Publications by authors named "Feng Xu"

2,911 Publications

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HOXC10 suppresses browning to maintain white adipocyte identity.

Diabetes 2021 May 14. Epub 2021 May 14.

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore

Promoting beige adipocyte development within white adipose tissue (WAT) is a potential therapeutic approach to staunch the current obesity epidemic. Previously, we identified homeobox-containing transcription factor HOXC10 as a suppressor of browning in subcutaneous WAT. Here, we provide evidence for the physiological role of HOXC10 in regulating WAT thermogenesis. Analysis of an adipose-specific HOXC10 knockout mouse line with no detectable HOXC10 in mature adipocytes revealed spontaneous subcutaneous WAT browning, increased expression of genes involved in browning, increased basal rectal temperature, enhanced cold tolerance and improved glucose homeostasis. These phenotypes were further exacerbated by exposure to cold or a β-adrenergic stimulant. Mechanistically, cold and β-adrenergic exposure led to reduced HOXC10 protein level without affecting its mRNA level. Cold exposure induced PKA-dependent proteasome-mediated degradation of HOXC10 in cultured adipocytes and shotgun proteomics approach identified KCTD 2, 5 and 17 as potential E3 ligases regulating HOXC10 proteasomal degradation. Collectively, these data demonstrate that HOXC10 is a gatekeeper of WAT identity, and targeting HOXC10 could be a plausible therapeutic strategy to unlock WAT thermogenic potentials.
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http://dx.doi.org/10.2337/db21-0114DOI Listing
May 2021

Resistance elicited by sub-lethal concentrations of ampicillin is partially mediated by quorum sensing in Pseudomonas aeruginosa.

Environ Int 2021 May 11;156:106619. Epub 2021 May 11.

School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China; Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, Hangzhou 310012, China. Electronic address:

The rapid increase of antibiotic resistance is a serious challenge around the world. Antibiotics are present in various environments at sub-lethal concentrations, but how resistance emerges under sub-lethal conditions is not fully clear. In this study, we evolved Pseudomonas aeruginosa PAO1 under sub-lethal conditions, in the presence of either 15-30 μg/mL or 150-300 μg/mL of ampicillin. We found a ~ 5-6 fold increase in the minimum inhibitory concentration (MIC) among evolved isolates exposed to 15-30 μg/mL of ampicillin, and more than a 19-fold of increase in 150-300 μg/mL of ampicillin exposure. DNA sequencing revealed that mpl and ampD were frequently mutated in these resistant strains. We performed a transcriptome analysis of deletion mutations of mpl or ampD, compared to PAO1. Both showed a two-fold increase in expression of quorum sensing (QS) genes including lasR and rhlI/R; the heightened expression was positively correlated with the expression of the ampicillin resistance gene ampC. We queried if quorum sensing contributes to the increase in the ampicillin MIC. After adding the quorum quencher acylase I, the growth yield both decreased by roughly 50% for Δmpl in 2000 μg/mL of ampicillin and ΔampD in 4000 μg/mL of ampicillin. Addition of the QS signals into synthase mutants restored the higher MIC, but only for the rhlI/R circuit. This study highlights the involvement of QS in antibiotic resistance evolution, and shows the multifactorial contributors to the observed phenotypes.
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http://dx.doi.org/10.1016/j.envint.2021.106619DOI Listing
May 2021

Glycolysis-Based Genes Are Potential Biomarkers in Thyroid Cancer.

Front Oncol 2021 26;11:534838. Epub 2021 Apr 26.

Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

While increased glycolysis has been identified as a cancer marker and attracted much attention in thyroid cancer (THCA), the prognostic role of it remains to be further elucidated. Here we aimed to determine a specific glycolysis-associated risk model to predict THCA patients' survival. We also explored the interaction between this signature and tumor immune microenvironment and performed drug screening to identify specific drugs targeting the glycolysis-associated signature. Six genes (CHST6, POM121C, PPFIA4, STC1, TGFBI, and FBP2) comprised the specific model, which was an independent prognostic indicator in THCA patients determined by univariate, LASSO and multivariate Cox regression analyses. The receiver operating characteristic (ROC) curve analysis confirmed the excellent clinical performance of the prognostic signature. According to the specific gene signature, patients were categorized into high- and low-risk subgroups. The high-risk group was characterized by decreased immune score and elevated tumor purity, as well as worser survival prognosis compared to the low-risk group. We also validated the expression of these genes in clinical samples and experiments. Lastly, we identified potential drugs targeting the glycolysis-associated signature. The derived glycolysis-related signature is an independent prognostic biomarker for THCA patients and might be used as an efficacy of biomarker for drug-sensitivity prediction.
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http://dx.doi.org/10.3389/fonc.2021.534838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107473PMC
April 2021

Dexmedetomidine Protects Against Septic Liver Injury by Enhancing Autophagy Through Activation of the AMPK/SIRT1 Signaling Pathway.

Front Pharmacol 2021 26;12:658677. Epub 2021 Apr 26.

Department of Intensive Care Unit, Children's Hospital of Chongqing Medical University, Chongqing, China.

Liver injury is one of the serious complications of sepsis. Previous studies suggested that dexmedetomidine (DEX) could alleviate cecal ligation and puncture (CLP)-induced liver injury. However, it is unclear whether the protective effect of DEX on sepsis-induced liver injury is related to autophagy. Mice ( = 105) were randomly divided into the following groups: (i) CON group (Sham); (ii) CLP group (CLP-induced liver injury + saline); (iii) CLP + DEX group (CLP-induced liver injury + DEX). Mouse models of sepsis-induced liver injury were established using CLP. DEX or normal saline was administered by intraperitoneal injection at 0, 2, and 4 h after CLP surgery. The mortality rate within 120 h was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and inflammatory cytokines were measured at 6, 12, and 24 h in each group. Hematoxylin and eosin staining assay was carried out to detect the morphological changes of mouse liver cells in each group. The levels of autophagy-associated proteins LC3II, Beclin-1, p62, and LAMP-2 were detected in three groups of mice using western blotting. The expression of LC3II was detected using immunofluorescence. Transmission electron microscopy (TEM) of liver tissue was used to observe autophagosomes and autophagosome-lysosomes. Lastly, the effect of DEX on the AMPK/SIRT1 pathway-associated protein levels were detected using western blotting. Meanwhile, we used L0-2 cells infected with mRFP-GFP-LC3 adenovirus to further analyze the role of SIRT1 in DEX-induced autophagy in liver injury model . DEX significantly improved the survival rate of septic mice at the early stage and ameliorated the pathology of sepsis-induced liver injury. The level of autophagy-associated proteins, phosphorylated ()-AMPK/AMPK, and SIRT1 in the liver of CLP-induced sepsis mice peaked at 12 h post-CLP and decreased significantly at 24 h. In the CLP + DEX group, the levels of autophagy-associated proteins, -AMPK/AMPK, and SIRT1 increased, whereas inflammatory cytokines decreased at 24 h. The autophagosome structure was clearly observed at different time points in the CLP + DEX group. In the hepatocyte injury model, the SIRT1 inhibitor significantly increased intracellular ROS levels and reversed the effect of DEX on autophagy flux. We demonstrated a novel mechanism in which DEX protects against CLP-induced liver injury. DEX enhances autophagy, which alleviates the inflammatory responses in CLP-induced liver injury by regulating the SIRT1/AMPK pathway.
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http://dx.doi.org/10.3389/fphar.2021.658677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109052PMC
April 2021

Strain-Mediated Spin-Orbit Torque Enhancement in Pt/Co on Flexible Substrate.

ACS Nano 2021 May 10. Epub 2021 May 10.

School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.

Current-induced magnetization switching by spin-orbit torque generated in heavy metals offers an enticing realm for energy-efficient memory and logic devices. The spin Hall efficiency is a key parameter in describing the generation of spin current. Recent findings have reported enhancement of spin Hall efficiency by mechanical strain, but its origin remains elusive. Here, we demonstrate a 45% increase in spin Hall efficiency in the platinum/cobalt (Pt/Co) bilayer, of which 78% of the enhancement was preserved even after the strain was removed. Spin transparency and X-ray magnetic circular dichroism revealed that the enhancement was attributed to a bulk effect in the Pt layer. This was further confirmed by the linear relationship between the spin Hall efficiency and resistivity, which indicates an increase in skew-scattering. These findings shed light on the origin of enhancement and are promising in shaping future utilization of mechanical strain for energy-efficient devices.
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http://dx.doi.org/10.1021/acsnano.0c09404DOI Listing
May 2021

Agreement of Angiography-Derived and Wire-Based Fractional Flow Reserves in Percutaneous Coronary Intervention.

Front Cardiovasc Med 2021 23;8:654392. Epub 2021 Apr 23.

Department of Cardiology, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Coronary angiography-derived fractional flow reserve (caFFR) measurements have shown good correlations and agreement with invasive wire-based fractional flow reserve (FFR) measurements. However, few studies have examined the diagnostic performance of caFFR measurements before and after percutaneous coronary intervention (PCI). This study sought to compare the diagnostic performance of caFFR measurements against wire-based FFR measurements in patients before and after PCI. Patients who underwent FFR-guided PCI were eligible for the acquisition of caFFR measurements. Offline caFFR measurements were performed by blinded hospital operators in a core laboratory. The primary endpoint was the vessel-oriented composite endpoint (VOCE), defined as a composite of vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization. A total of 105 pre-PCI caFFR measurements and 65 post-PCI caFFR measurements were compared against available wire-based FFR measurements. A strong linear correlation was found between wire-based FFR and caFFR measurements ( = 0.77; < 0.001) before PCI, and caFFR measurements also showed a high correlation ( = 0.82; < 0.001) with wire-based FFR measurements after PCI. A total of 6 VOCEs were observed in 61 patients during follow-up. Post-PCI FFR values (≤0.82) in the target vessel was the strongest predictor of VOCE [hazard ratio (HR): 5.59; 95% confidence interval (CI): 1.12-27.96; = 0.036). Similarly, patients with low post-PCI caFFR values (≤0.83) showed an 8-fold higher risk of VOCE than those with high post-PCI caFFR values (>0.83; HR: 8.83; 95% CI: 1.46-53.44; = 0.017). The study showed that the caFFR measurements were well-correlated and in agreement with invasive wire-based FFR measurements before and after PCI. Similar to wire-based FFR measurements, post-PCI caFFR measurements can be used to identify patients with a higher risk for adverse events associated with PCI.
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http://dx.doi.org/10.3389/fcvm.2021.654392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102686PMC
April 2021

Artificial intelligence in gastroenterology and hepatology: Status and challenges.

World J Gastroenterol 2021 Apr;27(16):1664-1690

Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, Zhejiang Province, China.

Originally proposed by John McCarthy in 1955, artificial intelligence (AI) has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images. Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology. This review will illustrate AI technology procedures for medical image analysis, including data processing, model establishment, and model validation. Furthermore, we will summarize AI applications in endoscopy, radiology, and pathology, such as detecting and evaluating lesions, facilitating treatment, and predicting treatment response and prognosis with excellent model performance. The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation, ethics and legal concerns, and the incomprehensibility of the output results. Therefore, doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.
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http://dx.doi.org/10.3748/wjg.v27.i16.1664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072192PMC
April 2021

Metal-Bridged Graphene-Protein Supraparticles for Analog and Digital Nitric Oxide Sensing.

Adv Mater 2021 May 7:e2007900. Epub 2021 May 7.

School of Chemistry and Chemical Engineering and Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200241, China.

Self-limited nanoassemblies, such as supraparticles (SPs), can be made from virtually any nanoscale components, but SPs from nanocarbons including graphene quantum dots (GQDs), are hardly known because of the weak van der Waals attraction between them. Here it is shown that highly uniform SPs from GQDs can be successfully assembled when the components are bridged by Tb ions supplementing van der Waals interactions. Furthermore, they can be coassembled with superoxide dismutase, which also has weak attraction to GQDs. Tight structural integration of multilevel components into SPs enables efficient transfer of excitonic energy from GQDs and protein to Tb . This mechanism is activated when Cu is reduced to Cu by nitric oxide (NO)-an important biomarker for viral pulmonary infections and Alzheimer's disease. Due to multipronged fluorescence enhancement, the limit of NO detection improves 200 times reaching 10 × 10 m. Furthermore, the uniform size of SPs enables digitization of the NO detection using the single particle detection format resulting in confident registration of as few as 600 molecules mL . The practicality of the SP-based assay is demonstrated by the successful monitoring of NO in human breath. The biocompatible SPs combining proteins, carbonaceous nanostructures, and ionic components provide a general path for engineering uniquely sensitive assays for noninvasive tracking of infections and other diseases.
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http://dx.doi.org/10.1002/adma.202007900DOI Listing
May 2021

Cannabidiol Protects Human Skin Keratinocytes from Hydrogen-Peroxide-Induced Oxidative Stress via Modulation of the Caspase-1-IL-1β Axis.

J Nat Prod 2021 May 6. Epub 2021 May 6.

Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, United States.

Preclinical and clinical studies support cannabidiol (CBD)'s antioxidant and anti-inflammatory effects, which are linked to its skin protective effects, but there have been limited mechanistic studies reported. Herein we evaluated CBD's protective effects against hydrogen peroxide (HO)-induced oxidative stress in human keratinocyte HaCaT cells and explored its possible mechanism(s) of action. CBD (10 μM) protected HaCaT cells by alleviating HO (200 μM)-induced cytotoxicity (by 11.3%) and reactive oxygen species (total- and mitochondrial-derived). Several NLRP3 inflammasome-related genes including and were identified as potential molecular targets for CBD's antioxidant effects by multiplexed gene and network pharmacology analyses. CBD treatment down-regulated the mRNA expression levels of and (by 32.9 and 51.0%, respectively) and reduced IL-1β level (by 16.2%) in HO-stimulated HaCaT cells. Furthermore, CBD inhibited the activity of caspase-1 enzyme (by 15.7%) via direct binding to caspase-1 protein, which was supported by data from a biophysical binding assay (surface plasmon resonance) and a computational docking experiment. In addition, CBD mitigated HO-induced pyroptosis (capase-1-mediated cell death) and apoptosis by 23.6 and 44.0%, respectively. The findings from the current study suggest that CBD exerts protective effects in human keratinocytes via the modulation of the caspase-1-IL-1β axis, supporting its potential skin health applications.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00083DOI Listing
May 2021

Head-to-Tail Oligomerization by Silylene-tethered Sonogashira Coupling on Ag(111).

Angew Chem Int Ed Engl 2021 May 5. Epub 2021 May 5.

National Institute for Materials Science (NIMS), Research Center for Advanced Measurement and Characterization, Sengen 1-2-1, 305-0047, Tsukuba, JAPAN.

On-surface synthesis is a powerful methodology for the fabrication of π-conjugated nanomaterials. Here, we demonstrate chemoselective Sonogashira coupling between trimethylsilyl(TMS)ethynyl and chloropheny groups in silylethynyl- and chloro-substituted partially fluorinated phenylene-ethynylenes (SiCPFPEs) on Ag(111). The desilylative Sonogashira coupling achieved a high chemoselectivity up to 75% while the competing homo-couplings of Ullmann and desilylative Glaser couplings were suppressed. A combination of bond-resolved scanning tunnelling microscopy/atomic force microscopy (STM/AFM) and density functional theory calculations revealed that the oligomers were obtained by the formation of intermolecular silylene-tethers (-Me 2 Si-) via the CH 3 -Si bond activation at 130 °C and the subsequent elimination of the tethers at an elevated temperature of 200 °C.
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http://dx.doi.org/10.1002/anie.202102882DOI Listing
May 2021

Differentially Expressed Long Noncoding RNAs Involved in FUBP1 Promoting Hepatocellular Carcinoma Cells Proliferation.

Biomed Res Int 2021 14;2021:6664519. Epub 2021 Apr 14.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 Zhejiang, China.

Background: Far upstream element-binding protein 1 (FUBP1) is reported to be involved in cancer development by regulating the transcription of c-myc gene through binding to far upstream element. Highly expressed FUBP1 was negatively correlated with survival rate of patients with hepatocellular carcinoma (HCC) and could promote the proliferation of HCC cells. However, the downstream mechanism of FUBP1 has not yet been clearly explained. This study is aimed at identifying the expression profiles of long noncoding RNA (lncRNA) in HCC cells in response to FUBP1 overexpression and at investigating the possible lncRNAs that participated in cell proliferation process regulated by FUBP1.

Methods: The overexpression of FUBP1 was mediated by lentiviral infection on 3 different types of HCC cell lines (MHCC97-H, MHCC97-L, and Huh-7). The expression of target genes was detected by quantitative reverse transcription-PCR (RT-PCR) and western blotting assays. Microarray and quantitative RT-PCR were applied to screen the differentially expressed lncRNAs in HCC cells after FUBP1 overexpression. The Cell Counting Kit-8 assay was used to confirm the growth vitality of HCC cells.

Results: The growth vitality of HCC cells was significantly increased after lentivirus infection. A total of 12 lncRNAs had the same expression trend in the 3 HCC cell lines in response to FUBP1 overexpression, including 3 upregulated lncRNAs and 9 downregulated lncRNAs. Coexpression analysis of dysregulated lncRNAs-mRNAs network showed that lnc-LYZ-2 was the lncRNA most relevant to FUBP1. Inhibition of lnc-LYZ-2 could significantly relieve the proproliferation effect of FUBP1 on HCC cells, suggesting that lnc-LYZ-2 was partially involved in proproliferation regulation of FUBP1.

Conclusions: Our results indicated that FUBP1 induced the abnormal expression of lncRNAs and the FUBP1-lncRNAs coexpression network in HCC cells, which could provide theoretical and experimental basis for FUBP1-lncRNAs network involved in HCC development.
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http://dx.doi.org/10.1155/2021/6664519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063849PMC
April 2021

Efficient management strategy of COVID-19 patients based on cluster analysis and clinical decision tree classification.

Sci Rep 2021 05 5;11(1):9626. Epub 2021 May 5.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, National Clinical Research Center for Respiratory Diseases, Beijing, 100029, China.

Early classification and risk assessment for COVID-19 patients are critical for improving their terminal prognosis, and preventing the patients deteriorate into severe or critical situation. We performed a retrospective study on 222 COVID-19 patients in Wuhan treated between January 23rd and February 28th, 2020. A decision tree algorithm has been established including multiple factor logistic for cluster analyses that were performed to assess the predictive value of presumptive clinical diagnosis and features including characteristic signs and symptoms of COVID-19 patients. Therapeutic efficacy was evaluated by adopting Kaplan-Meier survival curve analysis and cox risk regression. The 222 patients were then clustered into two groups: cluster I (common type) and cluster II (high-risk type). High-risk cases can be judged from their clinical characteristics, including: age > 50 years, chest CT images with multiple ground glass or wetting shadows, etc. Based on the classification analysis and risk factor analysis, a decision tree algorithm and management flow chart were established, which can help well recognize individuals who needs hospitalization and improve the clinical prognosis of the COVID-19 patients. Our risk factor analysis and management process suggestions are useful for improving the overall clinical prognosis and optimize the utilization of public health resources during treatment of COVID-19 patients.
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http://dx.doi.org/10.1038/s41598-021-89187-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100107PMC
May 2021

Comprehensive Interventions Including Vitamin D Effectively Reduce the Risk of Falls in Elderly Osteoporotic Patients.

Orthop Surg 2021 May 5. Epub 2021 May 5.

Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Objective: To evaluate the effects of different intervention measures to prevent falls in elderly osteoporotic patients.

Methods: A randomized controlled trial was conducted in our outpatient ward from August 2014 to September 2015. A total of 420 patients over 60 years of age were assigned to four groups. NA VitD group took 800 mg calcium and 800 IU non-active vitamin D. P-NA VitD group took 800 mg calcium, 800 IU non-active vitamin D, and received physical exercise. A VitD group took 800 mg calcium and 0.5 μg active vitamin D. P-A VitD took 800 mg calcium, 0.5 μg active vitamin D, and received physical exercise. Physical exercise includes guidance in improving muscle strength and balance ability. Short physical performance battery (SPPB), grip strength, modified falls efficacy scale (MFES), blood calcium, and 25-hydroxyl vitamin D were measured before interventions and at 3, 6, and 12 months after interventions. Bone mineral density (BMD) was detected before interventions and at 12 months after interventions. The incidence of falls and fractures, adverse events, and drug reactions were recorded for 12 months.

Results: A total of 420 patients were allocated in the four groups: 98 cases into the NA VitD group (11 males, 87 females), 97 cases into the P-NA VitD group (13 males, 84 females), 99 cases in the A VitD group (15 males, 84 females), and 98 cases into the P-A VitD group (11 males, 87 females). At 6 months after interventions, the SPPB of A VitD group significantly increased from 6.9 ± 1.9 to 8.0 ± 2.4 (P < 0.05), and the SPPB of A VitD group significantly increased from 7.2 ± 2.1 to 8.6 ± 1.7 (P < 0.05). At 6 months after interventions, MFES of P-NA VitD group 7.0 ± 1.6 to 7.6 ± 1.6 (P < 0.05), and MFES of P-A VitD group significantly increased from 6.7 ± 1.6 to 7.5 ± 1.6 (P < 0.05). At 12 months after interventions, SPPB of all groups, grip strength, and MFES of P-NA VitD group, A VitD group, P-A VitD group were significantly improved (P < 0.05). The BMD of lumbar vertebrae of A VitD group significantly increased from 0.742 ± 0.042 to 0.776 ± 0.039, and P-A VitD group significantly increased from 0.743 ± 0.048 to 0.783 ± 0.042 (P < 0.05). No serious adverse events occurred during the 12 months of follow-up.

Conclusion: Active vitamin D is better than non-active vitamin D to improve physical ability and the BMD of lumbar vertebrae and reduce the risk of falls.
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http://dx.doi.org/10.1111/os.13009DOI Listing
May 2021

Establishment of a population pharmacokinetics model of vancomycin in 94 infants with septicemia and its application in individualized therapy.

BMC Pharmacol Toxicol 2021 May 4;22(1):26. Epub 2021 May 4.

Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Putuo District, Shanghai, 200062, China.

Background: We aim to develop a population pharmacokinetics (PopPK) model of vancomycin for the treatment of septicemia in infants younger than one year. Factors influence of the PK was investigated to optimize vancomycin dosing regimen.

Methods: The nonlinear mixed effects modelling software (NONMEM) was used to develop the PopPK model of vancomycin. The stability and predictive ability of the final model were assessed by using normalized prediction distribution errors (NPDE) and bootstrap methods. The final model was subjected to Monte Carlo simulation in order to determine the optimal dose.

Results: A total of 205 trough and peak concentrations in 94 infants (0-1 year of age) with septicemia were analyzed. The interindividual variability of the PK parameter was described by the exponential model. Residual error was better described by the proportional model than the mixed proportional and addition models. Serum creatinine concentration and body weight are the major factors that affect the PK parameters of vancomycin. The clearance was shown to be higher when ceftriaxone was co-treated. More than two model evaluation methods showed better stability than the base model, with superior predictive performance, which can develop individualized dosing regimens for clinical reference. Through prediction of final model, the trough concentration was more likely < 5 mg/L when a routine dose of 10 mg/kg is administered every 6 h to 3-9-month-old infants. Therefore, the dose should be increased in the treatment of infant septicemia.

Conclusions: The stable and effective PopPK model of vancomycin in Chinese infants with septicemia was established. This model has satisfactory predictive ability for clinically individualized dosing regimens in this vulnerable population.
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http://dx.doi.org/10.1186/s40360-021-00489-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097779PMC
May 2021

PDGFR-β fibroblasts deteriorate survival in human solid tumors: a meta-analysis.

Aging (Albany NY) 2021 May 3;13. Epub 2021 May 3.

Department of General Surgery III, Affiliated Hospital of Shaoxing University, Zhejiang 312000, China.

Fibroblasts are a highly heterogeneous population in tumor microenvironment. PDGFR-β fibroblasts, a subpopulation of activated fibroblasts, have proven to correlate with cancer progression through multiple of mechanisms including inducing angiogenesis and immune evasion. However, the prognostic role of these cells in solid tumors is still not conclusive. Herein, we carried out a meta-analysis including 24 published studies with 6752 patients searched from PubMed, Embase and EBSCO to better comprehend the value of such subpopulation in prognosis prediction for solid tumors. We noted that elevated density of intratumoral PDGFR-β fibroblasts was remarkably associated with worse overall survival (OS) and disease-free survival (DFS) of patients. In subgroup analyses, the data showed that PDGFR-β fibroblast infiltration considerably decreased OS in non-small cell lung cancer (NSCLC), breast and pancreatic cancer, and reduced DFS in breast cancer. In addition, increased number of PDGFR-β fibroblasts appreciably correlated with advanced TNM stage of patients. In conclusion, PDGFR-β fibroblast infiltration deteriorates survival in human solid tumors especially in NSCLC, breast and pancreatic cancer. Hence, they may offer a practicable prognostic biomarker and a potential therapeutic strategy for these patients.
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http://dx.doi.org/10.18632/aging.202952DOI Listing
May 2021

α-CaCdP and β-CaCdP: Two Polymorphic Phosphide-Based Infrared Nonlinear Crystals with Distorted NLO-Active Tetrahedral Motifs Realizing Large Second Harmonic Generation Effects and Suitable Band Gaps.

Inorg Chem 2021 May 3. Epub 2021 May 3.

Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, P. R. China.

Two polymorphic phosphide-based infrared (IR) nonlinear optical (NLO) crystals, α-CaCdP and β-CaCdP, were obtained by combining alkaline-earth metals and d transition metals using metal flux and metal salt flux methods, respectively. The crystal structure of α-CaCdP is orthorhombic in the space group C2 (no. 36), while the structure of β-CaCdP is monoclinic in the space group C (no. 8). Both are two-dimensional layered structures that are composed of CdP tetrahedra layers via sharing vertices, which stack along the -axis and the -axis, respectively. The second harmonic generation (SHG) measurements manifest that α-CaCdP and β-CaCdP exhibit strong SHG intensities (1.41 and 3.28× that of AgGaS at a 2050 nm laser, respectively). Other optical measurements indicate that α-CaCdP and β-CaCdP have suitable band gaps (1.98 and 1.55 eV, respectively), high laser-induced damage thresholds (4.5 and 3.1× that of AgGaS at 1064 nm laser, respectively) and appropriate birefringence (0.12 and 0.20 at 2050 nm, respectively) in addition to covering wide infrared transparent regions. The research on α-CaCdP and β-CaCdP demonstrates that they are potential IR NLO candidates. Theoretical calculations uncover that their SHG effects are from distorted CdP tetrahedra, highlighting that tetrahedral motifs, including d transition metals, would be ideal NLO-active building blocks.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01052DOI Listing
May 2021

Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.

J Clin Invest 2021 May;131(9)

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.

Intestinal farnesoid X receptor (FXR) signaling is involved in the development of obesity, fatty liver disease, and type 2 diabetes. However, the role of intestinal FXR in atherosclerosis and its potential as a target for clinical treatment have not been explored. The serum levels of fibroblast growth factor 19 (FGF19), which is encoded by an FXR target gene, were much higher in patients with hypercholesterolemia than in control subjects and were positively related to circulating ceramide levels, indicating a link between intestinal FXR, ceramide metabolism, and atherosclerosis. Among ApoE-/- mice fed a high-cholesterol diet (HCD), intestinal FXR deficiency (in FxrΔIE ApoE-/- mice) or direct FXR inhibition (via treatment with the FXR antagonist glycoursodeoxycholic acid [GUDCA]) decreased atherosclerosis and reduced the levels of circulating ceramides and cholesterol. Sphingomyelin phosphodiesterase 3 (SMPD3), which is involved in ceramide synthesis in the intestine, was identified as an FXR target gene. SMPD3 overexpression or C16:0 ceramide supplementation eliminated the improvements in atherosclerosis in FxrΔIE ApoE-/- mice. Administration of GUDCA or GW4869, an SMPD3 inhibitor, elicited therapeutic effects on established atherosclerosis in ApoE-/- mice by decreasing circulating ceramide levels. This study identified an intestinal FXR/SMPD3 axis that is a potential target for atherosclerosis therapy.
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http://dx.doi.org/10.1172/JCI142865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087211PMC
May 2021

Design and 3D modeling investigation of a microfluidic electrode array for electrical impedance measurement of single yeast cells.

Electrophoresis 2021 May 2. Epub 2021 May 2.

Key Laboratory of MEMS of Ministry of Education, Southeast University, Sipailou 2, Nanjing, 210018, P. R. China.

High-resolution microscopic imaging may cause intensive image processing and potential impact of light irradiation on yeast replicative lifespan (RLS). Electrical impedance spectroscopy (EIS) could be alternatively used to perform high-throughput and label-free yeast RLS assays. Prior to fabricating EIS-integrated microfluidic devices for yeast RLS determination, systematic modeling and theoretical investigation are crucial for device design and optimization. Here, we report three-dimensional (3D) finite-element modeling and simulations of EIS measurement in a microfluidic single yeast in-situ impedance array (SYIIA), which is designed by patterning an electrode matrix underneath a cell-trapping array. SYIIA was instantiated and modeled as a 5×5 sensing array comprising 25 units for cell immobilization, culturing and time-lapse EIS recording. Simulations of yeast growing and budding in a sensing unit demonstrated that EIS signals enable the characterization of cell growth and daughter-cell dissections. In the 5×5 sensing array, simulation results indicated that when monitoring a target cell, daughter dissections in its surrounding traps may induce variations of the recorded EIS signals, which could cause mistakes in identifying target daughter-cell dissections. To eliminate the mis-identifications, electrode array pitch was optimized. Therefore, the results could conduct the design and optimization of microfluidic electrode-array-integrated devices for high-throughput and accurate yeast RLS assays. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/elps.202100028DOI Listing
May 2021

Construction and Application of MALDI-TOF Mass Spectrometry for the Detection of Haemophilus parasuis.

Biomed Res Int 2021 15;2021:5588855. Epub 2021 Apr 15.

Shanghai Animal Disease Control Center, 855 Hongjin Road, Shanghai 201103, China.

To construct a protein fingerprint database of (), thus improving its clinical diagnosis efficiency. A total of 15 standard strains were collected to establish a protein fingerprint database of using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and the effects of different culture media and culture time on the quality and identification results of the protein fingerprint were investigated. The results showed that tryptone soy agar (TSA) and tryptone soy broth (TSB) media and different incubation times had no significant effect on the characteristic peaks of the protein profiles. In addition, 18 clinical isolates were used to compare the identification results of the self-built protein fingerprint database, PCR detection, and basic database. Only one strain was identified in the original VITEK-MS system database, while the self-made protein fingerprint database of was 100% accurate for the detection of 18 clinical isolate strains. The protein fingerprint database of built by our laboratory is suitable for rapid clinical diagnosis of , due to its high accuracy, efficiency, and strong specificity.
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http://dx.doi.org/10.1155/2021/5588855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062181PMC
April 2021

Clinical Therapy of Metastatic Spinal Tumors.

Front Surg 2021 15;8:626873. Epub 2021 Apr 15.

Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China.

Metastatic spinal tumors (MST) have high rates of morbidity and mortality. MST can destroy the vertebral body or compress the nerve roots, resulting in an increased risk of pathological fractures and intractable pain. Here, we elaborately reviewed the currently available therapeutic options for MST according to the following four aspects: surgical management, minimally invasive therapy (MIT), radiation therapy, and systemic therapy. In particular, these aspects were classified and introduced to show their developmental process, clinical effects, advantages, and current limitations. Furthermore, with the improvement of treatment concepts and techniques, we discovered the prevalent trend toward the use of radiation therapy and MIT in clinic therapies. Finally, the future directions of these treatment options were discussed. We hoped that along with future advances and study will lead to the improvement of living standard and present status of treatment in patients with MST.
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http://dx.doi.org/10.3389/fsurg.2021.626873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084350PMC
April 2021

Circadian rhythm-associated Rev-erbα modulates polarization of decidual acrophage via PI3K/Akt signaling pathway.

Am J Reprod Immunol 2021 May 2:e13436. Epub 2021 May 2.

NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200090, China.

Problem: Circadian rhythms are involved not only in the repair and regeneration of the immune system, but may also be associated with regulation of inflammation and immune responses. Rev-erbα could constitute a link between immunity and circadian rhythms since it is a transcription factor that regulates circadian rhythms and has functions in multiple physiological and pathological processes. Decidual macrophages (dMφs) play crucial roles in immune balance at the maternal-fetal interface, and abnormal macrophage polarization is related to adverse pregnancy outcomes, such as infertility, recurrent spontaneous abortion and preterm labor. However, whether Rev-erbα could modulate the polarization of macrophages is unknown.

Methods Of Study: In this study, we analyzed the phenotype of dMφs and the expression of Rev-erbα in dMφs from normal pregnancies and miscarriages. The effect of Rev-erbα on macrophage polarization was evaluated by its knockdown or pharmacological activation. The mechanism by which the Rev-erbα agonist SR9009 regulates macrophage polarization was also estimated.

Results: A type-1 macrophage (M1)-like dominance was observed in dMφs from human miscarriages, with a decreased expression of Rev-erbα compared to that from normal pregnancies. Rev-erbα knockdown promoted M1 polarization in macrophages differentiated from THP1 cell line, whereas pharmacological activation of Rev-erbα by SR9009 induced type-2 macrophage (M2)-like polarization in dMφs. Furthermore, we found that SR9009 induced M2 polarization in macrophages differentiated from U937 cell line via the PI3K/Akt signaling pathway.

Conclusion: Rev-erbα may play an essential role in macrophage polarization. These findings might help elucidate the role of Rev-erbα in regulating the differentiation and functions of macrophages and suggest a therapeutic target for pregnancy loss and pregnancy complications.
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http://dx.doi.org/10.1111/aji.13436DOI Listing
May 2021

Magnetic resonance angiography and perfusion mapping by arterial spin labeling using Fourier transform-based velocity-selective pulse trains: Examination on a commercial perfusion phantom.

Magn Reson Med 2021 May 2. Epub 2021 May 2.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion-mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)-based velocity-selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom.

Methods: The FT velocity-selective saturation-based MRA and FT velocity-selective inversion-based ASL perfusion imaging were compared with time-of-flight and pseudo-continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity-selective MRA (VSMRA) and velocity-selective ASL (VSASL) were each performed with three velocity-encoding directions: foot-head, left-right, and oblique 45°. The contrast-to-noise ratio for MRA scans and perfusion-weighted signal, as well as labeling efficiency for ASL methods, were quantified.

Results: On this phantom with feeding tubes having only vertical and transverse flow directions, VSMRA and VSASL exhibited the dependence of velocity-encoding directions. The foot-head-encoded VSMRA and VSASL generated similar signal contrasts as time of flight and pseudo-continuous ASL for the two flow rates, respectively. The oblique 45°-encoded VSMRA yielded more uniform contrast-to-noise ratio across slices than foot-head and left-right-encoded VSMRA scans. The oblique 45°-encoded VSASL elevated labeling efficiency from 0.22-0.68 to 0.82-0.90 through more uniform labeling of the entire feeding tubes.

Conclusion: Both FT velocity-selective saturation-based VSMRA and FT velocity-selective inversion-based VSASL were characterized on a commercial perfusion phantom. Careful selection of velocity-encoding directions along the major vessels is recommended for their applications in various organs.
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http://dx.doi.org/10.1002/mrm.28805DOI Listing
May 2021

Facile in situ fabrication of ZnO-embedded cellulose nanocomposite films with antibacterial properties and enhanced mechanical strength via hydrogen bonding interactions.

Int J Biol Macromol 2021 Apr 28;183:760-771. Epub 2021 Apr 28.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100083, PR China; Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, PR China. Electronic address:

Nano-ZnO were in situ prepared and permanently embedded in regenerated cellulose (RC) films by chemical precipitation to endow antibacterial of films and simultaneously strengthen tensile strength. ZnCl was selected as a promoter of 1-allyl-3-methylimidazolium chloride for cellulose dissolution and as a precursor for nano-ZnO synthesis. Zn-absorbed cellulose solution was reacted with NaOH under ultrasonic to obtain nano-ZnO embedded RC films. The results indicated that RC films treated with the longest sonication time, highest regeneration solution basicity, and highest cellulose concentration were demonstrated to be the most effective against S. aureus, which agreed well with the dense and homogeneous distribution of high content of nano-ZnO on the film surface. The nanocomposite films achieved particularly high mechanical strength of 202.0 MPa with improved thermal stability. Strong H-bonding formed between nano-ZnO and cellulose, which contributed to high tensile strength and thermal stability of films. This work affords a simple approach to prepare cellulose nanocomposite with outstanding performance for potential application in packaging.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.175DOI Listing
April 2021

First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Oncol 2021 13;11:598265. Epub 2021 Apr 13.

Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China.

Objective: The aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.

Methods: A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.

Results: A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50-0.64; P <0.00001) and 0.70 (95% CI = 0.54-0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10-1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.

Conclusions: Compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.
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http://dx.doi.org/10.3389/fonc.2021.598265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076535PMC
April 2021

Cancer Physical Hallmarks as New Targets for Improved Immunotherapy.

Trends Cell Biol 2021 Apr 26. Epub 2021 Apr 26.

Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, P.R. China; MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R. China. Electronic address:

A low response rate is the major challenge for existing cancer immunotherapies. Physical cues in the tumor microenvironment (TME) have been recognized as new hallmarks of cancer, which may synergistically contribute to low immunotherapy response. Recent evidence indicates that the physical hallmarks of cancer hold great potential as new targets for improved immunotherapy.
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http://dx.doi.org/10.1016/j.tcb.2021.03.011DOI Listing
April 2021

FATP4 inactivation in cultured macrophages attenuates M1- and ER stress-induced cytokine release via a metabolic shift towards triacylglycerides.

Biochem J 2021 Apr 26. Epub 2021 Apr 26.

University of Heidelberg Hospital, Heidelberg, Germany.

Fatty acid transport protein 4 (FATP4) belongs to a family of acyl-CoA synthetases which activate long-chain fatty acids into acyl-CoAs subsequently used in specific metabolic pathways. Patients with FATP4 mutations and Fatp4-null mice show thick desquamating skin and other complications, however, FATP4 role on macrophage functions has not been studied. We here determined whether the levels of macrophage glycerophospholipids, sphingolipids including ceramides, triacylglycerides, and cytokine release could be altered by FATP4 inactivation. Two in vitro experimental systems were studied: FATP4-knockdown in THP-1-derived macrophages undergoing M1 (LPS+IFNγ) or M2 (IL-4) activation and bone marrow-derived macrophages (BMDMs) from macrophage-specific Fatp4-knockout (Fatp4M-/-) mice undergoing tunicamycin (TM)-induced ER stress. FATP4-deficient macrophages showed a metabolic shift towards triacylglycerides and were protected from M1- or TM-induced release of pro-inflammatory cytokines and cellular injury. Fatp4M-/- BMDMs showed specificity in attenuating TM-induced activation of inositol-requiring enzyme1α, but not other unfolded protein response pathways. Under basal conditions, FATP4/Fatp4 deficiency decreased the levels of ceramides and induced an upregulation of mannose receptor CD206 expression. The deficiency led to an attenuation of IL-8 release in THP-1 cells as well as TNF-α and IL-12 release in BMDMs. Thus, FATP4 functions as an acyl-CoA synthetase in macrophages and its inactivation suppresses the release of pro-inflammatory cytokines by shifting fatty acids towards the synthesis of specific lipids.
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http://dx.doi.org/10.1042/BCJ20210155DOI Listing
April 2021

A fast and ultrasensitive ELISA based on rolling circle amplification.

Analyst 2021 May 26;146(9):2871-2877. Epub 2021 Apr 26.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R. China. and Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, P.R. China.

A highly sensitive ELISA is critical for early diagnosis and biomarker discovery of various diseases. Although various ELISA technologies have been developed with high sensitivity, they are limited by poor repeatability, high cost, the dependence on complex equipment and/or a prolonged reaction time. To this end, we developed a fast and ultrasensitive ELISA (termed RELISA) based on rolling circle amplification (RCA) and enzymatic signal amplification. The RELISA is established on the traditional ELISA, with only one more RCA step that can be accomplished within 10 minutes. The prolonged single strand DNA (ssDNA) from RCA is able to enrich abundant horseradish peroxidase conjugate (HRP) modified detection probes. Consequently, the intensive HRP is able to catalyze TMB-HO to produce significantly enhanced colorimetric signals. With CEACAM-7 as a model biomarker, the RELISA achieves the limit of detection as low as 2.82 pg mL, which is ∼50 times higher than that of the traditional ELISA. Therefore, we envision that the developed RELISA would be a powerful tool for the early diagnosis of various major diseases.
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http://dx.doi.org/10.1039/d1an00355kDOI Listing
May 2021

Sensitivities of Ozone Air Pollution in the Beijing-Tianjin-Hebei Area to Local and Upwind Precursor Emissions Using Adjoint Modeling.

Environ Sci Technol 2021 05 23;55(9):5752-5762. Epub 2021 Apr 23.

Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado 80309, United States.

Effective mitigation of surface ozone pollution entails detailed knowledge of the contributing precursors' sources. We use the GEOS-Chem adjoint model to analyze the precursors contributing to surface ozone in the Beijing-Tianjin-Hebei area (BTH) of China on days of different ozone pollution severities in June 2019. We find that BTH ozone on heavily polluted days is sensitive to local emissions, as well as to precursors emitted from the provinces south of BTH (Shandong, Henan, and Jiangsu, collectively the SHJ area). Heavy ozone pollution in BTH can be mitigated effectively by reducing NO (from industrial processes and transportation), ≥C alkenes (from on-road gasoline vehicles and industrial processes), and xylenes (from paint use) emitted from both BTH and SHJ, as well as by reducing CO (from industrial processes, transportation, and power generation) and ≥C alkanes (from industrial processes, paint and solvent use, and on-road gasoline vehicles) emissions from SHJ. In addition, reduction of NO, xylene, and ≥C alkene emissions within BTH would effectively decrease the number of BTH ozone-exceedance days. Our analysis pinpoint the key areas and activities for locally and regionally coordinated emission control efforts to improve surface ozone air quality in BTH.
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http://dx.doi.org/10.1021/acs.est.1c00131DOI Listing
May 2021

Concomitant mutation status of -rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib.

Transl Lung Cancer Res 2021 Mar;10(3):1525-1535

Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin, China.

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase () rearrangement characterizes a subgroup of patients who show sensitivity to tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients.

Methods: We retrospectively analyzed 96 patients with NSCLC with detected by immunohistochemical staining (VENTANA anti-(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed.

Results: Among the 96 patients with immunohistochemically identified fusions, 80 (83%) were confirmed by next-generation sequencing. mutation was the most commonly co-occurring mutation with rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog () G12, 1 epidermal growth factor receptor () 19del, and 1 exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 ()- fusions were identified in 95% of -rearranged patients, with 16.2% of them also harboring additional non-- fusions. Nineteen non- translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring alterations showed a trend toward shorter progression-free survival (6 13 months, P=0.064) and significantly shorter overall survival (11 32 months, P=0.004) than did -wild-type patients. Patients with concomitant alterations in the signaling pathway also had a shorter median overall survival than those without such alterations (23 32 months, P=0.014), whereas progression-free survival did not differ significantly.

Conclusions: The spectrum of -fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of -rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy.
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http://dx.doi.org/10.21037/tlcr-21-160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044492PMC
March 2021

Paeoniflorin suppresses allergic and inflammatory responses by promoting autophagy in rats with urticaria.

Exp Ther Med 2021 Jun 8;21(6):590. Epub 2021 Apr 8.

Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.

Paeoniflorin (PF) has been reported to be effective against several skin disorders, such as allergic contact dermatitis and psoriasis; however, it remains unclear whether PF can protect against urticarial lesions. Herein, the effects of PF on rats with urticarial lesions and the possible underlying mechanism were investigated. The effects of PF administration on a rat model of ovalbumin-induced urticarial-like lesions were evaluated via pathological analysis using hematoxylin-eosin staining. Toluidine blue staining was performed to detect mast cells and ELISA was performed to determine serum histamine levels. PF-induced regulatory effects on autophagic activity and the potential underlying mechanism of this were also investigated using transmission electron microscopy, immunohistochemistry and reverse transcription-quantitative PCR. It was demonstrated that PF suppressed allergic and inflammatory responses to improve urticarial lesions, as evidenced by the attenuation of pathological abnormalities, mast cell infiltration and histamine secretion. Mechanistically, PF treatment was found to markedly limit the production and release of inflammatory cytokine interleukin (IL)-23, while the levels of IL-17 remained unchanged. PF intervention led to an increased number of autophagosomes, along with higher levels of light chain 3B (LC3B) and Beclin-1, and lower levels of P62, indicating that PF could augment autophagic activity in urticarial lesions. PF treatment increased the expression of liver kinase B1 (LKB1) and AMP-activated protein kinase-α (AMPK-α), contributing to the PF-enhanced autophagic activity. In conclusion, PF could effectively improve urticarial lesions by inhibiting inflammatory cytokine IL-23 and increasing the autophagic activity via the LKB1/AMPK-α pathway.
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http://dx.doi.org/10.3892/etm.2021.10022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056118PMC
June 2021