Publications by authors named "Yan Fan"

287 Publications

of Promotes Lateral Root Proliferation and Sensitizes to Salt Stress.

Front Plant Sci 2021 4;12:669143. Epub 2021 Jun 4.

College of Forestry, Shanxi Agricultural University, Jinzhong, China.

The aggravation of soil salinization limits the growth and development of plants. The AP2/ERF transcription factors (TFs) have been identified and play essential roles in plant development and stress response processes. In this study, the function of was detected using the overexpressing (OX) and RNAi transgenic poplar 84K hybrids. Plant growth, stomatal conductance, antioxidant enzymes activity, and co-expressed were analyzed using morphological, physiological, and molecular methods. OX showed a more robust lateral root system with a bigger diameter and volume compared to the wild-type plants (WT). Physiological parameters indicated the bigger stomatal aperture and lower stomatal density of OX along with the lower Catalase (CAT) activity and higher malondialdehyde (MDA) content contributed to the salt sensitivity. The plant height and rooting rate of OX and RNAi were significantly worse compared to WT. Other than that, the morphology and physiology of RNAi plants were similar to WTs, suggesting that the function of may be redundant with other TFs. Our results indicate that when expression is either too high or too low, poplar growth and rooting is negatively affected. In addition, a downstream target TF, NAC45, involved in Auxin biosynthesis, was identified and could directly bind to its promoter to negatively regulate its expression. These results shed new light on the function of ERF TFs in plant root growth and salt stress tolerance.
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http://dx.doi.org/10.3389/fpls.2021.669143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213033PMC
June 2021

CUL4 lung adenocarcinomas are dependent on the CUL4-p21 ubiquitin signaling for proliferation and survival.

Am J Pathol 2021 Jun 10. Epub 2021 Jun 10.

Department of Pathology and Laboratory Medicine, The Joan and Stanford I. Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address:

Cullin 4A and 4B ubiquitin ligases are often highly accumulated in human malignancies, and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. In this study, we report that both CUL4A and CUL4B are highly expressed in non-small cell lung cancer (NSCLC) patients, and high expression of both is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4A) or CUL4B (CUL4B) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells both in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLC. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells upon CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4A or CUL4B NSCLC cells and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4A CUL4B may serve as a prognostic marker and therapeutic target for NSCLC patients.
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http://dx.doi.org/10.1016/j.ajpath.2021.05.018DOI Listing
June 2021

DINs: Deep Interactive Networks for Neurofibroma Segmentation in Neurofibromatosis Type 1 on Whole-Body MRI.

IEEE J Biomed Health Inform 2021 Jun 9;PP. Epub 2021 Jun 9.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that involves the central and peripheral nervous systems. Accurate detection and segmentation of neurofibromas are essential for assessing tumor burden and longitudinal tumor size changes. Automatic convolutional neural networks (CNNs) are sensitive and vulnerable as tumors' variable anatomical location and heterogeneous appearance on MRI. In this study, we propose deep interactive networks (DINs) to address the above limitations. User interactions guide the model to recognize complicated tumors and quickly adapt to heterogeneous tumors. We introduce a simple but effective Exponential Distance Transform (ExpDT) that converts user interactions into guide maps regarded as the spatial and appearance prior. Comparing with popular Euclidean and geodesic distances, ExpDT is more robust to various image sizes, which reserves the distribution of interactive inputs. Furthermore, to enhance the tumor-related features, we design a deep interactive module to propagate the guides into deeper layers. We train and evaluate DINs on three MRI data sets from NF1 patients. The experiment results yield significant improvements of 44% and 14% in DSC comparing with automated and other interactive methods, respectively. We also experimentally demonstrate the efficiency of DINs in reducing user burden when comparing with conventional interactive methods.
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http://dx.doi.org/10.1109/JBHI.2021.3087735DOI Listing
June 2021

Having to Work from Home: Basic Needs, Well-Being, and Motivation.

Int J Environ Res Public Health 2021 05 13;18(10). Epub 2021 May 13.

Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.

During the COVID-19 pandemic, many employees were asked to start working from home for an extended time. The current study investigated how well employees worked and felt in this novel situation by following = 199 German employees-56% of them female, 24% with childcare duties-over the course of two working weeks in which they reported once daily on their well-being (PANAS-20, detachment) and motivation (work engagement, flow). Participants reported on organizational and personal resources (emotional exhaustion, emotion regulation, segmentation preference, role clarity, job control, social support). Importantly, they indicated how well their work-related basic needs, i.e., autonomy, competence, and relatedness, were met when working from home and how these needs had been met in the office. Multilevel models of growth showed that work engagement, flow, affect and detachment were on average positive and improving over the two weeks in study. Higher competence need satisfaction predicted better daily work engagement, flow, and affect. In a network model, we explored associations and dynamics between daily variables. Overall, the results suggest that people adapted well to the novel situation, with their motivation and well-being indicators showing adequate levels and increasing trajectories. Avenues for improving work from home are job control and social support.
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http://dx.doi.org/10.3390/ijerph18105149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152264PMC
May 2021

Discovery of a new class of JMJD6 inhibitors and structure-activity relationship study.

Bioorg Med Chem Lett 2021 Jul 13;44:128109. Epub 2021 May 13.

Department of Medicinal Chemistry, School of Medicine, Nankai University, Tianjin 300071, PR China. Electronic address:

JmjC domain-containing protein 6 (JMJD6) has been thought as a potential target for various diseases particularly cancer. However, few selective JMJD6 inhibitors have been reported. In this investigation, molecular docking and biological activity evaluation were performed to retrieve new JMJD6 inhibitors, which led to the identification of a hit compound, J2. Further structural optimization and structure-activity relationship (SAR) analysis towards J2 were carried out, which gave a new potent JMJD6 inhibitor, 7p. This compound showed an IC value of 0.681 μM against JMJD6, but displayed no activity against other tested JmjC domain-containing protein family members, indicating good selectivity (>100 fold). Collectively, this investigation offers a selective JMJD6 inhibitor, which could be taken as a lead compound for subsequent drug discovery targeting JMJD6.
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http://dx.doi.org/10.1016/j.bmcl.2021.128109DOI Listing
July 2021

Preparation of metal organic framework derived materials [email protected] and its application for degradation of norfloxacin from aqueous solutions by activated peroxymonosulfate.

Chemosphere 2021 Jul 24;275:130059. Epub 2021 Feb 24.

College of Environmental & Energy Engineering, Beijing University of Technology, Beijing, 100124, PR China.

The metal organic framework derived materials ([email protected]) activated peroxymonosulfate (PMS) to degrade Norfloxacin (NOR) owing to the characteristics of high surface area (109.658 m g) and abundant mesoporous structure. The characterization results demonstrated that the optimal ratio of bimetal and of bimetallic to organic ligands (M/O) had good crystal structure and stability (Fe/Co = 3:1, M/O = 2:1). Moreover, NOR (10 mg L) removal of 98.78% was achievable in 60 min with an optimum concentration of PMS (0.32 mM) and dosage of [email protected] (0.1 g L). The radical quenching results suggested that SO·, ·OH and O functioned in the presence of the system certificated by XPS spectra. The presence of Cl and CO/HCO promoted the catalyst reaction. The recoverability revealed high removal efficiency of NOR of 93.55% could still be maintained. Furthermore, four pathways of NOR degradation were proposed, including dehydroxylation, defluorination, quinolone group conversion and piperazine ring transformation, which were attributed to the synergy of reactive oxygen species. The above results highlight that the method is of great significance to the practical application of heterogeneous catalysts in aqueous solutions.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130059DOI Listing
July 2021

Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[F]FDG PET/CT.

Eur J Nucl Med Mol Imaging 2021 May 12. Epub 2021 May 12.

Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China.

Purpose: Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC).

Methods: Ninety patients with newly diagnosed ccRCC who underwent 2-[F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy.

Results: Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value.

Conclusions: Our findings demonstrated that 2-[F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.
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http://dx.doi.org/10.1007/s00259-021-05399-9DOI Listing
May 2021

Restoration of Noradrenergic Function in Parkinson's Disease Model Mice.

ASN Neuro 2021 Jan-Dec;13:17590914211009730

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, United States.

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson's disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.
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http://dx.doi.org/10.1177/17590914211009730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114769PMC
May 2021

Impact of simethicone on bowel cleansing during colonoscopy in Chinese patients.

World J Clin Cases 2021 Apr;9(10):2238-2246

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China.

Background: Four-liter polyethylene glycol (PEG) solutions are effective for bowel cleansing, but their large volume might hinder patient compliance. Due to the unique features of Asians, 4 L PEG might be a suboptimal bowel preparation in predominantly ethnically Asian countries. In view of this, a balance should be achieved between the volume and effectiveness. The ideal bowel cleansing regimen for a colonoscopy has yet to be determined in a Chinese population.

Aim: To compare the cleansing efficacy of 3 L PEG plus simethicone with 4 L PEG.

Methods: A total of 291 patients were randomly allocated to two groups: Group 1 ( = 145) received 4 L split-dose PEG (4-P); group 2 ( = 146) received 3 L split-dose PEG plus simethicone (3-PS). Bowel-cleansing efficacy was evaluated by endoscopists using the Boston bowel preparation scale (BBPS) and the bubbles score.

Results: Although there were no significant differences in the total BBPS score or the adequate rate of bowel preparation between the two groups, the BBPS score of the right-side colon was significantly higher in the 3-SP group (2.37 ± 0.54 2.21 ± 0.78; = 0.04). Moreover, the use of simethicone significantly reduced bubbles in all colon segments ( < 0.001). The mean withdrawal time was significantly shorter in the 3-PS group (8.8 ± 3.4 9.6 ± 2.3; = 0.02). Furthermore, significantly more proximal adenomas were detected in the 3-PS group (53.6% 45.7%; = 0.03). In addition, the proportions of patients with nausea and bloating were significantly lower in the 3-SP group ( < 0.01 for both). More patients in the 3-PS group expressed willingness to repeat the bowel preparation (87.7% 76.6%, = 0.01).

Conclusion: Three-liter PEG shows satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone with better bubble elimination and enhanced patient acceptance offers excellent potential impact on the detection of proximal adenomas in Chinese patients.
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http://dx.doi.org/10.12998/wjcc.v9.i10.2238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026841PMC
April 2021

Deoxymikanolide adversely altered physiology and ultrastructure of Ralstonia solanacearum.

Pestic Biochem Physiol 2021 May 24;174:104803. Epub 2021 Feb 24.

Department of Pesticides, Key Laboratory of Pesticide Chemistry and Application, State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

Deoxymikanolide (DEO) was isolated from Mikania micrantha Bunge and identified as a novel antibacterial compound previously. However, the mode of antimicrobial mechanism of DEO was not clear but hypothesized to affect the morphology and physiology of Ralstonia solanacearum cells. In this study, we confirmed our hypothesis via transmission electron microscopy (TEM) observation and comprehensive physiological analyses, including electric conductivity, glycan and phosphorus metabolism, activities of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), intrabacterial reactive oxygen species (ROS), and malondialdehyde (MDA) levels. We found that glycan and phosphorus metabolism, electric conductivity, intracellular ROS and MDA levels of R. solanacearum cells were significantly increased, while the activities of three antioxidant enzymes were significantly inhibited by DEO treatment. Moreover, TEM analysis showed that DEO treatment led to an early-stage of cell shrinkage, intermediate-stages of cytoplasmic damage, and a final-stage of cell disruption. Altogether, our data presented here indicate that DEO could adversely affect the physiology and morphology of R. solanacearum cells and be treated as an alternative antibacterial treatment in the future.
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http://dx.doi.org/10.1016/j.pestbp.2021.104803DOI Listing
May 2021

Epigenetic transcripts of LINC01311 and hsa-miR-146a-5p regulate neural development in a cellular model of Alzheimer's disease.

IUBMB Life 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurology, Liaocheng People's Hospital, Liaocheng City, Shandong Province, China.

Emerging evidence has shown that Long noncoding RNAs (LncRNAs) are aberrantly expressed and functionally involved in the development of neurodegenerative disorders. In this work, we investigated the regulatory effects of lncRNA of LINC01311 and its competing endogenous RNA target of hsa-miR-146a-5p in a cellular model of Alzheimer's disease (AD). SH-SY5Y cells were treated with synthetic Βeta-Amyloid Peptide (1-42) (AB1-42) in vitro to induce AD-like neural injuries. Expressions of LINC01311 and hsa-miR-146a-5p were monitored by qRT-PCR. LINC01311 was upregulated and hsa-miR-146a-5p downregulated to examine their functional regulations on AB1-42-induced apoptosis, proliferation slowdown, autophagy, and amyloid precursor protein (APP) accumulations. Hsa-miR-146a-5p was also overexpressed in LINC01311-upregulated SH-SY5Y cells to examine their correlated regulations on AB1-42-induced neural injuries. LINC01311 was downregulated whereas hsa-miR-146a-5p upregulated in AB1-42 treated SH-SY5Y cells. LINC01311 upregulation and hsa-miR-146a-5p downregulation protected AB1-42-induced apoptosis, proliferation slowdown, autophagy, and APP accumulations in SH-SY5Y cells. Hsa-miR-146a-5p overexpression reversed the protection of LINC01311 on AB1-42-induced neural injuries. Our work demonstrated that the epigenetic axis of LINC01311/hsa-miR-146a-5p was involved in the functional regulation of human-lineage neurons in a cellular model of AD, thus suggesting a clinical potential of exploring epigenetic network for treating AD patients.
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http://dx.doi.org/10.1002/iub.2472DOI Listing
April 2021

Crystal structures of two inhibitors in complex with histone lysine demethylase 4D (KDM4D) provide new insights for rational drug design.

Biochem Biophys Res Commun 2021 05 27;554:71-75. Epub 2021 Mar 27.

Department of Medicinal Chemistry, School of Medicine, Nankai University, Tianjin, 300071, PR China. Electronic address:

Histone lysine demethylase 4D (KDM4D), also known as JMJD2D, plays an important role in cell proliferation and survival and has been associated with several tumor types. KDM4D has emerged as a potential target for the treatment of human cancer. Here, we reported crystal complex structures for two KDM4D inhibitors, OWS [2-(1H-pyrazol-3-yl)isonicotinic acid] and 10r (5-hydroxy-2-methylpyrazolo[1,5-a]pyrido[3,2-e]pyrimidine-3-carbonitrile), which were both determined to 2.0 Å. OWS is a newly discovered KDM4D inhibitor (IC = 4.28 μM) and the critical pharmacophores of this compound are confirmed by the complex structure. Compound 10r is a KDM4D inhibitor reported by us previously. To clarify the binding mode in more detail, the crystal structure was determined and the comparison analysis revealed unique interactions that had never been observed before. Overall, our data provide new structural insights for rational design and offer an opportunity for optimization of KDM4D inhibitors.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.083DOI Listing
May 2021

Paeoniflorin reduces the inflammatory response of THP-1 cells by up-regulating microRNA-124 : Paeoniflorin reduces the inflammatory response of THP-1 cells through microRNA-124.

Genes Genomics 2021 Jun 29;43(6):623-631. Epub 2021 Mar 29.

Dermatology, Hangzhou Traditional Chinese Medicine Hospital, Dingqiao Campus, Hangzhou, 310006, Zhejiang, China.

Background: The activation of macrophages and the release of inflammatory cytokines are the main reasons for the progress of systemic lupus erythematosus (SLE). MicroRNA (miRNA)-124 is involved in the regulation of macrophages and is a key regulator of inflammation and immunity.

Objective: To explore whether paeoniflorin (PF) regulates the biological functions of macrophages depends on miR-124.

Methods: RT-PCR, WB, ELISA, CCK-8 and flow cytometry were used to evaluate that PF regulated the biological functions of THP-1 cells through miR-124.

Results: PF significantly inhibited the proliferation while promotes the apoptosis of THP-1 cells, and inhibited the release of IL-6, TNF-α and IL-1βin THP-1 cells. RT-PCR results shown that PF up-regulated the expression of miR-124 in THP-1 cells. Functional recovery experiments showed that compared with the LPS + mimic-NC group, LPS + miR-124 mimic significantly inhibited the proliferation and the release of IL-6, TNF-α and IL-1β, but promoted the apoptosis of THP-1 cells. In addition, compared with the LPS + PF + inhibitor-NC group, LPS + PF + miR-124 inhibitor significantly promoted the proliferation and the release of IL-6, TNF-α and IL-1β, but inhibited the apoptosis of THP-1 cells.

Conclusions: By down-regulating miR-124, PF inhibits the proliferation and inflammation of THP-1 cells, and promotes the apoptosis of THP-1 cells.
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http://dx.doi.org/10.1007/s13258-021-01083-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131308PMC
June 2021

Mechanistic insights into the adsorption and bioactivity of fibronectin on surfaces with varying chemistries by a combination of experimental strategies and molecular simulations.

Bioact Mater 2021 Oct 9;6(10):3125-3135. Epub 2021 Mar 9.

Key Laboratory of Biomedical Engineering of Guangdong Province, Guangzhou, 510006, China.

Fibronectin (Fn) is significant to the performance of biomaterials, and the chemistry of biomaterial surface play important roles in Fn adsorption and subsequent cell behavior. However, the "molecular scale" mechanism is still unclear. Herein, we combined experimental strategies with molecular simulations to solve this problem. We prepared self-assembled monolayers with varying chemistries, i.e., SAMs-CH, SAMs-NH, SAMs-COOH and SAMs-OH, and characterized Fn adsorption and cell behaviors on them. Next, Monte Carlo method and all-atom molecular dynamics simulations were employed to reveal the orientation/conformation of Fn on surfaces. We found that SAMs-CH strongly adsorbed Fn via hydrophobic interactions, but show poor bioactivity as the low exposure of RGD/PHSRN motifs and the deformation of Fn. SAMs-NH and SAMs-COOH could adsorb Fn efficiently via vdW interactions, electrostatic interactions, hydrogen bonds and salt bridges. Fn exhibited excellent bioactivity for cell adhesion, proliferation and osteogenic differentiation as high exposure of bioactive motifs on SAMs-NH, or as the activation of other inferior cell-binding motifs on SAMs-COOH. SAMs-OH showed poor Fn adsorption as the water film. However, the adsorbed Fn displayed non-negligible bioactivity due to high exposure of PHSRN motif and large degree of protein flexibility. We believe that the revealed mechanism presents great potential to rationally design Fn-activating biomaterials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960943PMC
October 2021

Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.

Antioxid Redox Signal 2021 Apr 29. Epub 2021 Apr 29.

Department of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA.

Cellular response to hypoxia can include transition from respiration to glycolysis upregulation of glycolytic enzymes and transporters, as well as mitophagy induction to eliminate surplus mitochondria. Our purpose was to evaluate the impact of hypoxia-inducible factor-1α (HIF-1α) stabilization on mitochondrial homeostasis and oxidative stress in a chronic model of glaucoma. Retina and optic nerve (ON) were evaluated from young and aged DBA/2J (D2) glaucoma model mice and the control strain, the DBA/2-. Hypoxic retinal ganglion cells (RGCs) were observed in young and aged D2 retina, with a significant increase in HIF-1α protein in the aged D2 retina. Reactive oxygen species observed in young D2 retina and ON were followed by significant decreases in antioxidant capacity in aged D2 retina and ON. HIF-1α targets such as neuron-specific glucose transporter-3 and lactate dehydrogenase were decreased or unchanged, respectively, in aged D2 retina despite an increased hypoxia response in RGCs. Mitochondrial mass was decreased in aged D2 retina concomitant with decreased mitochondrially encoded electron transport chain transcripts despite a stable nuclear-encoded TFAM (mitochondrial transcription factor), suggesting a breakdown in the nuclear-mitochondrial communication. Decreased mitophagy-associated proteins p62 and Rheb were observed in aged D2 retina, although p62 was significantly increased in the aged D2 ON. The increased reactive oxygen species concomitant with HIF-1α upregulation despite reduced glucose transporters, mis-match of nuclear- and mitochondrial-encoded transcripts, and signs of reduced mitophagy suggest that retinas from D2 mice with chronic intraocular pressure elevation transition to pseudohypoxia without consistent metabolic reprogramming before significant RGC loss.
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http://dx.doi.org/10.1089/ars.2020.8180DOI Listing
April 2021

Identifying the Manipulation of Individual Atomic-Scale Defects for Boosting Thermoelectric Performances in Artificially Controlled BiTe Films.

ACS Nano 2021 Mar 8;15(3):5706-5714. Epub 2021 Mar 8.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

The manipulation of individual intrinsic point defects is crucial for boosting the thermoelectric performances of n-BiTe-based thermoelectric films, but was not achieved in previous studies. In this work, we realize the independent manipulation of Te vacancies V and antisite defects of Te and Bi in molecular beam epitaxially grown n-BiTe films, which is directly monitored by a scanning tunneling microscope. By virtue of introducing dominant Te antisites, the n-BiTe film can achieve the state-of-the-art thermoelectric power factor of 5.05 mW m K, significantly superior to films containing V and Bi as dominant defects. Angle-resolved photoemission spectroscopy and systematic transport studies have revealed two detrimental effects regarding V and Bi, which have not been discovered before: (1) The presence of Bi antisites leads to a reduction of the carrier effective mass in the conduction band; and (2) the intrinsic transformation of V to Bi during the film growth results in a built-in electric field along the film thickness direction and thus is not beneficial for the carrier mobility. This research is instructive for further engineering defects and optimizing electronic transport properties of n-BiTe and other technologically important thermoelectric materials.
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http://dx.doi.org/10.1021/acsnano.1c01039DOI Listing
March 2021

Combined Transcriptomic and Metabolomic Analysis Reveals the Role of Phenylpropanoid Biosynthesis Pathway in the Salt Tolerance Process of .

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

College of Plant Science, Jilin University, Xi'an Road, 5333 Changchun City, China.

Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on . We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.
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http://dx.doi.org/10.3390/ijms22052399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957753PMC
February 2021

Design, synthesis and biological assessment of novel CDK4 inhibitor with potent anticancer activity.

Bioorg Chem 2021 Apr 8;109:104717. Epub 2021 Feb 8.

Department of Medicinal Chemistry, School of Medicine, Nankai University, 94 Weijin Road, Tianjin, China. Electronic address:

Efforts toward finding potent CDK4 inhibitor for cancer therapy, a series of fluorine substituted pyrrolo[2,3-d]pyrimidine derivatives were designed, synthesized, and evaluated. Among them, the optimal lead compound 18i was discovered with potent activity against CDK4 at the nanomolar level (IC = 2.5 nM) and exquisite selectivity which demonstrated only modest activity against 3 out of the 394 protein kinases. 18i exhibited a much greater in vitro antiproliferative activity against several human cancer cell lines than that of the approved drug ribociclib. Further mechanism studies revealed that 18i effectively stimulated cancer cell cycle arrest in G phase and induced tumor cell apoptosis. In the comparison of in vivo therapeutic effects in xenograft mouse models of breast cancer, oral administration of 18i showed a significantly better degree of inhibitory effect to ribociclib without obvious toxicity. All of the results indicated that 18i could be a promising CDK4 inhibitor for treating malignancies.
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http://dx.doi.org/10.1016/j.bioorg.2021.104717DOI Listing
April 2021

Novel Functional Recombinant Human Follicle-Stimulating Hormone Acquired from Goat Milk.

J Agric Food Chem 2021 Mar 1;69(9):2793-2804. Epub 2021 Mar 1.

College of Animal Science and Technology, Northwest A&F University, Yangling 712100, P. R. China.

An animal mammary bioreactor is regarded as an excellent biological system which is applied to produce large-scale recombinant proteins in milk. However, there are no effective methods to produce a large amount of some pharmaceutical proteins, such as human follicle-stimulating hormone (FSH), by large animal mammary gland bioreactors due to the fact that accumulation of excessive bioactive FSH might cause serious diseases in animals. Here, we report a novel strategy of preparing recombinant human FSH (rhFSH) from goat mammary glands, which could avoid the accumulation of bioactive FSH in goats. First, the single inactive FSHα and FSHβ subunits expressed in goat mammary epithelial cells and goat mammary glands were performed to reassemble and were found to self-assemble into a complete heterodimer rhFSH at 4 °C and pH 7.4. Further, a cyclic adenosine monophosphate (cAMP) induction assay showed that the cAMP levels in cell lysate of HEK 293/FSHR cells were increased by about 8-fold in reassembled rhFSH groups than that in the control group ( < 0.01). Pharmacokinetic analysis indicated that the reassembled rhFSH from goat mammary glands was comparable to that of the commercially available Gonal-F ( > 0.05). In addition, the increasing dose of reassembled rhFSH significantly promoted ovulation of mouse and ovary weight gain of Sprague Dawley rat compared with the control groups and maximum values were up to 3-fold ( < 0.01) and 2.8-fold ( < 0.01), respectively. The reassembled rhFSH showed a similar effect to Gonal-F in inducing expression of FSH target genes and activating the PI3K pathway in granulosa cells. Our study developed a novel method to produce rhFSH and provided the basis for preparing FSH by the goat mammary gland bioreactor with less health problems on the producing animals.
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http://dx.doi.org/10.1021/acs.jafc.0c07208DOI Listing
March 2021

Windblown Sand-Induced Degradation of Glass Panels in Curtain Walls.

Materials (Basel) 2021 Jan 28;14(3). Epub 2021 Jan 28.

China Academy of Building Research, Beijing 100000, China.

The windblown sand-induced degradation of glass panels influences the serviceability and safety of these panels. In this study, the degradation of glass panels subject to windblown sand with different impact velocities and impact angles was studied based on a sandblasting test simulating a sandstorm. After the glass panels were degraded by windblown sand, the surface morphology of the damaged glass panels was observed using scanning electron microscopy, and three damage modes were found: a cutting mode, smash mode, and plastic deformation mode. The mass loss, visible light transmittance, and effective area ratio values of the glass samples were then measured to evaluate the effects of the windblown sand on the panels. The results indicate that, at high abrasive feed rates, the relative mass loss of the glass samples decreases initially and then remains steady with increases in impact time, whereas it increases first and then decreases with an increase in impact angle such as that for ductile materials. Both visible light transmittance and effective area ratio decrease with increases in the impact time and velocities. There exists a positive linear relationship between the visible light transmittance and effective area ratio.
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http://dx.doi.org/10.3390/ma14030607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866023PMC
January 2021

The risk factors for cognitive dysfunction in elderly patients after laparoscopic surgery: A retrospective analysis.

Medicine (Baltimore) 2021 Jan;100(2):e23977

Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital of Sichuan University, China.

Abstract: Postoperative cognitive dysfunction (POCD) is very common in clinical settings, it is necessary to analyze the risk factors for POCD in elderly patients after laparoscopic surgery to provide insights into clinical surgery management.Elderly patients undergone laparoscopy between September 1, 2018 and March 31, 2020 were included. The mini-mental state examination (MMSE) scale was used to evaluate the POCD, and the characteristics and clinical data of patients with and without POCD were collected and compared. Logistic regression was used to analyze the potential influencing factors.A total of 572 patients with laparoscopic surgery were included. The incidence of POCD was 11.89%. There were significant differences in the history of cerebral infarction, preemptive analgesia, preoperative use of dexmedetomidine, general anesthesia combined with continuous epidural block, duration of surgery, low SpO2 during anesthesia induction, PaCO2 after pneumoperitoneum, postoperative PCEA and VAS score at the third day after operation (all P < .05). Logistic regression analysis revealed that history of cerebral infarction (OR3.12, 1.02∼5.13), low SpO2 during anesthesia induction (OR2.03, 1.19∼4.47), Longer duration of surgery (OR1.82, 1.01∼3.16) were risk factors for POCD in elderly patients with laparoscopic surgery, while postoperative PCEA (OR0.43, 0.01∼0.91), General anesthesia combined with continuous epidural block (OR0.59, 0.04∼0.87), preoperative use of dexmedetomidine (OR0.70, 0.08∼0.94) and preemptive analgesia (OR0.75, 0.13-0.90) were the protective factors for POCD in elderly patients with laparoscopic surgery.For the elderly patients undergoing laparoscopic surgery, the health care providers should be fully alert to the POCD based on those relevant factors.
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http://dx.doi.org/10.1097/MD.0000000000023977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808459PMC
January 2021

Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis.

Front Pediatr 2020 20;8:593435. Epub 2020 Nov 20.

Intensive Care Unit, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD. We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019. Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment. At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.
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http://dx.doi.org/10.3389/fped.2020.593435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715029PMC
November 2020

Evaluation of Extended-Interval Dabigatran Dosing in Older Patients With Non-Valvular Atrial Fibrillation.

J Cardiovasc Pharmacol Ther 2021 Jul 2;26(4):359-364. Epub 2020 Dec 2.

Department of Geriatrics, 26447Peking University First Hospital, Beijing, Xicheng District, China.

Objective: To evaluate the safety and efficacy of extended-interval dabigatran dosing in older Chinese patients with non-valvular atrial fibrillation.

Methods: We conducted an observational study on non-valvular atrial fibrillation patients administered dabigatran at different dosing intervals at the Department of Geriatrics, Peking University First Hospital, China. We enrolled 121 consecutive non-valvular atrial fibrillation patients aged ≥60 years on dabigatran therapy (mean age, 79.6 ± 7.4 years); they were administered conventional low-dose dabigatran (110 mg twice daily) or extended-interval dosing with dabigatran (110 mg every 16 h or every 24 h). All patients received follow-up care, and we evaluated the presence of bleeding and thromboembolic events.

Results: All patients exhibited creatinine clearance greater than 30 mL/min with an average of 56.6 ± 17.3 mL/min. Sixty-two patients received extended-interval dosing with dabigatran at a mean dose of 117.1 ± 18.6 mg daily. Patients on extended-interval dosing were older; they exhibited lower creatinine clearance and bodyweight and higher CHADS-VASc and HAS-BLED scores. The mean follow-up time was 25.8 ± 15.6 months. No significant differences were observed in the trough and peak values of the activated partial thromboplastin time and in thromboembolic or bleeding events between the 2 groups.

Conclusion: Extended-interval dabigatran dosing in older patients with non-valvular atrial fibrillation and lower creatinine clearance can maintain activated partial thromboplastin time trough and peak values comparable to the conventional low dose. Physician-prescribed practices regarding dabigatran dosing intervals do not lead to worse outcomes in the above-mentioned population.
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http://dx.doi.org/10.1177/1074248420977223DOI Listing
July 2021

EGFR inhibitors regulate Ca concentration and apoptosis after PM exposure based on a lung-mimic microfluidic system.

Sci Total Environ 2021 Mar 11;761:143200. Epub 2020 Nov 11.

Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address:

Air pollution has side effects on human health. Epidemiology studies indicate a positive association between ambient fine particle (PM, or particles less than 2.5 μm in diameter) concentration and lung cancer. However, how fine particles affect lung cancer at the molecular level and related therapeutic methods to address these diseases are unclear. Here, the multi-omics analysis (DNA methylation and transcriptomic) was used to detect human bronchial epithelial cells (HBE), that were exposed to PM using a quantified, small, portable, and organ-level air-liquid interface microfluidic system that mimics lung functions. The results indicate that 36,838 differentially methylated genes were detected. Of these 33,796 genes were hypomethylated (beta < 0), and 2862 genes were hypermethylated (beta > 0). RNA-Seq analysis demonstrated that 19,489 genes were upregulated (logFC > 0), and 16,659 were downregulated. Furthermore, the calcium and apoptosis pathways were activated according to multi-omics analysis. The change in EGFR gene expression after PM exposure was the result of alterations of the cellular DNA methylome in the promoter. Inhibition or down-regulation of EGFR could result in the regulation of the downstream intracellular Ca concentration and apoptosis via the EGFR/PLCγ and EGFR/STAT/Bcl-XL pathways after PM exposure. EGFR inhibitors decrease the Ca concentration of cells, thereby strengthening the effects of fine particles on apoptosis. In short, the Ca concentration and the apoptosis of cells can be regulated via EGFR related pathway after PM exposure. The EGFR may be a potentially promising therapeutic target for the treatment of air pollution-induced lung cancer through regulation of the intracellular Ca concentration and apoptosis.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143200DOI Listing
March 2021

Discovery of 12O-A Novel Oral Multi-Kinase Inhibitor for the Treatment of Solid Tumor.

Molecules 2020 Nov 9;25(21). Epub 2020 Nov 9.

Department of Medicinal Chemistry, School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.

A novel series of pyrimidine-benzotriazole derivatives have been synthesized and evaluated for their anticancer activity against human solid tumor cell lines. The most promising molecule was identified for its excellent antiproliferative activities, especially against the SiHa cell line with IC value as 0.009 μM. Kinase inhibition assay assessed was a potential multi-kinase inhibitor, which possessed potent inhibitory activities against cyclin-dependent kinases (CDKs) and fms-like tyrosine kinase (FLT) with IC values in the nanomolar range. Molecular docking studies illustrated that the introduction of triazole moiety in was critical for CDKs inhibition. In addition, inhibited cancer cell proliferation, colony-formation, and cell cycle progression and provoked apoptotic death in vitro. In an SiHa xenograft mouse model, a once-daily dose of compound at 20 mg/kg significantly suppressed the tumor growth without obvious toxicity. Taken together, provided valuable guide for further structural optimization for CDKs and FLT inhibitors.
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http://dx.doi.org/10.3390/molecules25215199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664879PMC
November 2020

Structure and expression analysis of seven salt-related genes of .

PeerJ 2020 20;8:e10206. Epub 2020 Oct 20.

College of Forestry, Shanxi Agricultural University, Taigu, China.

Ethylene response factors (ERFs) are plant-specific transcription factors (TFs) that play important roles in plant growth and stress defense and have received a great amount of attention in recent years. In this study, seven genes related to abiotic stress tolerance and response were identified in plants of the genus. Systematic bioinformatics, including sequence phylogeny, genome organisation, gene structure, gene ontology (GO) annotation, etc. were detected. Expression-pattern of these seven genes were analyzed using RT-qPCR and cross validated using RNA-Seq. Data from a phylogenetic tree and multiple alignment of protein sequences indicated that these seven ERF TFs belong to three subfamilies and contain AP2, YRG, and RAYD conserved domains, which may interact with downstream target genes to regulate the plant stress response. An analysis of the structure and promoter region of these seven genes showed that they have multiple stress-related motifs and -elements, which may play roles in the plant stress-tolerance process through a transcriptional regulation mechanism; moreover, the cellular_component and molecular_function terms associated with these determined by GO annotation supported this hypothesis. In addition, the spatio-temporal expression pattern of these seven , as detected using RT-qPCR and RNA-seq, suggested that they play a critical role in mediating the salt response and tolerance in a dynamic and tissue-specific manner. The results of this study provide a solid basis to explore the functions of the stress-related ERF TFs in abiotic stress tolerance and development process.
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http://dx.doi.org/10.7717/peerj.10206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583627PMC
October 2020

The role of emotion regulation as a mediator between early life stress and posttraumatic stress disorder, depression and anxiety in Syrian refugees.

Transl Psychiatry 2020 11 2;10(1):371. Epub 2020 Nov 2.

Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Early life stress is an important factor in later psychopathology, including symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. The purpose of the present study was to investigate the effect of early life stress on psychiatric symptoms within a sample of Syrian refugees. In this model, the use of cognitive emotion regulation strategies was assessed as a potential mediator of the relationship between early life stress and current symptoms of PTSD, depression, and anxiety. Bootstrap analyses were generated to test the indirect effect of emotion regulation (Cognitive Emotion Regulation Questionnaire) on the relationship between early life stress (Childhood Trauma Questionnaire), PTSD (Harvard Trauma Questionnaire), depressive (PHQ-9) and anxiety (GAD-7) symptoms in eighty-nine Syrian refugees resided in Germany (n = 49) and Jordan (n = 40). The indirect effect of maladaptive strategies was significant between early life stress and psychopathology, whereas the mediation effect of adaptive strategies was not significant. The findings provide an evidence that emotional dysregulation is an underlying factor affecting psychological symptoms in refugees with adverse childhood experiences. These results suggest targeting cognitive emotion regulation in prospective prevention and treatment strategies.
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http://dx.doi.org/10.1038/s41398-020-01062-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606478PMC
November 2020

ECMO-assisted resection of left main bronchial malignant tumor and left pneumonectomy with comprehensive nursing support: a case report.

J Cardiothorac Surg 2020 Oct 6;15(1):300. Epub 2020 Oct 6.

Department of Administration, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, 450003, China.

Background: Patients with Extracorporeal Membrane Oxygenation (ECMO) undergoing primary bronchial malignancy resection and left pneumonectomy via bilateral thoracic approach are rare for there exist few reports available to date. And the nursing experience about this disease is rare reported.

Case Presentation: This study reported a 50-year-old man with adenoid cystic carcinoma in left main bronchus by computed tomography (CT), fiberoptic bronchoscopy, and puncture biopsy. The case is the first report about operation method and the comprehensive nursing care, including conventional nursing, airway management, fluid management, nutritional support, and psychosocial support for patients undergoing primary bronchial malignancy resection and left pneumonectomy. After multidisciplinary treatment and comprehensive care, the patient was cured and discharged on the 17th day after surgery.

Conclusion: This study reported a rare case with bronchial malignancy resection and left pneumonectomy and discussed its nursing care. A skilled management of ECMO, intraoperative position transformation, and prevention, as well as control of pulmonary complications are fundamental in caring patients with bronchial tumors. Monitoring of pulmonary function and blood pressure, adequate nutrition, and psychological support could be contributing factors for successful treatment during the postoperative stage.
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http://dx.doi.org/10.1186/s13019-020-01348-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538043PMC
October 2020

Estimation of infection density and epidemic size of COVID-19 using the back-calculation algorithm.

Health Inf Sci Syst 2020 Dec 28;8(1):28. Epub 2020 Sep 28.

Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94158 USA.

The novel coronavirus (COVID-19) is continuing its spread across the world, claiming more than 160,000 lives and sickening more than 2,400,000 people as of April 21, 2020. Early research has reported a basic reproduction number (R0) between 2.2 to 3.6, implying that the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China in and outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. We also investigate the COVID-19 epidemic size in South Korea and find a similar effect of its "test, trace, isolate, and treat" strategy. Our findings are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.
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http://dx.doi.org/10.1007/s13755-020-00122-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520509PMC
December 2020

In vivo and in vitro anti‑allergic and anti‑inflammatory effects of Dryopteris crassirhizoma through the modulation of the NF‑ĸB signaling pathway in an ovalbumin‑induced allergic asthma mouse model.

Mol Med Rep 2020 Nov 25;22(5):3597-3606. Epub 2020 Aug 25.

Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea.

Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, anti‑influenza virus, anti‑tumor, anti‑reverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)‑induced allergic asthma mouse model and phorbol myristate acetate (PMA)‑ and A23187‑stimulated HMC‑1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL‑10 and interferon (IFN)‑γ) and decreased the levels Th2 cytokines (IL‑4, IL‑5 and IL‑13) and proinflammatory cytokines (IL‑6 and TNF‑α). Furthermore, DC treatment inhibited the activation of NF‑κB signaling (NF‑κB, p‑NF‑κB, IκB and p‑IκB), both in BALF and lung homogenates. Serum levels of total IgE and OVA‑specific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the anti‑inflammatory effect of OVA‑specific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL‑6 and TNF‑α, and the activation of NF‑κB signaling (NF‑κB and p‑NF‑κB), in PMA and calcium ionophore A23187‑stimulated HMC‑1 cells. In summary, the current study demonstrated that DC acts a potent anti‑allergic and anti‑inflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187‑stimulated HMC‑1 cells via NF‑κB signaling in an OVA‑induced allergic asthma model.
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http://dx.doi.org/10.3892/mmr.2020.11460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533436PMC
November 2020