Publications by authors named "Ge Zhang"

836 Publications

Prognostic Relevance of Structural Maintenance of Chromosomes 4 Overexpression in Pediatric Acute Lymphoblastic Leukemia.

Clin Lab 2022 Jan;68(1)

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Abnormal expression of structural maintenance of chromosomes (SMC) 4 has been observed in multiple tumors and plays a vital role in cancer development. However, the association between SMC4 expression and clinical characteristics in Chinese childhood patients with ALL is unknown. Thus, this study aimed to investigate the relationship between SMC4 expression and clinical features and prognosis in these patients.

Methods: Real-time quantitative polymerase chain reaction (PCR) was performed to detect the expression of SMC4 in Chinese pediatric ALL patients and in patients achieving complete remission (CR). Then, the relationships between SMC4 expression and clinical features, such as gender, age, white blood cell (WBC) count, French-American-British (FAB) classification, immunophenotype, fusion gene, prednisone response, and minimal residual disease (MRD) were determined. Furthermore, survival and prognostic factor analyses were carried out to examine the prognostic value of SMC4 expression.

Results: The expression level of SMC4 was significantly higher in bone morrow cells of newly diagnosed pediatric ALL patients than in those of healthy controls (p = 0.006), especially in B-cell precursor ALL (BCP ALL). Moreover, SMC4 expression was correlated with different clinical parameters. Furthermore, a decrease of SMC4 expression was detected in BCP ALL patients achieving CR. The high SMC4 expression group had both worse event-free survival rate and poorer overall survival rate. However, multivariate analysis showed that SMC4 expression was not an independently predictive factor of BCP ALL outcome.

Conclusions: These results revealed that SMC4 expression in BM was associated with various clinical outcomes in pediatric patients with ALL, although it was not an independent outcome factor.
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http://dx.doi.org/10.7754/Clin.Lab.2021.210852DOI Listing
January 2022

Safinamide protects against amyloid β (Aβ)-induced oxidative stress and cellular senescence in M17 neuronal cells.

Bioengineered 2022 01;13(1):1921-1930

Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang City, China.

Alzheimer's disease (AD) is a neurodegenerative disorder that is pathologically related to oxidative stress and cellular senescence. Safinamide is one of the clinically prescribed monoamine oxidase B (MAOB) inhibitors. It has been reported to possess therapeutic potential in neurological disorders. However, the therapeutic potential of safinamide in AD is still under investigation. In this study, we explored the effect of safinamide in amyloid (Aβ) oligomers-stimulated M17 neuronal cells. We established the in vitro model with M17 cells by treating them with 1 μM Aβ oligomers with or without safinamide (100 or 200 nM). The results show that safinamide ameliorated Aβ oligomers-induced oxidative stress in M17 cells as revealed by the decreased reactive oxygen species (ROS) production and reduced glutathione (GSH) content. Safinamide treatment significantly ameliorated senescence-associated-β-galactosidase (SA-β-gal)-positive cells and telomerase activity. Further, we show that safinamide treatment resulted in decreased mRNA and protein expressions of p21 and plasminogen activator inhibitor-1 (PAI-1). Moreover, silencing of Sirtuin1 (SIRT1) abolished the effects of safinamide on the mRNA levels of p21 and PAI-1, as well as SA-β-gal-positive cells in Aβ oligomers-induced M17 cells. In conclusion, we reveal that safinamide exerted a protective function on M17 cells from Aβ oligomers induction-caused oxidative stress and cellular senescence through SIRT1 signaling. These present results provide meaningful evidence that safinamide may be medically developed for the prevention and therapy of AD.
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http://dx.doi.org/10.1080/21655979.2021.2022262DOI Listing
January 2022

Circular RNA circ_0002984 promotes cell proliferation and migration by regulating miR-181b-5p/VEGFA axis and PI3K-AKT signaling pathway in ox-LDL-treated VSMCs.

J Cardiovasc Pharmacol 2021 Dec 22. Epub 2021 Dec 22.

Department of Geriatric Neurology, Heilongjiang Provincial Hospital, Haerbin City, Heilongjiang Province, China; Department of Cardiology, Heilongjiang Provincial Hospital, Haerbin City, Heilongjiang Province, China.

Abstract: Circular RNAs (circRNAs) play critical roles in many diseases, including atherosclerosis (AS). However, the role and underlying mechanism of circ_0002984 in AS remain unclear. Vascular smooth muscle cells (VSMCs) treated with oxidized low-density lipoprotein (ox-LDL) were used as a AS cell model. Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression of circ_0002984, miR-181b-5p and vascular endothelial growth factor A (VEGFA). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell migration was assessed using wound healing assay and transwell assay. All protein levels were analyzed by western blot (WB) assay. The interaction between miR-181b-5p and circ_0002984 or VEGFA was confirmed by dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. Circ_0002984 and VEGFA were overexpressed and miR-181b-5p was downregulated in serum of AS patients and ox-LDL-stimulated VSMCs. Circ_0002984 silencing inhibited ox-LDL-induced proliferation and migration in VSMCs. MiR-181b-5p was a target of circ_0002984, and miR-181b-5p inhibition counteracted the suppressing effects of circ_0002984 downregulation on proliferation and migration in ox-LDL-stimulated VSMCs. Additionally, VEGFA was a downstream target of miR-181b-5p, and VEGFA upregulation abolished the suppressive influence of miR-181b-5p on proliferation and migration in ox-LDL-exposed VSMCs. Further, circ_0002984 depletion blocked PI3K-AKT signaling pathway by regulating miR-181b-5p and VEGFA. Circ_0002984 downregulation suppressed cell proliferation and migration by regulating miR-181b-5p/VEGFA axis and PI3K-AKT pathway in ox-LDL-stimulated VEGFA, providing a new mechanism for AS pathogenesis.
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http://dx.doi.org/10.1097/FJC.0000000000001203DOI Listing
December 2021

Molecular Coupling and Self-Assembly Strategy toward WSe /Carbon Micro-Nano Hierarchical Structure for Elevated Sodium-Ion Storage.

Small Methods 2021 Aug 30;5(8):e2100374. Epub 2021 Jun 30.

Functional Thin Films Research Center, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Sodium (Na) ion-based dual-ion batteries (Na-DIBs) have attracted great attention, owing to their benefits of low cost, high working voltage, and environmental friendliness. However, the limited capacity and low tap density of currently reported anode materials restrict the further improvement of Na-DIBs. Herein, a micro-nano structure with vertically aligned WSe nanoflakes anchored tightly on a micron-sized carbon sphere (WSe /CS) is successfully constructed via combining the molecular coupling and self-assembly strategy. Within this hierarchical structure, the WSe nanoflakes can shorten the diffusion path for Na ions and alleviate structural deformation during the charge/discharge process; meanwhile, the micron-sized carbon core provides conductive support and helps improve the total tap density of the anode electrode. As a result, this micron-sized WSe /CS displays a high specific capacity of ≈252.8 mAh g and good cycling performance with ≈92% capacity retention after 1200 cycles. Moreover, by pairing this WSe /CS anode with environmental friendly graphite as cathode, a proof-of-concept Na-DIB shows 85.6% capacity retention after 1000 cycles, which is among the best performances of previously reported Na-DIBs.
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http://dx.doi.org/10.1002/smtd.202100374DOI Listing
August 2021

Offering soybean molasses adsorbed to agricultural by-products improved lactation performance through modulating plasma metabolic enzyme pool of lactating cows.

Food Sci Nutr 2021 Dec 13;9(12):6447-6457. Epub 2021 Oct 13.

Feng Yi (Shanghai) Biotechnology R&D Center co. LTD Shanghai China.

Background: Agricultural by-products, such as corncob powder (CRP), wheat bran (WB), rice husk (RH), defatted bran (DB), and soybean hulls (SH), were widely used as ruminant feed. However, the combination effect of soybean molasses mixed with agricultural by-products on cow lactating performance remains poorly understood.

Methods: fermentation simulation technique was used to select the high ruminal fermentation performance of agricultural by-products mixed with soybean molasses. The selected mixtures were conducted to further explore the feeding effect on milk performance and blood metabolic enzyme on lactating dairy cows.

Results: In simulation, it was confirmed that SH-SM showed better fermentation performance (including higher maximum gas production, acetate, propionate, and total VFA, but less initial fractional rate of degradation) than other four molasses-adsorbents, while WB-SM had the greatest DM and NDF disappearance and NH3-N and butyrate concentrations among substrates. After the simulation selection, we performed the feed experiment with SH-SM and WB-SM compared to the control. For lactating performance, higher ( < .01) milk fat and total milk solid content were observed in WB-SM, and a tendency improvement of milk protein content ( < .01) was observed in both of the cows fed with WB-SM and SH-SM. Among lactating periods, the blood glutamic-pyruvic transaminase, α-amylase, and lactate dehydrogenase which associated with amino acid metabolism and carbohydrate metabolism were improved in lactating dairy cows fed with WB-SM and SH-SM.

Conclusion: Dietary agricultural by-products (like wheat bran and soybean hulls) mixed with soybean molasses enhance the lactating performance of dairy cows by improving the host metabolism process of amino acids and carbohydrates. The mixed strategy for agricultural by-products shows another strong evidence for the resource reuse on dairy industry and reducing the by-product pollution.
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http://dx.doi.org/10.1002/fsn3.2504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645711PMC
December 2021

[MRI/TRUS cognitive fusion combined with 12-core systematic transperineal prostate biopsy for the diagnosis of clinically significant prostate cancer: A report of 208 cases].

Zhonghua Nan Ke Xue 2021 May;27(5):421-425

Department of Urology, Changshu Second People's Hospital / the 5th School of Clinical Medicine of Yangzhou University, Changshu, Jiangsu 215500, China.

Objective: To investigate the detection rate and complications of magnetic resonance imaging / transrectal ultrasonography (MRI/TRUS) cognitive fusion combined with 12-core systematic transperineal prostate biopsy (TPPB) in the diagnosis of clinically significant PCa (CS-PCa).

Methods: This retrospective study included 208 patients undergoing first-time MRI/TRUS cognitive fusion combined with 12-core systematic TPPB from June 2015 to May 2019. The patients, aged 54-85 (67.6 ± 7.8) years, all received digital rectal examination, PSA detection, TRUS and prostate multiparametric MRI (mpMRI) before biopsy. We analyzed the mpMRI images, identified and marked the suspected signal areas, repeated TRUS for further observation of the prostate, conducted cognitive fusion based on the mpMRI images and determined the target before 12-core systematic TPPB and subjecting the samples obtained to pathological examination.

Results: Of the 208 patients, 112 were diagnosed with CS-PCa (no case with tPSA < 4 μg/L, 21 cases with 4 μg/L ≤ tPSA < 10 μg/L, 47 cases with 10 μg/L ≤ tPSA < 20 μg/L, 40 cases with 20 μg/L ≤ tPSA < 100 μg/L, and 4 cases with tPSA ≥ 100 μg/L), 85 with BPH, 8 with chronic prostatitis, 2 with atypical prostatic hyperplasia, and 1 with prostatic intraepithelial neoplasia. Systemic inflammatory response syndrome occurred in 3 and gross hematuria and/or bloody stool in 12 cases after biopsy, which were all cured by anti-infection and hemostasis treatment.

Conclusions: MRI/TRUS cognitive fusion combined with 12-core systematic transperineal prostate biopsy can improve the detection rate of the initial diagnosis of clinically significant PCa with a low incidence of controllable complications.
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May 2021

Readiness for hospital discharge in primary caregivers for children with acute lymphoblastic leukaemia.

J Clin Nurs 2021 Dec 7. Epub 2021 Dec 7.

West China Second University Hospital, Sichuan University, Chengdu, China.

Aim: To investigate existing status and factors affecting the readiness for hospital discharge in primary caregivers for children with acute lymphoblastic leukaemia in China.

Background: Acute lymphoblastic leukaemia is the most common childhood cancer, but there is not enough research on the readiness for hospital discharge.

Design: A cross-sectional study was performed by convenience sampling and questionnaire survey.

Methods: A self-developed questionnaire of general and clinical characteristics of patients, self-developed questionnaire of general status of family and primary caregivers, questionnaire of readiness of hospital discharge scale and social support rating scale for primary caregivers were delivered to 264 primary caregivers of childhood acute lymphoblastic leukaemia patients. Data collection was carried out 24 h before discharge at bedside. In this study, the STROBE checklist was followed.

Results: In total, 253 patients aged 0-16 years, including their primary caregivers in the hospital, were included from November 2016 to August 2017. Based on the readiness scale, the total mean score of readiness was 157.36. Based on the social support scale, the total mean score was 42.17. According to multivariate analysis, periods of chemotherapy (p < .001), complications (p = .019), family economic situation (p = .023), understanding of leukaemia (p < .001), objective support (p = .004), subjective support (p < .001) and availability of support (p = .045) were the main influencers of readiness.

Conclusions: The readiness for hospital discharge in primary caregivers for childhood lymphoblastic leukaemia patients is not satisfactory in China.

Relevance To Clinical Practice: This study has implications for public health administration, asking for better community services and disease education. In addition, more effort should be made to provide high-quality family and primary caregiver assessments and discharge education by nurses.
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http://dx.doi.org/10.1111/jocn.16159DOI Listing
December 2021

Phosphate Group-Derivated Bipyridine-Ruthenium Complex and Titanium Dioxide Nanoparticles for Electrochemical Sensing of Protein Kinase Activity.

ACS Sens 2021 Dec 6;6(12):4451-4460. Epub 2021 Dec 6.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, People's Republic of China.

Monitoring of protein kinase activity is of significance for fundamentals of biochemistry, biomedical diagnose, and drug screening. To reduce the usage of a relatively complicated bio-labeled signal probe, the phosphate group-derivated bipyridine-ruthenium (Pbpy-Ru) complex and titanium dioxide nanoparticles (TiO NPs) were employed as signal probes to develop an electrochemical sensor for evaluating the protein kinase A (PKA) activity. Through the specific interaction between the phosphate groups and TiO NPs, the preparation of a Pbpy-Ru-TiO NP signal probe and its linkage with the phosphorylated PKA substrate peptides could be performed in a simple and effective way. The tethering of Pbpy-Ru onto the TiO NP surface does not degrade the electrochemical property of the complex. The Pbpy-Ru-TiO NP probe exhibits well-defined redox signals at about 1.0 V versus Ag/AgCl reference and notably has about fivefold current response than that of the TiO NPs with physically adsorbed tris-(bipyridine)-Ru. The PKA activity evaluation was realized by measuring the electrochemical response of the Pbpy-Ru-TiO NPs at the phosphorylated peptide-assembled electrode. Operating at optimal conditions, the cathodic signals at the potential of 1.03 V exhibit a good linearity with the PKA concentrations of 0.5-40 U mL. The electrochemical sensor shows good selectivity, low detection limit (0.2 U mL, signal/noise = 3), qualified reproducibility, and satisfactory applicability for PKA determination in the cell lysate. The Pbpy-Ru-TiO NPs/electrode system would be an excellent electrochemical platform for protein phosphorylation monitoring and sensing.
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http://dx.doi.org/10.1021/acssensors.1c01908DOI Listing
December 2021

Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer.

Cell Death Discov 2021 Dec 4;7(1):375. Epub 2021 Dec 4.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo. Studies have confirmed that higher concentrations of ROS leads to autophagy or cell death. In this research, the role of CC90003-induced ROS was verified. But after inhibiting ROS by two kinds of ROS inhibitors NAC and SFN, the autophagy induced by CC90003 decreased, while cell death strengthened. In parallel, protective autophagy was also induced, while in a p53-dependent manner. After silencing p53 or using the p53 inhibitor PFTα, the autophagy induced by CC90003 was weakened and the rate of cell death increases. Therefore, we confirmed that CC90003 could induce autophagy by activating ROS/p53. Furthermore, in the xenograft mouse model, the effect was obtained remarkably in the combinational treatment group of CC90003 plus CQ, comparing with that of the single treatment groups. In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for clinical therapy.
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http://dx.doi.org/10.1038/s41420-021-00677-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643355PMC
December 2021

Can Native Plants Mitigate Climate-related Forage Dearth for Honey Bees (Hymenoptera: Apidae)?

J Econ Entomol 2021 Nov 25. Epub 2021 Nov 25.

Department of Entomology, Iowa State University, Ames, IA 50011, USA.

Extreme weather events, like high temperatures and droughts, are predicted to become common with climate change, and may negatively impact plant growth. How honey bees (Apis mellifera L. [Hymenoptera: Apidae]) will respond to this challenge is unclear, especially when collecting pollen, their primary source of protein, lipids, and micro-nutrients. We explored this response with a data set from multiple research projects that measured pollen collected by honey bees during 2015-2017 in which above-average temperatures and a drought occurred in 2017. We summarized the abundance and diversity of pollen collected from July to September in replicated apiaries kept at commercial soybean and corn farms in Iowa, in the Midwestern USA. The most commonly collected pollen was from clover (Trifolium spp. [Fabales: Fabaceae]), which dramatically declined in absolute and relative abundance in July 2017 during a period of high temperatures and drought. Due to an apparent lack of clover, honey bees switched to the more drought-tolerant native species (e.g., Chamaecrista fasciculata [Michx.] Greene [Fabales: Fabaceae], Dalea purpurea Vent. [Fabales: Fabaceae], Solidago spp. [Asterales: Asteraceae]), and several species of Asteraceae. This was especially noticeable in August 2017 when C. fasciculata dominated (87%) and clover disappeared from bee-collected pollen. We discuss the potential implications of climate-induced forage dearth on honey bee nutritional health. We also compare these results to a growing body of literature on the use of native, perennial flowering plants found in Midwestern prairies for the conservation of beneficial insects. We discuss the potential for drought resistant-native plants to potentially promote resilience to climate change for the non-native, managed honey bee colonies in the United States.
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http://dx.doi.org/10.1093/jee/toab202DOI Listing
November 2021

Progress, Opportunities, and Challenges of Troponin Analysis in the Early Diagnosis of Cardiovascular Diseases.

Anal Chem 2022 01 29;94(1):442-463. Epub 2021 Nov 29.

State Key Laboratory of Biogeology Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

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http://dx.doi.org/10.1021/acs.analchem.1c04476DOI Listing
January 2022

Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Isolates With High MIC Values.

Front Cell Infect Microbiol 2021 29;11:739496. Epub 2021 Oct 29.

Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

() is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on , and further research is required for its more in-depth characterization and analysis. Eleven strains of collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in . All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06-0.12 μg/ml), posaconazole (0.06-0.12 μg/ml), amphotericin B (0.25-1 μg/ml), and 5-flucytosine (range, <0.06-0.12 μg/ml), whereas four isolates showed high MICs (≥4 μg/ml) for echinocandins. Strains with high MIC values for azoles showed common mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of . In addition, one new amino acid alteration, I1348S (I1368), was found outside of the hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.
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http://dx.doi.org/10.3389/fcimb.2021.739496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586209PMC
November 2021

In Vivo Ultrasound Localization Microscopy Imaging of the Kidney's Microvasculature with Block-matching 3D Denoising.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Nov 2;PP. Epub 2021 Nov 2.

Structural abnormalities and functional changes of renal microvascular networks play a significant pathophysiologic role in the occurrence of kidney diseases. Super-resolution ultrasound imaging has been successfully utilized to visualize the microvascular network and provide valuable diagnostic information. To prevent the burst of microbubbles, a lower mechanical index (MI) is generally used in ultrasound localization microscopy (ULM) imaging. However, high-noise levels lead to incorrect signal localizations in relatively low-MI settings and deep tissue. In this study, we implemented a block-matching threedimensional (BM3D) image-denoising method, after the application of singular value decomposition filtering, to further suppress the noise at various depths. The in vitro flow-phantom results show that the BM3D method helps the significant reduction of the error localizations, thus improving the localization accuracy. In vivo rhesus macaque experiments help conclude that the BM3D method improves the resolution more than other image-based denoising techniques, such as the nonlocal means method. The obtained clutter-filtered images with fewer incorrect localizations can enable robust ULM imaging, thus helping in establishing an effective diagnostic tool.
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http://dx.doi.org/10.1109/TUFFC.2021.3125010DOI Listing
November 2021

Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas.

Front Oncol 2021 12;11:672265. Epub 2021 Oct 12.

Department of Medical Imaging, Henan Provincial People's Hospital and The People's Hospital of Zhengzhou University, Zhengzhou, China.

Objectives: To explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.

Methods: A retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADC) and ADC under ultra-high values (ADC) ( values: 2500 to 5000 s/mm) were calculated based on monoexponential model. The fraction of fast diffusion (), pseudo ADC (ADC) and true ADC (ADC) were calculated by bi-exponential model ( values: 0 to 2000 s/mm). The apparent diffusional kurtosis (K) was derived from the simplified diffusion kurtosis imaging (DKI) model ( values: 200 to 3000 s/mm). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.

Results: The ADC and ADC at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADC, ADC and ADC at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. K showed a correlation with Ki-67 while no significant correlation with AQPs. ADC ( < 0.001) and ADC ( = 0.001) were significantly lower while the ADC ( = 0.006) and K ( = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADC, , ADC, ADC, ADC, K at the tumor center had significant differences with those in peritumor when the gliomas grade became high ( < 0.05). Involving ADC and K simultaneously into an independent ADC model (AUC = 0.833) could further improve the grading performance (ADC+ADC+K: AUC = 0.923).

Conclusion: Different DWI metrics fitted within different -value ranges (low to ultra-high values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.
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http://dx.doi.org/10.3389/fonc.2021.672265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546342PMC
October 2021

Longer Time Intervals From Symptom Onset to Diagnosis Affect the Overall Survival in Children With Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2021 Oct 26. Epub 2021 Oct 26.

Department of Laboratory Medicine, West China Second University Hospital, Sichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, China.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival.

Methods: This retrospective cohort study included 419 patients aged 0 to 14 years at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival.

Results: The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL.

Conclusions: These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.
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http://dx.doi.org/10.1097/MPH.0000000000002344DOI Listing
October 2021

A Method for Detecting Incipient Faults in Satellites Based on Dynamic Linear Discriminant Analysis.

Comput Intell Neurosci 2021 14;2021:1303936. Epub 2021 Oct 14.

Innovation Academy for Microsatellites of CAS, Shanghai 201203, China.

Timely detection and treatment of possible incipient faults in satellites will effectively reduce the damage and harm they could cause. Although much work has been done concerning fault detection problems, the related questions about satellite incipient faults are little addressed. In this paper, a new satellite incipient fault detection method was proposed by combining the ideas of deviation in unsupervised fault detection methods and classification in supervised fault detection methods. First, the proposed method uses dynamic linear discriminant analysis (LDA) to find an optimal projection vector that separates the in-orbit data from the normal historical data as much as possible. Second, under the assumption that the parameters obey a multidimensional Gaussian distribution, it applies the normal historical data and the optimal projection vector to build a normal model. Finally, it employs the noncentral -distribution to test whether a fault has occurred. The proposed method was validated using a numerical simulation case and a real satellite fault case. The results show that the method proposed in this paper is more effective at detecting incipient faults than traditional methods.
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http://dx.doi.org/10.1155/2021/1303936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531832PMC
October 2021

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

Int J Chron Obstruct Pulmon Dis 2021;16:2817-2832. Epub 2021 Oct 8.

Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) is a major health problem associated with high mortality worldwide. Cigarette smoke (CS) exposure is the main cause of COPD. Glioma pathogenesis-related protein 1 (GLIPR1) plays a key role in cell growth, proliferation, and invasion; however, the role of GLIPR1 in COPD remains unclear.

Methods: To clarify the involvement of GLIPR1 in COPD pathogenesis, Glipr1 knockout (Glipr1-/-) mice were generated. Wild-type (WT) and Glipr1-/- mice were challenged with CS for 3 months. To illustrate how GLIPR1 regulates CS-induced airway damage, knockdown experiments targeting GLIPR1 and PLAU, as well as overexpression experiments of PLAU, were performed with human bronchial epithelial cells.

Results: Compared with WT mice, Glipr1-/- mice showed exacerbated CS-induced airway damage including lung inflammation, airway wall thickening, and alveolar destruction. After CS exposure, total proteins, total white cells, neutrophils, lymphocytes, IL-6, and matrix metalloproteinase-9 increased significantly in lung of Glipr1-/- mice than those in lung of WT mice. Furthermore, in vivo and in vitro experiments demonstrated that silencing of GLIPR1 inactivated PLAU/EGFR signaling and promoted caspase-1-dependent pyroptosis (a mode of inflammatory cell death) induced by CS and CS extract exposure, respectively. In vitro experiments further revealed the interaction between GLIPR1 and PLAU, and silencing of PLAU blocked EGFR signaling and promoted pyroptosis, while overexpression of PLAU activated EGFR signaling and reversed pyroptosis.

Conclusion: To conclude, GLIPR1 played a pivotal role in COPD pathogenesis and protected against CS-induced inflammatory response and airway damage, including cell pyroptosis, through the PLAU/EGFR signaling. Thus, GLIPR1 may play a potential role in COPD treatment.
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http://dx.doi.org/10.2147/COPD.S328313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517531PMC
November 2021

How to Achieve Standardization? Diluted Russell Viper Venom Test for Lupus Anticoagulant Detection in a Chinese Female Population.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211048897

Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.

On an international scale, guidelines and proposals for lupus anticoagulant detection have been published over the last 20 years, but until now, standardization has not been completely realized. The aim of this study was to evaluate the different ways of interpreting the results of lupus anticoagulant detection for standardization. A retrospective review of 15 447 instances of lupus anticoagulant detection by the diluted Russell Viper Venom test for female patients presenting with problems relating to the areas of reproduction, gynecology and obstetrics was performed. Lupus anticoagulant data were compared between different departments, months, reagent lots and cutoffs. Significant differences were found in patient data between different reagent lots, especially between lots of screening reagents (monthly average: highest 37.96 s vs lowest 33.88 s) and in the positive rates of lupus anticoagulant by different detection cutoffs (47.58% by using LA1/LA2 > 1.20 without normalization as a cutoff in Lot 1 vs 1.52% by using LA1 > 44 s as a cutoff in Lot 3). Compared with the cutoff using the value above the 99th percentile of LA1 for the healthy donors per lot, the cutoff using integrated tests with normalization had the smaller deviation of positive rate between different reagent lots. Pregnant women had higher LA1/LA2 levels than nonpregnant women. Based on the results, normalization is needed because there are significant lot-to-lot variations. Integrated tests with normalization might be a better standard by which to confirm lupus anticoagulant. Pregnant women should have population-specific cutoffs because they have higher LA1/LA2 levels.
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http://dx.doi.org/10.1177/10760296211048897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521729PMC
October 2021

Targeting senescent immune cells to rejuvenate the aging skeleton.

Authors:
Ge Zhang Jin Liu

Cell Metab 2021 Oct;33(10):1903-1905

Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.

Accumulation of senescent cells in the bone marrow leads to age-related bone degeneration. Identifying the key senescent cell types and the factors they release that are responsible for skeletal aging is of keen interest. In a new study by Li et al. (2021), it is shown that immune cells, including neutrophils and macrophages, are critical cell types in this aging process, and that they secrete grancalcin to promote such aging.
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http://dx.doi.org/10.1016/j.cmet.2021.09.005DOI Listing
October 2021

Size effect of γ-MnO precoated anode on lead-containing pollutant reduction and its controllable fabrication in industrial-scale for zinc electrowinning.

Chemosphere 2022 Jan 2;287(Pt 4):132457. Epub 2021 Oct 2.

School of Environment, Tsinghua University, Beijing, 100084, China; State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai, 200092, China; State Environmental Protection Key Laboratory of Eco-Industry, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Lead (Pb) is the most widely used anode in zinc (Zn) electrowinning and other metallurgical industries. The resource loss and environmental pollution caused by Pb anode corrosion are urgent problems to be solved. A γ-MnO precoated anode was prepared successfully to reduce the Pb-containing pollutant. The size effects with its controllable preparation on an industrial scale were studied. Severe nonuniform distribution of γ-MnO film was observed with curbing the reduction of anode slime only 68%, when anode size increased from lab to industry. Nonuniform rate (R) and average thickness (d) were found to be the key indicators to determine the film structure distribution and their performance differences, which were random and difficult to be controlled in scale-up size. However, a controllable industrial γ-MnO precoated anodes (IMPA) fabricated through optimized current density (J) and electrodeposition time (t) in our developed film-forming system. Then, the long-term performances of two IMPA with different indicators (IMPA-1: R = 34%, d = 108 μm, IMPA-2: R = 23%, d = 55 μm) were compared with the industrial typical Pb-based anode (ITPA). Of the three different anodes, the optimized IMPA-2 displayed the best performance. Within 24 d of electrowinning cycle, the corrosion inhibition effect and the anode slime reduction rate for IMPA-2 improved by 56% and 30% than IMPA-1, and improved by 100% and 91% than ITPA. Furthermore, the mechanism analysis of size effect change showed that R of IMPA was contributed to the local gas holdup distribution along the anode. Controlled size effect of uniform oxide film will have a future application prospect for the sustainability of industry, which provides an important cleaner production of Zn electrowinning and related hydrometallurgy industries.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132457DOI Listing
January 2022

The Application of Microfluidic Technologies in Aptamer Selection.

Front Cell Dev Biol 2021 17;9:730035. Epub 2021 Sep 17.

Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong, SAR China.

Aptamers are sequences of single-strand oligonucleotides (DNA or RNA) with potential binding capability to specific target molecules, which are increasingly used as agents for analysis, diagnosis, and medical treatment. Aptamers are generated by a selection method named systematic evolution of ligands by exponential enrichment (SELEX). Numerous SELEX methods have been developed for aptamer selections. However, the conventional SELEX methods still suffer from high labor intensity, low operation efficiency, and low success rate. Thus, the applications of aptamer with desired properties are limited. With their advantages of low cost, high speed, and upgraded extent of automation, microfluidic technologies have become promising tools for rapid and high throughput aptamer selection. This paper reviews current progresses of such microfluidic systems for aptamer selection. Comparisons of selection performances with discussions on principles, structure, operations, as well as advantages and limitations of various microfluidic-based aptamer selection methods are provided.
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http://dx.doi.org/10.3389/fcell.2021.730035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484746PMC
September 2021

Performance Evaluation of the Gradient Diffusion Strip Method and Disk Diffusion Method for Ceftazidime-Avibactam Against and : A Dual-Center Study.

Front Microbiol 2021 16;12:710526. Epub 2021 Sep 16.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Ceftazidime-avibactam is a novel synthetic beta-lactam + beta-lactamase inhibitor combination. We evaluated the performance of the gradient diffusion strip method and the disk diffusion method for the determination of ceftazidime-avibactam against and Antimicrobial susceptibility testing of 302 clinical and isolates from two centers were conducted by broth microdilution (BMD), gradient diffusion strip method, and disk diffusion method for ceftazidime-avibactam. Using BMD as a gold standard, essential agreement (EA), categorical agreement (CA), major error (ME), and very major error (VME) were determined according to CLSI guidelines. CA and EA rate > 90%, ME rate < 3%, and VME rate < 1.5% were considered as acceptable criteria. Polymerase chain reaction and Sanger sequencing were performed to determine the carbapenem resistance genes of all 302 isolates. A total of 302 strains were enrolled, among which 182 strains were from center 1 and 120 strains were from center 2. A percentage of 18.21% (55/302) of the enrolled isolates were resistant to ceftazidime-avibactam. The CA rates of the gradient diffusion strip method for and were 100% and 98.65% (73/74), respectively, and the EA rates were 97.37% (222/228) and 98.65% (73/74), respectively. The CA rates of the disk diffusion method for and were 100% and 95.95% (71/74), respectively. No VMEs were found by using the gradient diffusion strip method, while the ME rate was 0.40% (1/247). No MEs were found by using the disk diffusion method, but the VME rate was 5.45% (3/55). Therefore, all the parameters of the gradient diffusion strip method were in line with acceptable criteria. For 31 , 33 , 7 , and 2 positive isolates, both CA and EA rates were 100%; no MEs or VMEs were detected by either method. For 15 carbapenemase-non-producing resistant isolates, the CA and EA rates of the gradient diffusion strips method were 100%. Whereas the CA rate of the disk diffusion method was 80.00% (12/15), the VME rate was 20.00% (3/15). The gradient diffusion strip method can meet the needs of clinical microbiological laboratories for testing the susceptibility of ceftazidime-avibactam drugs. However, the VME rate > 1.5% (5.45%) by the disk diffusion method. By comparison, the performance of the gradient diffusion strip method was better than that of the disk diffusion method.
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http://dx.doi.org/10.3389/fmicb.2021.710526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481768PMC
September 2021

A Satellite Incipient Fault Detection Method Based on Decomposed Kullback-Leibler Divergence.

Entropy (Basel) 2021 Sep 9;23(9). Epub 2021 Sep 9.

Innovation Academy for Microsatellites of CAS, Shanghai 201203, China.

Detection of faults at the incipient stage is critical to improving the availability and continuity of satellite services. The application of a local optimum projection vector and the Kullback-Leibler (KL) divergence can improve the detection rate of incipient faults. However, this suffers from the problem of high time complexity. We propose decomposing the KL divergence in the original optimization model and applying the property of the generalized Rayleigh quotient to reduce time complexity. Additionally, we establish two distribution models for subfunctions F1(w) and F3(w) to detect the slight anomalous behavior of the mean and covariance. The effectiveness of the proposed method was verified through a numerical simulation case and a real satellite fault case. The results demonstrate the advantages of low computational complexity and high sensitivity to incipient faults.
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http://dx.doi.org/10.3390/e23091194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472508PMC
September 2021

Cobalt-Catalyzed Radical Hydroamination of Alkenes with N-Fluorobenzenesulfonimides.

Angew Chem Int Ed Engl 2021 12 28;60(49):25949-25957. Epub 2021 Oct 28.

Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry, Northeast Normal University, Changchun, 130024, China.

An efficient and general radical hydroamination of alkenes using Co(salen) as catalyst, N-fluorobenzenesulfonimide (NFSI) and its analogues as both nitrogen source and oxidant was successfully disclosed. A variety of alkenes, including aliphatic alkenes, styrenes, α, β-unsaturated esters, amides, acids, as well as enones, were all compatible to provide desired amination products. Mechanistic experiments suggest that the reaction underwent a metal-hydride-mediated hydrogen atom transfer (HAT) with alkene, followed by a pivotal catalyst controlled S 2-like pathway between in situ generated organocobalt(IV) species and nitrogen-based nucleophiles. Moreover, by virtue of modified chiral cobalt(II)-salen catalyst, an unprecedented asymmetric version was also achieved with good to excellent level of enantiocontrol. This novel asymmetric radical C-N bond construction opens a new door for the challenging asymmetric radical hydrofunctionalization.
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http://dx.doi.org/10.1002/anie.202110178DOI Listing
December 2021

Maternal selenium levels and whole genome screen in recurrent spontaneous preterm birth population: A nested case control study.

Eur J Obstet Gynecol Reprod Biol 2021 Oct 18;265:203-211. Epub 2021 Aug 18.

Harris Wellbeing Preterm Birth Research Centre, Department of Women's and Children's Health, University of Liverpool, Liverpool Women's Hospital, Liverpool, United Kingdom.

Objective: To establish if low maternal selenium (Se) was associated with sPTB in women with recurrent sPTB and identify genetic link with maternal Se levels.

Design: Nested case-control study.

Setting: Tertiary Maternity Hospital.

Population: Plasma and whole blood from pregnant women with history of early sPTB/PPROM < 34 and European ancestry were obtained at 20 weeks (range 15-24 weeks). 'Cases' were recurrent PTB/PPROM < 34 weeks and term (≥37) deliveries were classified as 'high-risk controls.' Women with previous term births and index birth ≥ 39 weeks were 'low-risk controls'.

Methods: Maternal plasma Se measured by ICP-MS was used as a continuous phenotype in a GWAS analysis. Se was added to a logistic regression model using PTB predictor variables.

Main Outcome Measures: Maternal Se concentration, recurrent early sPTB/PPROM.

Results: 53/177 high-risk women had a recurrent sPTB/PPROM < 34weeks and were 2.7 times more likely to have a Se level < 83.3 ppm at 20weeks of pregnancy compared with low-risk term controls (n = 179), (RR 2.7, 95%CI 1.5-4.8; p = .001). One SNP from a non-coding region (FOXN3 intron variant, rs55793422) reached genome-wide significance level (p = 3.73E). Targeted analysis of Se gene variant did not show difference between preterm and term births. (χ test, OR = 0.95; 95%CI = 0.59-1.56; p = 0.82). When Se levels were added to a clinical prediction model, only an additional 5% of cases (n = 3) and 0.6% (n = 1) of controls were correctly identified.

Conclusions: Low plasma Se is associated with sPTB risk but is not sufficiently predictive at individual patient level. We did not find a genetic association between maternal Se levels and Se-related genes.
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http://dx.doi.org/10.1016/j.ejogrb.2021.08.015DOI Listing
October 2021

Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis.

BMJ Glob Health 2021 09;6(9)

Center for Public Health Kinetics, New Delhi, India.

Background: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.

Methods: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis.

Findings: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi.

Interpretation: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.
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http://dx.doi.org/10.1136/bmjgh-2021-005856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438754PMC
September 2021

Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS.

Front Immunol 2021 27;12:730483. Epub 2021 Aug 27.

Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China.

The antiviral innate immunity is the first line of host defense against viral infection. Mitochondrial antiviral signaling protein (MAVS, also named Cardif/IPS-1/VISA) is a critical protein in RNA virus-induced antiviral signaling pathways. Our previous research suggested that E3 ubiquitin-protein ligases RING-finger protein (RNF90) negatively regulate cellular antiviral responses by targeting STING for degradation, though its role in RNA virus infection remains unknown. This study demonstrated that RNF90 negatively regulated RNA virus-triggered antiviral innate immune responses in RNF90-silenced PMA-THP1 cells, RNF90-deficient cells (including HaCaTs, MEFs, and BMDMs), and RNF90-deficient mice. However, RNF90 regulated RNA virus-triggered antiviral innate immune responses independent of STING. RNF90 promoted K48-linked ubiquitination of MAVS and its proteasome-dependent degradation, leading to the inhibition of innate immune responses. Altogether, our findings suggested a novel function and mechanism of RNF90 in antiviral innate immunity.
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http://dx.doi.org/10.3389/fimmu.2021.730483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429505PMC
December 2021

Susceptibility to Imipenem/Relebactam of and Isolates from Chinese Intra-Abdominal, Respiratory and Urinary Tract Infections: SMART 2015 to 2018.

Infect Drug Resist 2021 31;14:3509-3518. Epub 2021 Aug 31.

Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Purpose: In recent years, less options are available for treating carbapenem-resistant and carbapenem-resistant . The present study investigates the susceptibility rates to imipenem/relebactam for the treatment of intra-abdominal infections (IAIs), respiratory tract infections (RTIs) and urinary tract infections (UTIs) caused by and in China.

Patients And Methods: A total of 1886 and 1889 isolates were collected in 21 centers (7 regions) as a part of the global SMART surveillance program between 2015 and 2018. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) recommendations using the broth microdilution methodology at Peking Union Medical College Hospital.

Results: For , overall susceptibility rates to imipenem/relebactam were 84.2% at a CLSI breakpoint of ≤2 mg/L compared to 55.7% for imipenem. Susceptibility rates of imipenem-non-susceptible to imipenem/relebactam were 64.4% and for multidrug-resistance (MDR) susceptibility rates were increased from 25.2% for imipenem to 65.8% for imipenem/relebactam. The susceptibilities of imipenem-non-susceptible and MDR strains were similarly restored by imipenem/relebactam in non-ICU and ICU wards. The rate of imipenem-non-susceptibilities isolates was 79.0%, whereas the MDR rate was 81.9%. Relebactam did not change the susceptibilities of imipenem-non susceptible or MDR isolates.

Conclusion: Imipenem/relebactam provides a therapy option to treat infections caused by MDR or imipenem-non-susceptible but not infections in China.
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http://dx.doi.org/10.2147/IDR.S325520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418378PMC
August 2021

Current Pharmacological Strategies for Duchenne Muscular Dystrophy.

Front Cell Dev Biol 2021 19;9:689533. Epub 2021 Aug 19.

School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Duchenne muscular dystrophy (DMD) is a lethal, X-linked neuromuscular disorder caused by the absence of dystrophin protein, which is essential for muscle fiber integrity. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. There is still no cure for DMD so far and the standard of care is principally limited to symptom relief through glucocorticoids treatments. Current therapeutic strategies could be divided into two lines. Dystrophin-targeted therapeutic strategies that aim at restoring the expression and/or function of dystrophin, including gene-based, cell-based and protein replacement therapies. The other line of therapeutic strategies aims to improve muscle function and quality by targeting the downstream pathological changes, including inflammation, fibrosis, and muscle atrophy. This review introduces the important developments in these two lines of strategies, especially those that have entered the clinical phase and/or have great potential for clinical translation. The rationale and efficacy of each agent in pre-clinical or clinical studies are presented. Furthermore, a meta-analysis of gene profiling in DMD patients has been performed to understand the molecular mechanisms of DMD.
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http://dx.doi.org/10.3389/fcell.2021.689533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417245PMC
August 2021
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