (PG) coated on Cu. Moreover, with the increase in pre-implanted N dose, the formed NG's long-term protection for Cu improved. This indicates that the modification of graphene by N doping is an effective way to improve the corrosion resistance of the PG coating owing to the reduction in its conductivity, which would inhibit galvanic corrosion by cutting off electron transport across the interface in their long-term protection. These findings provide insight into corrosion mechanisms of the graphene coating and correlate with its conductive nature based on heteroatoms doping, which is a potential route for improving the corrosion resistance of graphene as an effective barrier coating for metals.
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http://dx.doi.org/10.3390/ma14133751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269794PMC
July 2021

Selective autophagy controls the stability of TBK1 via NEDD4 to balance host defense.

Cell Death Differ 2021 Jul 13. Epub 2021 Jul 13.

Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.

As a core kinase of antiviral immunity, the activity and stability of TANK-binding kinase 1 (TBK1) is tightly controlled by multiple post-translational modifications. Although it has been demonstrated that TBK1 stability can be regulated by ubiquitin-dependent proteasome pathway, it is unclear whether another important protein degradation pathway, autophagosome pathway, can specifically affect TBK1 degradation by cargo receptors. Here we report that E3 ubiquitin ligase NEDD4 functions as a negative regulator of type I interferon (IFN) signaling by targeting TBK1 for degradation at the late stage of viral infection, to prevent the host from excessive immune response. Mechanically NEDD4 catalyzes the K27-linked poly-ubiquitination of TBK1 at K344, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, our study reveals the regulatory role of NEDD4 in balancing TBK1-centered type I IFN activation and provides insights into the crosstalk between selective autophagy and antiviral signaling.
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http://dx.doi.org/10.1038/s41418-021-00833-9DOI Listing
July 2021

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study.

Nat Sci Sleep 2021 29;13:989-1000. Epub 2021 Jun 29.

Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), 238000, People's Republic of China.

Background: To distinguish insomnia comorbid with depression (ICD) from chronic insomnia disorder (CID) by exploring the relationship between serum levels of frequently overlooked anti-inflammatory cytokines and cognitive function.

Methods: A total of 42 ICD patients, 63 CID patients, and 42 healthy control subjects were enrolled in the study. The Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale were used to assess sleep quality and depression severity, respectively. The Chinese-Beijing version of Montreal Cognitive Assessment scale (MoCA-C) and Nine-Box Maze Test (NBMT) were used to assess cognitive function. Serum levels of anti-inflammatory interleukins (IL-1RA, IL-4, IL-5, IL-10, IL-13, and IL-28A), transforming growth factor (TGF)-β1, granulocyte-macrophage colony-stimulating factor, interferon-γ, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES) were measured by enzyme-linked immunosorbent assay.

Results: The ICD group had significantly more errors in the spatial reference task (H=2.55, P=0.03) and spatial working memory task (H=5.67, P<0.01) of the NBMT, as well as lower levels of IL-1RA (H=-2.85, P=0.01), IL-4 (H=-3.28, P<0.01), IL-5 (H=-3.35, P<0.01), IL-10 (H=-4.46, P<0.01), and IL-28A (H=-2.75, P=0.02) than control subjects. Compared with the CID group, the ICD group had significantly more errors in the spatial reference memory task (H=-2.84, P=0.01) of the NBMT, and lower levels of IL-5 (H=3.41, P<0.01), IL-10 (H=5.30, P<0.01), IL-13 (H=3.89, P<0.01), and GM-CSF (H=2.72, P=0.02). A partial correlation analysis showed that the level of one or more of IL-4, IL-5, IL-10, IL-13, and TGF-β1 was positively correlated with cognitive function (MoCA-C score and/or performance in spatial memory task) in ICD patients.

Conclusion: ICD is a distinct condition that can be distinguished from CID based on immune dysfunction and specific types of cognitive dysfunction.
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http://dx.doi.org/10.2147/NSS.S312272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254552PMC
June 2021

Artificial intelligence for prediction of COVID-19 progression using CT imaging and clinical data.

Eur Radiol 2021 Jul 5. Epub 2021 Jul 5.

School of Computer Science and Engineering, Central South University, Changsha, China.

Objectives: Early recognition of coronavirus disease 2019 (COVID-19) severity can guide patient management. However, it is challenging to predict when COVID-19 patients will progress to critical illness. This study aimed to develop an artificial intelligence system to predict future deterioration to critical illness in COVID-19 patients.

Methods: An artificial intelligence (AI) system in a time-to-event analysis framework was developed to integrate chest CT and clinical data for risk prediction of future deterioration to critical illness in patients with COVID-19.

Results: A multi-institutional international cohort of 1,051 patients with RT-PCR confirmed COVID-19 and chest CT was included in this study. Of them, 282 patients developed critical illness, which was defined as requiring ICU admission and/or mechanical ventilation and/or reaching death during their hospital stay. The AI system achieved a C-index of 0.80 for predicting individual COVID-19 patients' to critical illness. The AI system successfully stratified the patients into high-risk and low-risk groups with distinct progression risks (p < 0.0001).

Conclusions: Using CT imaging and clinical data, the AI system successfully predicted time to critical illness for individual patients and identified patients with high risk. AI has the potential to accurately triage patients and facilitate personalized treatment.

Key Point: • AI system can predict time to critical illness for patients with COVID-19 by using CT imaging and clinical data.
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http://dx.doi.org/10.1007/s00330-021-08049-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256200PMC
July 2021

MicroRNA-29b participates in the epithelial-mesenchymal transition of retinal pigment epithelial cells through p-p65.

Exp Ther Med 2021 Aug 13;22(2):868. Epub 2021 Jun 13.

Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai 200072, P.R. China.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is considered to be the main mechanism of proliferative vitreoretinopathy (PVR). Our previous study demonstrated that microRNA-29b (miR-29b) and its target protein kinase B (Akt2) played vital roles in this process. miR-29b, a mesenchymal marker α-smooth muscle actin (α-SMA) and the epithelial marker E-cadherin were assessed in epiretinal membranes of patients with PVR. The potential mechanism of miR-29b and EMT was also investigated. The expression levels of miR-29b, E-cadherin, and α-SMA in PVR epiretinal membranes were measured using quantitative PCR. The expression levels of Akt2, phosphorylated (p)-Akt2, p65, p-p65, and Snail in ARPE-19 cells were assessed using western blotting. The expression levels of miR-29b were positively correlated with E-cadherin mRNA expression, while an inverse correlation was observed between miR-29b and α-SMA mRNA expression in epiretinal membranes of patients with PVR. When miR-29b was transfected into ARPE-19 cells, the expression levels of Akt2, p-Akt2, p-p65 and Snail were downregulated. shRNA-Akt2 inhibited p-p65 and Snail expression, while the NF-κB inhibitor BAY11-7082 reduced Snail expression. The Akt2/p-p65/Snail pathway may be the underlying mechanism of miR-29b in EMT of RPE cells. The results of the present study may provide a new strategy for prevention and therapy of PVR.
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http://dx.doi.org/10.3892/etm.2021.10300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237392PMC
August 2021

A gain-of-function NLRP3 3'-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression.

Sci Rep 2021 06 25;11(1):13300. Epub 2021 Jun 25.

The Key Laboratory of Sepsis Translational Medicine, The Intensive Care Unit, The Second Affiliated Hospital of Guangdong Medical University, Minyou Road 12, Xiashan District, Zhanjiang City, 524001, Guangdong Province, People's Republic of China.

Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3'-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3'-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.
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http://dx.doi.org/10.1038/s41598-021-92547-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233413PMC
June 2021

Characteristics of high-resolution magnetic resonance vessel wall imaging of cervicocerebral artery dissection and the influential factors of vascular recanalization.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 May;46(5):467-474

Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008, China.

Objectives: Cervicocerebral artery dissection (CAD) is one of the important causes for ischemic stroke in young and middle-aged people. CAD is dangerous and untimely diagnosis and treatment are likely to result in severe disability. Early diagnosis and timely intervention can greatly improve the prognosis of patients. This study was to investigate the imaging features of CAD on high-resolution magnetic resonance vessel wall imaging (HRMR-VWI) and to analyze the influential factors of vascular recanalization.

Methods: A total of 19 CAD patients with both baseline HRMR-VWI and follow-up data of vascular imaging in the period from April 2017 to December 2019 in Department of Radiology, Xiangya Hospital, Central South University were retrospectively analyzed. The diseased vessels were divided into a recovery group and a unrecovered group. After treatment, diseased vessels with no residual arterial dissection and no residual stenosis in the lumen were included in the recovery group. Diseased vessels with stenosis, occlusion or residual dissection were included in the unrecovered group. Diseased vessels were divided into a ischemic stroke group and a non-ischemic stroke group according to the presence or absence of ischemic stroke in the area supplied by the diseased vessels. Differences in clinical data and HRMR-VWI imaging findings were compared between the groups.

Results: A total of 26 vessels were involved, including 14 (53.8%) internal carotid artery extracranial segment, 8 (30.8%) vertebral artery extracranial segment, 3 (11.5%) vertebral artery intracranial segment, and 1 (3.9%) basilar artery. Ischemic stroke occurred in 16 diseased vascular supply areas. Intramural hematoma was all observed in the baseline HMR-VWI of the affected vessels. There were 18 vessels (69.2%) in the recovery group and 8 vessels (30.8%) in the unrecovered group. Compared with the vessels in the recovery group, the vessels in the unrecovered group were mostly found in the intracranial segment (<0.05). However, there were no significant differences in gender, age, imaging findings of dissection, length of lesion involvement, time between reexamination, vascular occlusion, and antiplatelet therapy between the recovery group and the unrecovered group (all >0.05).There were nosignificant differences in age, gender, complication of hypertension, hyperlipidemia, diabetes mellitus, lesion location, vascular occlusion, lesion involvement length, double lumen sign, internal membrane, and lumen thrombosis between the ischemic stroke group and the non-ischemic stroke group (all >0.05).

Conclusions: Intramural hematoma is a common imaging manifestation of CAD and can be shown clearly and accurately on HRMR-VWI. Recanalization rate of CAD is high, and the recanalization of CAD in intracranial segment is slower than that of CAD in extracranial segment, which can prolong the review time.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200154DOI Listing
May 2021

Exosomal MATN3 of Urine-Derived Stem Cells Ameliorates Intervertebral Disc Degeneration by Antisenescence Effects and Promotes NPC Proliferation and ECM Synthesis by Activating TGF-.

Oxid Med Cell Longev 2021 27;2021:5542241. Epub 2021 May 27.

Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, China 266003.

Objective: Low back pain (LBP) is one of the top three causes of disability in developed countries, and intervertebral disc degeneration (IDD) is a major contributor to LBP. In the process of IDD, there is a gradual decrease in nucleus pulposus cells (NPCs) and extracellular matrix (ECM). Exosomes are important exocrine mediators of stem cells that can act directly on cells for tissue repair and regeneration. In this study, we determined the antisenescence, cell proliferation promotion, and ECM modulation effects of human urine-derived stem cell (USC) exosomes (USC-exos) on degenerated intervertebral discs and explored the underlying mechanism.

Methods And Materials: USCs were identified by multipotent differentiation and flow cytometry for mesenchymal stem cell- (MSC-) specific surface protein markers. USC-exos were isolated from the conditioned medium of USCs by ultracentrifugation and then analyzed by transmission electron microscopy (TEM), particle size analysis, and western blotting (WB) for exosome marker proteins. The effects of USC-exos on NPC proliferation and ECM synthesis were assessed by Cell Counting Kit-8 (CCK-8), WB, and immunofluorescence (IF) analyses. The protein differences between normal and degenerative intervertebral discs were mined, and the temporal and spatial variations in matrilin-3 (MATN3) content were determined by WB and IF in the intervertebral disc tissues. The candidate molecules that mediated the function of USC-exos were screened out and confirmed by multiple assays. Meanwhile, the mechanism underlying the candidate protein in USC-exos-induced cell proliferation and regulation of ECM synthesis promoting the activities of NPCs was explored. In addition, the effects of USC-exos on ameliorating intervertebral disc degeneration (IVD) in mice were examined by assessing computed tomography (CT), magnetic resonance imaging (MRI), and histological analyses.

Results: The flow cytometry results showed that USCs were positive for CD29, CD44, and CD73, which are USC surface-specific markers, but negative for CD34 and CD45. In addition, USCs showed osteogenic, adipogenic, and chondrogenic differentiation potential. USC-exos exhibited a cup-shaped morphology, with a mean diameter of 49.7 ± 7.3 nm, and were positive for CD63 and TSG101 and negative for calnexin. USC-exos could promote NPC proliferation and ECM synthesis. The protein content of the matrilin family was significantly reduced in degenerative intervertebral discs, and the decrease in MATN3 was the most significant. USC-exos were found to be rich in MATN3 protein, and exosomal MATN3 was required for USC-exos-induced promotion of NPC proliferation and ECM synthesis, as well as alleviation of intervertebral disc degeneration in IVD rats. In addition, the effects of MATN3 in USC-exos were demonstrated to be achieved by activating TGF-, which elevated the phosphorylation level of SMAD and AKT.

Conclusions: Our study suggests that reduced MATN3 can be considered a characteristic of intervertebral disc degeneration. USC-exos may represent a potentially effective agent for alleviating intervertebral disc degeneration by promoting NPC proliferation and ECM synthesis by transferring the MATN3 protein.
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http://dx.doi.org/10.1155/2021/5542241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175180PMC
May 2021

The Exocyst Regulates Hydrolytic Enzyme Secretion at Hyphal Tips and Septa in the Banana Fusarium Wilt Fungus Fusarium odoratissimum.

Appl Environ Microbiol 2021 08 11;87(17):e0308820. Epub 2021 Aug 11.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry Universitygrid.256111.0, Fuzhou, China.

Hyphal polarized growth in filamentous fungi requires tip-directed secretion, while additional evidence suggests that fungal exocytosis for the hydrolytic enzyme secretion can occur at other sites in hyphae, including the septum. In this study, we analyzed the role of the exocyst complex involved in the secretion in the banana wilt fungal pathogen Fusarium odoratissimum. All eight exocyst components in not only localized to the tips ahead of the Spitzenkörper in growing hyphae but also localized to the outer edges of septa in mature hyphae. To further analyze the exocyst in , we attempted single gene deletion for all the genes encoding the eight exocyst components and only succeeded in constructing the gene deletion mutants for and ; we suspect that the other 6 exocyst components are encoded by essential genes. Deletion of or led to defects in vegetative growth, conidiation, and pathogenicity in . Notably, the deletion of resulted in decreased activities for endoglucosidase, filter paper enzymes, and amylase, while the loss of only led to a slight reduction in amylase activity. Septum-localized α-amylase (AmyB) was identified as the marker for septum-directed secretion, and we found that Exo70 is essential for the localization of AmyB to septa. Meanwhile the loss of Sec5 did not affect AmyB localization to septa but led to a higher accumulation of AmyB in cytoplasm. This suggested that while Exo70 and Sec5 both take part in the septum-directed secretion, the two play different roles in this process. The exocyst complex is a multisubunit tethering complex (MTC) for secretory vesicles at the plasma membrane and contains eight subunits, Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84. While the exocyst complex is well defined in eukaryotes from yeast () to humans, the exocyst components in filamentous fungi show different localization patterns in the apical tips of hyphae, which suggests that filamentous fungi have evolved divergent strategies to regulate endomembrane trafficking. In this study, we demonstrated that the exocyst components in Fusarium odoratissimum are localized not only to the tips of growing hyphae but also to the outer edge of the septa in mature hyphae, suggesting that the exocyst complex plays a role in the regulation of septum-directed protein secretion in . We further found that Exo70 and Sec5 are required for the septum-directed secretion of α-amylase in but with different influences.
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http://dx.doi.org/10.1128/AEM.03088-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357298PMC
August 2021

KeMRE: Knowledge-enhanced medical relation extraction for Chinese medicine instructions.

J Biomed Inform 2021 08 10;120:103834. Epub 2021 Jun 10.

Department of Electronic Engineering & BNRist, Tsinghua University, Beijing 100084, China. Electronic address:

Medicine instructions usually contain rich medical relations, and extracting them is very helpful for many downstream tasks such as medicine knowledge graph construction and medicine side-effect prediction. Existing relation extraction (RE) methods usually predict relations between entities from their contexts and do not consider medical knowledge. However, understanding a part of medical relations may need some expert knowledge in the medical field, making it challenging for existing methods to achieve satisfying performances of medical RE. In this paper, we propose a knowledge-enhanced framework for medical RE, which can exploit medical knowledge of medicines to better conduct medical RE on Chinese medicine instructions. We first propose a BERT-CNN-LSTM based framework for text modeling and learn representations of characters from their contexts. Then we learn representations of each entity by aggregating representations of their characters. Besides, we propose a CNN-LSTM based framework for entity modeling and learn entity representations from their relatedness. In addition, there are usually many different instructions for the same medicine, which usually share general knowledge on this medicine. Thus, to obtain medical knowledge of medicines, we annotate relations on a randomly-sampled instruction of each medicine. Then we build knowledge embeddings to represent potential relations between entities from knowledge of medicines. Finally, we use an MLP network to predict relations between entities from their representations and knowledge embeddings. Extensive experiments on a real-world dataset show that our method can significantly outperform existing methods.
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http://dx.doi.org/10.1016/j.jbi.2021.103834DOI Listing
August 2021

Engineering Gac/Rsm Signaling Cascade for Optogenetic Induction of the Pathogenicity Switch in .

ACS Synth Biol 2021 06 2;10(6):1520-1530. Epub 2021 Jun 2.

Hefei National Laboratory for Physical Sciences at the Microscale; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, China.

Bacterial pathogens operate by tightly controlling the pathogenicity to facilitate invasion and survival in host. While small molecule inducers can be designed to modulate pathogenicity to perform studies of pathogen-host interaction, these approaches, due to the diffusion property of chemicals, may have unintended, or pleiotropic effects that can impose limitations on their use. By contrast, light provides superior spatial and temporal resolution. Here, using optogenetics we reengineered GacS of the opportunistic pathogen , signal transduction protein of the global regulatory Gac/Rsm cascade which is of central importance for the regulation of infection factors. The resultant protein (termed YGS24) displayed significant light-dependent activity of GacS kinases in . When introduced in the host systems, YGS24 stimulated the pathogenicity of the strain PAO1 in a brain-heart infusion and of another strain, PA14, in slow killing media progressively upon blue-light exposure. This optogenetic system provides an accessible way to spatiotemporally control bacterial pathogenicity in defined hosts, even specific tissues, to develop new pathogenesis systems, which may in turn expedite development of innovative therapeutics.
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http://dx.doi.org/10.1021/acssynbio.1c00075DOI Listing
June 2021

Genome-wide identification, phylogenetic analysis, and expression analysis of the SPL gene family in orchardgrass (Dactylis glomerata L.).

Genomics 2021 Jul 28;113(4):2413-2425. Epub 2021 May 28.

College of Grassland Science and Technology, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

SPL (SQUAMOSA promoter binding protein-like) is a plant-specific transcription factor family that contains the conserved SBP domain, which plays a vital role in the vegetative-to-reproductive phase transition, flowering development and regulation, tillering/branching, and stress responses. Although the SPL family has been identified and characterized in various plant species, limited information about it has been obtained in orchardgrass, which is a critical forage crop worldwide. In this study, 17 putative DgSPL genes were identified among seven chromosomes, and seven groups that share similar gene structures and conserved motifs were determined by phylogenetic analysis. Of these, eight genes have potential target sites for miR156. cis-Element and gene ontology annotation analysis indicated DgSPLs may be involved in regulating development and abiotic stress responses. The expression patterns of eight DgSPL genes at five developmental stages, in five tissues, and under three stress conditions were determined by RNA-seq and qRT-PCR. These assays indicated DgSPLs are involved in vegetative-to-reproductive phase transition, floral development, and stress responses. The transient expression analysis in tobacco and heterologous expression assays in yeast indicated that miR156-targeted DG1G01828.1 and DG0G01071.1 are nucleus-localized proteins, that may respond to drought, salt, and heat stress. Our study represents the first systematic analysis of the SPL family in orchardgrass. This research provides a comprehensive assessment of the DgSPL family, which lays the foundation for further examination of the role of miR156/DgSPL in regulating development and stress responses in forages grasses.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.032DOI Listing
July 2021

Refractory Kawasaki disease: modified methylprednisolone regimen decreases coronary artery dilatation.

Pediatr Res 2021 May 21. Epub 2021 May 21.

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.

Background: The use of corticosteroids in Kawasaki disease (KD) is still controversial. The aim of this study was to investigate the safety and effectiveness of modified methylprednisolone (mPSL) regimen as an initial treatment for refractory KD.

Methods: This is a real-world observational study. We identified refractory KD with a self-developed scoring system. Patients were divided into the intravenous immunoglobulin (IVIG) + mPSL group and the IVIG group. Clinical outcomes and changes in coronary arteries after the treatment during a 12-week period were observed. Propensity-score matching was used to analyze those patients with similar baseline characteristics.

Results: Of a total of 168 patients, 104 patients were assigned into the IVIG group and 64 patients into the IVIG + mPSL group. The therapeutic response rate of the IVIG + mPSL group was significantly higher than that of the IVIG group (98.4 vs 76.0%, P < 0.05). The IVIG + mPSL group had a shorter duration of fever and a higher rate of C-reactive protein decline than the IVIG group (1.17 ± 0.64 vs 1.81 ± 1.16 days; 88.1 vs 83.5%; P < 0.05). The luminal diameter and Z-score of the left circumflex coronary artery (LCX) were significantly smaller and lower in the IVIG + mPSL group than that in the IVIG group at weeks 2 and 12.

Conclusions: Modified mPSL regimen has minimal side effects. It might improve the initial response to IVIG and decrease the dilation of LCX for refractory KD.

Impact: Modified mPSL regimen (2-4 mg/kg/day, divided into 2-3 doses for 3-5 days, then 1 mg/kg/day, once a day for 3-5 days, then oral prednisone was tapered over 3-5 weeks in 5-7 days steps) as an intensive initial treatment can decrease LCX dilation in high-risk IVIG-resistant KD patients. Our self-developed scoring system has been proven validated and can be used to identify high-risk IVIG-resistant KD patients in North China. The present study provides an alternative therapeutic regimen for high-risk refractory KD patients.
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http://dx.doi.org/10.1038/s41390-021-01576-6DOI Listing
May 2021

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome.

Nat Commun 2021 05 18;12(1):2915. Epub 2021 May 18.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.

Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2 mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.
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http://dx.doi.org/10.1038/s41467-021-23201-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131593PMC
May 2021
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