Publications by authors named "Yuan Li"

4,109 Publications

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Caloric restriction alleviates radiation injuries in a sex-dependent fashion.

FASEB J 2021 Aug;35(8):e21787

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.
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http://dx.doi.org/10.1096/fj.202100351RRDOI Listing
August 2021

IRF1 inhibits autophagy-mediated proliferation of colorectal cancer via targeting ATG13.

Cancer Invest 2021 Jul 27:1-18. Epub 2021 Jul 27.

Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.

IRF1 is a nuclear transcription factor that mediates interferon effects and appears to have anti-tumor activity. To determine the roles of IRF1 in colorectal cancer (CRC), we investigated the effects of IRF1 in CRC cells. We found that IRF1 inhibit cell proliferation and tumor growth. Under starvation conditions, IRF1 enhanced apoptosis and reduced autophagic flux. ATG13, an important factors of autophagy complex, was confirmed as a target of IRF1. These findings indicated that IRF1 function as a tumor suppressor in CRC and inhibit autophagy through ATG13, targeting this pathway may provide new insights into the molecular mechanisms of CRC progression.
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http://dx.doi.org/10.1080/07357907.2021.1961265DOI Listing
July 2021

Deep learning-based evaluation of the relationship between mandibular third molar and mandibular canal on CBCT.

Clin Oral Investig 2021 Jul 27. Epub 2021 Jul 27.

Center for TMD and Orofacial Pain, Department of Oral and Maxillofacial Radiology, Peking University School and Hospital of Stomatology, No. 22 Zhong Guan Cun South Ave, Beijing, 100081, People's Republic of China.

Objectives: The objective of our study was to develop and validate a deep learning approach based on convolutional neural networks (CNNs) for automatic detection of the mandibular third molar (M3) and the mandibular canal (MC) and evaluation of the relationship between them on CBCT.

Materials And Methods: A dataset of 254 CBCT scans with annotations by radiologists was used for the training, the validation, and the test. The proposed approach consisted of two modules: (1) detection and pixel-wise segmentation of M3 and MC based on U-Nets; (2) M3-MC relation classification based on ResNet-34. The performances were evaluated with the test set. The classification performance of our approach was compared with two residents in oral and maxillofacial radiology.

Results: For segmentation performance, the M3 had a mean Dice similarity coefficient (mDSC) of 0.9730 and a mean intersection over union (mIoU) of 0.9606; the MC had a mDSC of 0.9248 and a mIoU of 0.9003. The classification models achieved a mean sensitivity of 90.2%, a mean specificity of 95.0%, and a mean accuracy of 93.3%, which was on par with the residents.

Conclusions: Our approach based on CNNs demonstrated an encouraging performance for the automatic detection and evaluation of the M3 and MC on CBCT. Clinical relevance An automated approach based on CNNs for detection and evaluation of M3 and MC on CBCT has been established, which can be utilized to improve diagnostic efficiency and facilitate the precision diagnosis and treatment of M3.
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http://dx.doi.org/10.1007/s00784-021-04082-5DOI Listing
July 2021

[Characteristics and Sources of VOCs at Different Ozone Concentration Levels in Tianjin].

Huan Jing Ke Xue 2021 Aug;42(8):3585-3594

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

To further study the effect of volatile organic compounds (VOCs) on ozone pollution, the characteristics and sources of VOCs at different ozone (O) concentration levels were analyzed, using high-resolution online monitoring data obtained from Tianjin in the summer of 2019. Results showed that VOCs concentrations were 32.94, 38.10, 42.41, and 47.12 μg ·m, when the O concentration levels were categorized as excellent, good, light pollution, and moderate pollution, respectively. VOCs were composed of alkanes, alkenes, alkynes and aromatics, which accounted for 61.72%-63.36%, 14.96%-15.51%, 2.73%-4.13%, and 18.53%-19.10%, respectively, of VOCs concentrations at different O concentration levels. Among them, the proportion of alkanes was slightly higher when O concentration was categorized as good or light pollution, alkenes and alkynes accounted for the highest proportion when O concentration was excellent, and the proportion of aromatics was highest during periods of moderate pollution. The main VOCs species were propane, ethane, ethylene, toluent, -butane, isopentane, /-xylene, propylene, acetylene, -hexane, isobutene, benzene, -pentane, isoprene, and 1,2,3-trimethylbenzene. The concentration percentage of isopentane, -pentane, benzene, ethylene, propylene, -butane, and isobutane increased gradually as O concentration increased. Significant increases in isoprene and 1,2,3-trimethylbenzene were observed during periods of light and moderate pollution. Alkenes and aromatics had higher ozone formation potential (OFP), and the contribution of alkenes to OFP declined as the O level rose, whereas that of aromatics increased. Ethylene, propylene, /-xylene, 1,2,3-trimethylbenzene, toluene, isoprene, -2-butene, and -2-pentene were the key species for O generation, and the contribution ratio of 1,2,3-trimethylbenzene, isoprene, propylene, and ethylene to OFP increased significantly during light or moderate O pollution. Positive matrix factorization was applied to estimate the source contributions of VOCs. Automobile exhaust, solvent usage, liquefied petroleum gas (LPG)/gasoline evaporation, combustion, petrochemical industrial emissions, natural sources, and other industrial emissions were identified as major sources of VOCs in summer. As O concentration level rose, the contribution percentage of automobile exhaust, LPG/gasoline evaporation, petrochemical industrial emissions, and natural sources increased gradually, whereas the contribution of combustion and other industrial emissions decreased overall. The contribution of solvent usage was lower when O levels indicated light or moderate pollution than when it was good.
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http://dx.doi.org/10.13227/j.hjkx.202101129DOI Listing
August 2021

Validation of the Novel IASLC Grading System for Invasive Pulmonary Adenocarcinoma and Association with Common Driver Mutations.

J Thorac Oncol 2021 Jul 21. Epub 2021 Jul 21.

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, 200032, China;; Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, China;; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China;. Electronic address:

Introduction: We aimed to validate the utility of the novel grading system proposed by the International Association for the Study of Lung Cancer (IASLC) pathology committee for prognosis stratification of invasive pulmonary adenocarcinomas (ADCs) in Chinese patients. Correlations between the grading system, common driver mutations and adjuvant chemotherapy (ACT) were also investigated.

Methods: From 2008 to 2016, the histologic patterns of a large cohort of 950 patients with invasive ADCs (stages I to III) were retrospectively analyzed and classified according to the proposed grading system. Subsequently, tumor grading was correlated with genetic data, ACT, and patient outcome.

Results: Compared with conventional predominant pattern-based groups, the novel grading system carried improved survival discrimination (area under the curve [AUC] = 0.768 for recurrence-free survival and 0.775 for overall survival). The AUC curve was not further improved when incorporated lymphovascular invasion status. EGFR mutations (P<.001) were correlated with moderate grade while KRAS mutations (P=.041) and ALK fusions (P=.021) were significantly more prevalent in poor grade. The reclassification of grading system based on EGFR mutation status demonstrated excellent survival discrimination (P<.001). In particular, stage Ib-III patients with novel high-grade ADCs had an improved prognosis with ACT.

Conclusions: The novel IASLC grading system is a practical and efficient discriminator for patient prognosis and should be part of an integrated pathologic-genetic subtyping to improve survival prediction. In addition, it may support patient stratification for aggressive adjuvant chemotherapy.
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http://dx.doi.org/10.1016/j.jtho.2021.07.006DOI Listing
July 2021

Cu-modified MOF as laccase-mimicking material for colorimetric determination and discrimination of phenolic compounds with 4-aminoantipyrine.

Mikrochim Acta 2021 Jul 24;188(8):272. Epub 2021 Jul 24.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, People's Republic of China.

Based on the laccase-mimicking activity of Cu-modified University of Oslo (UiO) metal-organic framework (UiO-67-Cu), we developed a colorimetric sensor array for distinguishing a series of phenols with different number and position of substituted hydroxyl group (-OH) and different substituent group on the benzene ring, including phenol, catechol, quinol, resorcinol, pyrogallol, phloroglucinol, o-chlorophenol, o-aminophenol, and o-nitrophenol. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of phenolic compounds were obtained by theoretical calculation. The results show that the lower the LUMO energy level, the easier the chromogenic reaction occurs. The UiO-67-Cu-catalyzed phenol chromogenic reaction showed a good linearity in the range from 0.1 to 200 μM with limit of detection approximately 61 nM. Through the detection of phenol in tap water and river water, the recovery rate and RSD (n = 3) were calculated as 94.1~103% and 1.0~3.3, respectively, showing good recovery, reliable results, and outstanding stability. Therefore, the proposed colorimetric sensor array will have a great potential for the detection of phenols in the environment. Schematic presentation of a simple and sensitive colorimetric strategy based on the laccase-mimicking activity of Cu-modified UiO-type metal-organic framework (MOFs, Uio-67-Cu) to distinguish phenols with analogous structures.
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http://dx.doi.org/10.1007/s00604-021-04944-5DOI Listing
July 2021

The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma.

Int J Mol Sci 2021 Jul 10;22(14). Epub 2021 Jul 10.

Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Department of Biopharmaceuticals, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling. Therefore, aberrant trimethylation at H3K9 due to amplification, mutation or deletion of SETDB1 may lead to transcriptional repression of various tumour-suppressing genes and other related genes in cancer cells. Lung cancer is the most common type of cancer worldwide in which SETDB1 amplification and H3K9 hypermethylation have been indicated as potential tumourigenesis markers. In contrast, frequent inactivation mutations of SETDB1 have been revealed in mesothelioma, an asbestos-associated, locally aggressive, highly lethal, and notoriously chemotherapy-resistant cancer. Above all, the different statuses of SETDB1 indicate that it may have different biological functions and be a potential diagnostic biomarker and therapeutic target in lung cancer and mesothelioma.
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http://dx.doi.org/10.3390/ijms22147416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306223PMC
July 2021

IF1 inactivation attenuates experimental colitis through downregulation of neutrophil infiltration in colon mucosa.

Int Immunopharmacol 2021 Jul 20;99:107980. Epub 2021 Jul 20.

Metabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou 450007, China. Electronic address:

IF1 is a mitochondrial protein involved in the regulation of ATP synthase activity. The role of IF1 remains to be established in inflammatory bowel diseases (IBD). In this study, we report that IF1 gene inactivation generated protection against IBD in the dextran sodium sulfate (DSS) model. IF1 gene knockout (IF1-KO) mice developed less severe colitis than the wild type (WT) mice as judged by parameters including disease activity index (DAI), body weight loss, inflammatory cytokines, leukocyte infiltration and bacterial invasion in the colon tissue. The intestinal barrier integrity was protected in the colon tissue of IF1-KO mice through a reduction in apoptosis and inflammasomal activity. The protection was abolished in the KO mice after substitution of the immune cells with the wild type cells following bone marrow transplantation. Depletion of neutrophils with anti-Gr-1 antibody abolished the protection from colitis in IF1-KO mice. Neutrophil number was decreased in the peripheral blood of IF1-KO mice, which was associated with a reduction in LC3A/B proteins in the KO neutrophils in Rapamycin-induced autophagy response. Inhibition of autophagy with the lysosome inhibitor Chloroquine (CQ) decreased the absolute number of neutrophils in WT mice and protected the mice from colitis. Taken together, these findings suggest that IF1 may contribute to the pathogenesis of IBD through acceleration of neutrophil autophagy. The activity is attenuated in the IF1-KO mice through reduction of autophagy in neutrophils leading to resistance to IBD.
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http://dx.doi.org/10.1016/j.intimp.2021.107980DOI Listing
July 2021

Effect of glutamic acid on the preparation and characterization of Pickering emulsions stabilized by zein.

Food Chem 2021 Jul 15;366:130598. Epub 2021 Jul 15.

School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China. Electronic address:

In this study, glutamic acid and zein were utilized to prepare colloidal nanoparticles as stabilizers for Pickering emulsions. The effect of the ratio of glutamic acid to zein on the stability, zeta potential, particle size, morphology, and structure of colloidal nanoparticles was studied. The results showed that zein and glutamic acid combined in the form of noncovalent bonds, which changed the characteristics of the zein. In addition, colloidal particles aggregation was induced by glutamic acid, which altered the distribution of droplets in the emulsion, and increased the adsorption of proteins on the surface of the oil droplets, as reflected by the analysis of the size, microstructure, rheological behaviours, and driving force of the Pickering emulsion. Hydrophobic interactions and electrostatic interactions were the main driving forces for the formation of colloidal particles, which was determined by driving force analysis and the change of the zeta potential.
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http://dx.doi.org/10.1016/j.foodchem.2021.130598DOI Listing
July 2021

Connexin26 Modulates the Radiosensitivity of Cutaneous Squamous Cell Carcinoma by Regulating the Activation of the MAPK/NF-κB Signaling Pathway.

Front Cell Dev Biol 2021 5;9:672571. Epub 2021 Jul 5.

Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

Previous studies have confirmed that the gap junction protein Connexin26 (Cx26) is specifically expressed in human skin tissue. Cx26 can transmit radiation-induced damage signals. However, no study has yet reported whether Cx26 expression affects the radiosensitivity of human skin squamous cancer cells or the mechanism by which this occurs. In this study, we found that human skin squamous cell carcinoma cells (A431 cells) expressed significantly more Cx26 and were more sensitive to radiation compared to normal human keratinocytes (HaCaT cells). Knockdown of Cx26 in A431 cells (A431) decreased radiosensitivity relative to control cells and altered the expression of key proteins in the MAPK and NF-κB signaling pathways. These results demonstrate that Cx26 expression might play an important role in mediating radiation damage in A431 cells and could serve as a potential target for clinical radiotherapy for cutaneous squamous cell carcinoma.
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http://dx.doi.org/10.3389/fcell.2021.672571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287175PMC
July 2021

Nuclear NAD homeostasis governed by NMNAT1 prevents apoptosis of acute myeloid leukemia stem cells.

Sci Adv 2021 Jul 21;7(30). Epub 2021 Jul 21.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Metabolic dysregulation underlies malignant phenotypes attributed to cancer stem cells, such as unlimited proliferation and differentiation blockade. Here, we demonstrate that NAD metabolism enables acute myeloid leukemia (AML) to evade apoptosis, another hallmark of cancer stem cells. We integrated whole-genome CRISPR screening and pan-cancer genetic dependency mapping to identify and as AML dependencies governing NAD biosynthesis. While both and were required for AML, the presence of NAD precursors bypassed the dependence of AML on but not , pointing to as a gatekeeper of NAD biosynthesis. Deletion of reduced nuclear NAD, activated p53, and increased venetoclax sensitivity. Conversely, increased NAD biosynthesis promoted venetoclax resistance. Unlike leukemia stem cells (LSCs) in both murine and human AML xenograft models, was dispensable for hematopoietic stem cells and hematopoiesis. Our findings identify NMNAT1 as a previously unidentified therapeutic target that maintains NAD for AML progression and chemoresistance.
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http://dx.doi.org/10.1126/sciadv.abf3895DOI Listing
July 2021

Comparison of pediatric empyema secondary to tuberculosis or non-tuberculosis community-acquired pneumonia who underwent surgery in high TB burden areas.

Pediatr Pulmonol 2021 Jul 21. Epub 2021 Jul 21.

Department of Pediatric Surgery, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.

Introduction: Tuberculous empyema (TE) in children is common in high-TB burden and medical resource limited areas. However, studies that evaluate the characteristics of TE in children are sparse. This study aimed to analyze the clinical features of pediatric TE receiving surgical intervention.

Methods: We performed a retrospective study of children with empyema secondary to community-acquired pneumonia (CAP) who underwent surgery in our institution. The clinical characteristics were compared between TE and empyema secondary non-tuberculosis infection (non-tuberculosis empyema, NTE).

Results: One hundred patients were included (27 with TE and 73 with NTE). The stage 3 empyema occupied 81.5% and 45.2% of TE and NTE in this study. The TE children had older age, longer duration of illness, and milder symptoms. Pleural fluid culture was positive for Mycobacterium tuberculosis in 7.4% of patients with TE. Lymph node enlargement, lymph node calcification and pleural nodules presented in TE with high specificity (93.2, 98.6, and 98.5%) but low sensitivity (33.3, 14.8, and 29.6%) on CT scan. Thoracoscopy surgery was performed in 14 (51.9%) in TE and 39 (53.4%) in NTE. Postoperative chest-tube indwelling time was longer (7.85 ± 5.00 vs. 4.89 ± 1.81 days, P < 0.001), and more patients had incomplete lung expansion after 3 months in TE.

Conclusion: Tuberculosis infection should be screened in management of children with empyema in high-TB burden areas. Pediatric TE usually presented in older age and with milder respiratory symptoms. Pleural biopsy during surgery is often necessary to confirm the cause of infection. Thoracotomy is still required in some pediatric TE or NTE with delayed treatment in medical resource limited area. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ppul.25591DOI Listing
July 2021

Microglia NLRP3 Inflammasomes Activation Involving Diabetic Neuroinflammation in Diabetic Mice and BV2 Cells.

Curr Pharm Des 2021 Jul 15. Epub 2021 Jul 15.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University; Department of Endocrinology, Department of Interventional Therapy, Department of Infectious Diseases, First Hospital of Jilin University, Changchun 130000, China.

Background: Hyperglycemia-induced microglia activation can cause a continuous release of proinflammatory cytokines, which gradually damages neurons and contributes to central diabetic neuroinflammation.

Objective: This study aimed to illustrate the possible mechanism related to NLRP3 inflammasome and the aggravation of diabetes neuroinflammation.

Methods: The targeted proteins from BV2 cells and brain tissues were tested by Western blot or immunohistochemistry. Cytokines from cell supernatant and serum were detected by ELISA. Meanwhile, cytoplasm and mitochondria ROS were determined by DCFHDA and Mito sox Red, respectively.

Results: In vitro, BV2 cells were stimulated by different glucose concentrations (5.5 to 65 mM/L) above physiological values and maintained for different periods (12 to 48h). The proinflammatory cytokines IL-1β,IL18,IL6,TNFα and cytoplasm ROS were significantly increased in a dose-dependent manner, while mitochondrial ROS was unaffected. NLRP3 inflammasomes, MAPKs, and NF-κB pathways were obviously activated at the concentration of 35 mM/L for 12h. Inhibition assay using specific inhibitors indicated that the treatment of glucose (35 mM/L for 12h) could stimulate NLRP3 inflammasome activation via ROS/JNK MAPKs/NF-κB pathway. In STZ induced diabetes mice models, microglia NLRP3, ASC, and caspase-1 proteins were highly expressed, and serum cytokines IL-1β, IL6, IL18, and TNFα were remarkably increased.

Conclusion: Microglia NLRP3 inflammasomes activation involves diabetic neuroinflammation in diabetic mice and BV2 cells via ROS/JNK MAPKs/NF-κB pathways.
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http://dx.doi.org/10.2174/1381612827666210716104606DOI Listing
July 2021

Collagen sponge prolongs taurine release for improved wound healing through inflammation inhibition and proliferation stimulation.

Ann Transl Med 2021 Jun;9(12):1010

Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Attenuating oxidative stress response is an effective strategy for the treatment of wounds. Taurine is a widely abundant amino acid in mammal species, capable of inhibiting oxygen-free radicals during the inflammation phase.

Methods: A novel taurine carried biocompatible composite collagen-derived sponge, [email protected], was fabricated for the treatment of a full-thickness removal mouse wounds model. experiments included taurine release from [email protected] and cell viability when co-cultured with [email protected] With the prolonged release of taurine upon the wound site, [email protected] was engineered to perform well in the wound site through inflammation inhibition and proliferation stimulation as demonstrated by a series of histological staining.

Results: taurine release profile and good cell biocompatibility of [email protected] were demonstrated. studies showed that [email protected] indeed sped up the process of wound regeneration through enhanced granulation formation, collagen deposition as well as re-epithelialization. Further investigations through immunofluorescence staining revealed that the improved wound healing ability of [email protected] was mediated by the enhanced cell proliferation via the upregulation of endogenous vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β) expression as well as decreased inflammatory response through stimulated M2 polarization of macrophages.

Conclusions: This engineered [email protected] delivery system has great potential as a wound dressing in future applications.
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http://dx.doi.org/10.21037/atm-21-2739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267268PMC
June 2021

Soluble ST2 and mixed venous oxygen saturation for prediction of mortality in patients with pulmonary hypertension.

J Thorac Dis 2021 Jun;13(6):3478-3488

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Background: Although soluble suppression of tumorigenicity-2 (sST2) has been identified as a clinical biomarker for pulmonary hypertension (PH) by previous studies, the implication of sST2 combined with hemodynamic parameters in PH has not been well studied. This study aimed to evaluate the relationship between sST2 and hemodynamic parameters and to evaluate the predictive value of sST2 for mortality in patients with PH.

Methods: One hundred eighty-four incident patients with PH and 14 healthy controls were retrospectively enrolled by Shanghai Pulmonary Hospital for this retrospective study. After all patients underwent right heart catheterization, blood samples were collected and serum sST2 concentration was assessed by the Presage™ ST2 assay. Kaplan-Meier curve and Cox regression analyses were used to predict survival and the association between survival and different factors such as sST2, SvO.

Results: During a follow-up of 44.9 (IQR 28.5-64.4) months, 65 patients died. The median concentration of sST2 in PH patients was 33.1 ng/mL, which is higher than that in control group (23.1 ng/mL, P=0.005). Furthermore, for PH group, the level of sST2 was higher in non-survivors than that in survivors. Cox regression analyses demonstrated that sST2 and SvO were independent risk factors for survival. In Kaplan-Meier curve analyses, elevated sST2 level and reduced SvO predicted a poor outcome for patients with PH.

Conclusions: Higher sST2 was independently associated with increased mortality, as well as lower SvO in patients with PH. Especially, the combination of higher sST2 and lower SvO had the strongest predictive value of mortality in patients with PH.
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http://dx.doi.org/10.21037/jtd-20-2732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264676PMC
June 2021

Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study.

Front Pharmacol 2021 2;12:581833. Epub 2021 Jul 2.

Department of Nephropathy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care. In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide 16.7% for grp 1 patients (2/12) ( = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 ( 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 ( 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14-28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.
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http://dx.doi.org/10.3389/fphar.2021.581833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284962PMC
July 2021

Long-term trend of heat waves and potential effects on phytoplankton blooms in Lake Qiandaohu, a key drinking water reservoir.

Environ Sci Pollut Res Int 2021 Jul 16. Epub 2021 Jul 16.

Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China.

Global warming is increasing the frequency and duration of heat waves, which is defined as when air temperature exceeds a threshold for more than specific consecutive days. Ecosystem around the globe will be impaired by heat waves just like the exposures to dangerously high temperatures as a public health threat to human. However, the knowledge of the response of lake and reservoir ecosystem to heat waves is largely unknown although it has been argued that climate warming may increase the incidence of harmful algal blooms. We examined the long-term trend of heat waves and how the variability of phytoplankton biomass responds to lake heat waves on a deep reservoir (Lake Qiandaohu). Long-term (1980-2020) meteorological observation in the lake watershed showed a significant warming trend of 0.36 °C per decade for the yearly average of daily average air temperature and the yearly average of daily maximum air temperature of 18.32 °C was observed in 2016. Meanwhile, a significant increasing number of heat wave events lasting longer was observed, and Lake Qiandaohu suffered an unusually severe lake heat wave in summer 2016. Significant correlations were found between the yearly average of daily maximum air temperature and heat days, heat wave events, and heat wave days. Nuisance phytoplankton bloom was found in Lake Qiandaohu by high frequency observation and remote sensing monitoring in summer 2016. Remote sensing estimation from two Landsat 8 Operational Land Imager (OLI) images showed that the average chlorophyll a (Chla) was 7.45 ± 4.89 μg/L on July 18 before heat wave and 18.96 ± 0.98 μg/L on August 19 during the heat wave. Two heat wave events lasting from July 20 to August 2 and August 11 to 26 with average surface water temperature of 29.93 and 31.99 °C promoted two marked phytoplankton blooms with average Chla concentrations of 11.75 ± 4.08 and 10.53 ± 1.65 μg/L in the central lake region, respectively, as evidenced by high-frequency buoy data. These findings suggest that heat waves are likely to yield an increased threat of harmful algal bloom in freshwater ecosystems. With lake heat waves projected to increase in frequency, duration, and spatial extent with global climate change, more studies are needed to improve our understanding of lake heat waves and their potential effects on the species, communities, frequency of phytoplankton bloom, and also help providing advanced schemes of water quality management.
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http://dx.doi.org/10.1007/s11356-021-15414-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284419PMC
July 2021

Melatonin prevents peri‑implantitis via suppression of TLR4/NF-κB.

Acta Biomater 2021 Jul 14. Epub 2021 Jul 14.

Department of Implant Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China. Electronic address:

Peri‑implantitis, which is characterized by peri‑implant mucositis and alveolar bone resorption, significantly shortens the service life of dental implants. Melatonin is well-known for its anti-inflammatory and osteoprotective activities. Nevertheless, the effects and mechanisms of melatonin to prevent peri‑implantitis remain unknown. In this study, the lipopolysaccharide-induced peri‑implantitis model was established after the titanium implants were osseointegrated, and the rats received daily administrations of melatonin. The gingival fibroblasts and osteoclasts/osteoblasts were also co-cultured to simulate the inflammatory environment in vitro. We found that prophylactic administration of melatonin decreased proinflammatory cytokine levels and osteoclast numbers, attenuated alveolar bone resorption, and reduced the incidence of peri‑implantitis in vivo. Furthermore, melatonin suppressed osteoclastic formation and function in the inflammatory co-culture environment, while melatonin promoted osteoblastic differentiation and function in the in vitro model. Mechanistically, melatonin reduced TLR4 protein levels, and inhibited activation of NF-κB to downregulate the levels of TNF, IL-1β, and IL-6. These data showed that melatonin was a potent agent to prevent peri‑implantitis through inhibiting TLR4/NF-κB signaling. Our findings provide a novel strategy to prevent peri‑implantitis, and expand the applications of melatonin. STATEMENT OF SIGNIFICANCE: Dental implants have become the first choice for restoring partial and full edentulism, but its service life is seriously affected by peri‑implantitis. Exploration of novel and effective approaches to prevent peri‑implantitis is an important and urgent need. In the present study, we have reported for the first time that prophylactic administration of melatonin delayed the occurrence and reduced the incidence of peri‑implantitis by decreasing proinflammatory cytokine levels, inhibiting osteoclastogenesis, and promoting osteogenesis. The study is expected to have an important significance on the prevention of peri‑implantitis.
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http://dx.doi.org/10.1016/j.actbio.2021.07.017DOI Listing
July 2021

Angiotensin II -induced overexpression of Sirtuin-1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells.

Am J Physiol Heart Circ Physiol 2021 07 16. Epub 2021 Jul 16.

Department of Pharmacology and Physiology, Faculty of Medicine, University of Montréal, Montréal, Montreal, Quebec, Canada.

Angiotensin II (Ang II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMC) through the overexpression of Giα proteins. Sirtuin1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMC as well as in Ang II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in Ang II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMC. We show that Ang II treatment of VSMC increased the expression of Sirt1 which was attenuated by AT1 and AT2 receptor antagonists, losartan and PD123319 respectively. In addition, knockdown of Sirt1 by siRNA attenuated Ang II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMC as well as the overexpression of cell cycle proteins, cyclin D1, Cdk4 and phosphorylated retinoblastoma proteins. Furthermore, Ang II-induced increased levels of superoxide anion (O) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and AKT that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMC were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated Ang II-induced enhanced phosphorylation of PDGFR, EGFR and IGFR in VSMC. In summary, our results demonstrate that Ang II increased the expression of Sirt1 which through oxidative stress, growth factor receptor-mediated MAP kinase/AKT signaling pathway enhances the expression of Giα proteins and cell cycle proteins and results in the hyperproliferation of VSMC.
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http://dx.doi.org/10.1152/ajpheart.00898.2020DOI Listing
July 2021

Two-Dimensional Gel Electrophoresis and Pro-Q Diamond Phosphoprotein Stain-Based Plant Phosphoproteomics.

Authors:
Yuan Li Dongtao Ren

Methods Mol Biol 2021 ;2358:159-168

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, China.

Pro-Q diamond phosphoprotein gel stain is a fluorescent stain to detect phosphorylated proteins in polyacrylamide gels with high sensitivity. Here, we describe an entire procedure for phosphoproteomics analysis of Arabidopsis seedlings by a combination of Pro-Q diamond stain and two-dimensional gel electrophoresis (2-DE). The workflow involves total protein preparation, protein separation by 2-DE, the second-dimensional gel staining, phosphoproteins detection, and peptides preparation for matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Approximately 300 phosphoproteins can be detected using this method.
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http://dx.doi.org/10.1007/978-1-0716-1625-3_11DOI Listing
January 2021

Time and residual hematopoiesis are crucial for PNH clones escape in hepatitis-associated aplastic anemia.

Ann Hematol 2021 Jul 16. Epub 2021 Jul 16.

State Key Laboratory of Experimental Hematology, Department of Anemia Therapeutic Center, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

The presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) suggests immunopathogenesis, but when and how PNH clones emerge and proliferate are unclear. Hepatitis-associated aplastic anemia (HAAA) is a special variant of AA, contrarily to idiopathic AA, in HAAA the trigger for immune activation is clearer and represented by the hepatitis and thus serves as a good model for studying PNH clones. Ninety HAAA patients were enrolled, including 61 males and 29 females (median age 21 years). Four hundred three of idiopathic AA have been included as controls. The median time from hepatitis to cytopenia was 50 days (range 0-180 days) and from cytopenia to AA diagnosis was 26 days (range 2-370 days). PNH clones were detected in 8 HAAA patients (8.9%) at diagnosis and in 73 patients with idiopathic AA (IAA) (18.1%). PNH cells accounted for 4.2% (1.09-12.33%) of red cells and/or granulocytes and were more likely to be detected in patients with longer disease history and less severe disease. During follow-up, the cumulative incidence of PNH clones in HAAA increased to 18.9% (17/90). Nine HAAA patients newly developed PNH clones, including six immunosuppressive therapy (IST) nonresponders. The clone size was mostly stable during follow-up, and only 2 of 14 patients showed increased clone size without proof of hemolysis. In conclusion, PNH clones were infrequent in newly diagnosed HAAA, but their frequency increased to one that was similar to the IAA frequency during follow-up. These results suggest that the PNH clone selection/expansion process is dynamic and takes time to establish, confirming that retesting for PNH clones during follow-up is crucial.
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http://dx.doi.org/10.1007/s00277-021-04553-5DOI Listing
July 2021

Comparison of Levitt's CO Breath Test and the N-Glycine Labeling Technique for Measuring the Lifespan of Human Red Blood Cells.

Am J Hematol 2021 Jul 15. Epub 2021 Jul 15.

Anemia Therapeutic Centre, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. To compare the CO breath test and N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods were analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the N-glycine labeling technique. The RBC lifespan values determined from the N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R=0.98 (p<0.05), while the R of the linear regression equation was 0.96. The CO breath test as good performance as the N-glycine labelling technique in order to distinguish healthy from haemolysis subjects. The result suggesting that the CO breath test is a reliable method (might be used) for quickly determining human RBC lifespans in clinical applications. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ajh.26290DOI Listing
July 2021

Analysis of fluorescence simulation and experiments for sea surface oil film based on LIF.

Appl Opt 2021 Jun;60(18):5439-5450

In order to effectively analyze the fluorescence distribution of sea surface oil film detected by laser-induced fluorescence (LIF), a novel, to the best of our knowledge, simulation model of the oil film fluorescence was established based on the Monte Carlo method. Using this simulation model, the fluorescence distribution of oil film with different thickness in emission direction and spatial distribution were analyzed. Based on the fluorescence mechanism model of oil film detected by LIF, a criterion for the LIF system calibration, i.e., the fluorescence intensity ratio between oil film and clean seawater (FIR) using the fluorescence collected from clean seawater as a reference was proposed. The validity of the fluorescence simulation model was verified by using the FIR results of theory and simulation. The fluorescence spectra of oil films with different thickness and FIR parameters of corresponding thickness were obtained by experiments. By analyzing the fluorescence spectra of different oil products and oil film thickness, the fluorescence influencing factors of oil film detected by LIF were obtained. The results show that the fluorescence coverage area increases gradually with the increase of oil film thickness. When the incident light is in the same direction as the fluorescence receiving direction, the obtained fluorescence intensity is larger. Moreover, the FIR used as the calibration criterion of the LIF monitoring system can effectively characterize the thickness of oil film on the sea surface for LIF to detect sea surface oil film in real applications.
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http://dx.doi.org/10.1364/AO.426451DOI Listing
June 2021

LYG1 Deficiency Attenuates the Severity of Acute Graft-Versus-Host Disease Skewing Allogeneic T Cells Polarization Towards Treg Cells.

Front Immunol 2021 28;12:647894. Epub 2021 Jun 28.

Department of Hematology, Peking University First Hospital, Beijing, China.

Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation. The mechanism involves the recognition of host antigens by donor-derived T cells which induces augmented response of alloreactive T cells. In this study, we characterized the role of a previously identified novel classical secretory protein with antitumor function-LYG1 (Lysozyme G-like 1), in aGVHD. LYG1 deficiency reduced the activation of CD4 T cells and Th1 ratio, but increased Treg ratio by MLR assay. By using major MHC mismatched aGVHD model, LYG1 deficiency in donor T cells or CD4 T cells attenuated aGVHD severity, inhibited CD4 T cells activation and IFN-γ expression, promoted FoxP3 expression, suppressed CXCL9 and CXCL10 expression, restrained allogeneic CD4 T cells infiltrating in target organs. The function of LYG1 in aGVHD was also confirmed using haploidentical transplant model. Furthermore, administration of recombinant human LYG1 protein intraperitoneally aggravated aGVHD by promoting IFN-γ production and inhibiting FoxP3 expression. The effect of rhLYG1 could partially be abrogated with the absence of IFN-γ. Furthermore, LYG1 deficiency in donor T cells preserved graft-versus-tumor response. In summary, our results indicate LYG1 regulates aGVHD by the alloreactivity of CD4 T cells and the balance of Th1 and Treg differentiation of allogeneic CD4 T cells, targeting LYG1 maybe a novel therapeutic strategy for preventing aGVHD.
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http://dx.doi.org/10.3389/fimmu.2021.647894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273552PMC
June 2021

Activity Screening of the Herb and an Analysis of Its Antitumor Effects.

Evid Based Complement Alternat Med 2021 25;2021:9939345. Epub 2021 Jun 25.

Guizhou University of Traditional Chinese Medicine, Guian District, Guiyang 550025, China.

Aim: Traditionally, medicine was the heartwood, which needs to be cut down as a whole. In this research, the antitumor activity and mechanisms of the leaves and stems were compared with the roots of ; it was in order to investigate whether stems and leaves of could be used to replace heartwood for antitumor treatment, thereby reducing resource destruction.

Methods: MTT assays were used to identify the active sites of based on the application of human liver cancer (HuH-7) cells. High-performance liquid chromatography (HPLC) was used to analyze polar extracts. We also established a H22 hepatoma-bearing mouse model by administering intraperitoneal injections of petroleum ether extracts from the leaves and stems (SY②) at doses of 20 and 65 mg/kg. Mice in the i.g. group were administered intragastrically with the same extracts (at doses of 100 and 325 mg/kg) at the same time (12 days).

Results: The antitumor site of was the petroleum ether extract. The IC for the petroleum ether extract of roots (SG②) was 56.10 g/ml, while that for the leaves and stems (SY②) was 77.20 g/ml. Grey relational analysis indicated 11 active fraction peaks that were closely related to antitumor activity. The size of tumors in H22 hepatoma-bearing mice was reduced significantly in mice administered with petroleum ether extracts from the leaves and stems (inhibition rates of high doses were 55.31% and 60.56%). Fibrous tissue proliferation, inflammatory cell infiltration, tumor cell necrosis, and the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were all lower than in the control group (VEGF  < 0.001 and PCNA  < 0.05).

Conclusion: Petroleum ether extracts of the roots, leaves, and stems of exhibit certain antitumor effects. Our data indicate that the mechanisms underlying these effects may relate to a reduction in the expression of PCNA and VEGF and the inhibition of angiogenesis. Our findings indicate that we can expand the medicinal use of to the leaves and stems, thus improving resource utilization and reducing resource damage.
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http://dx.doi.org/10.1155/2021/9939345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257350PMC
June 2021

Effects of adding sodium nitrite and tea polyphenols on the characterizations and cytotoxicity of carbon nanoparticles from fried pork.

Food Chem 2021 Jun 25;365:130464. Epub 2021 Jun 25.

Engineering Research Center of High Value Utilization of Western China Fruit Resources, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, People's Republic of China.

Carbon nanoparticles (CNPs) extensively present in thermal-processed foods. Sodium nitrite (NaNO) and tea polyphenols (TP) are commonly used in meat processing, while the properties and cytotoxicity of CNPs existed in fried pork added NaNO and TP remain unknown. The results showed that compared with no addition (NA, 4.008 ± 0.43 nm) in soaked pork, the smaller diameters of CNPs (0.968 ± 0.44 nm) were found in CNPs-NaNO-20 group (addition 20 mg/kg NaNO), the larger (155.8 ± 7.30 nm) in CNPs-TP-100 group (addition 100 mg/kg TP). The diameter of CNPs was positively correlated with the added concentration. CNPs decreased the viability of HL-7702 cells. Compared with NA group, cell viability in CNPs-NaNO-80 group was obviously (p < 0.05) decreased by 3.17%, while the CNPs-TP-200 group was 13.84% higher. CNPs could block cells growth by arresting cells in S-phase and increasing cellular ROS levels. CNPs generated in fired pork added 200 mg/kg TP in soaking showed less cytotoxicity.
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http://dx.doi.org/10.1016/j.foodchem.2021.130464DOI Listing
June 2021

Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification.

J Ethnopharmacol 2021 Jul 8;279:114399. Epub 2021 Jul 8.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Dendrobium chrysotoxum Lindl, a well-known traditional Chinese medicinal herb used in the treatment of gastric disease, is distinguished as the first of the "nine immortal grasses". Dendrobium chrysotoxum Lindl and the traditional Chinese medicine prescriptions containing Dendrobium chrysotoxum Lindl are often prescribed clinically to treat chronic gastritis and precancerous lesions of gastric cancer (PLGC), showing favorable clinical effects and medicinal value in the prevention of gastric cancer. However, the effective ingredients and pharmacological mechanisms through which Dendrobium chrysotoxum Lindl prevents and treats PLGC have not been adequately identified or interpreted.

Aim Of The Study: The present study aimed to evaluate the effective ingredients and pharmacological mechanisms of Dendrobium chrysotoxum Lindl in the prevention and treatment of PLGC using network pharmacology. In addition, in vitro verification was performed to evaluate the mechanism of action of Erianin, the main active ingredient in Dendrobium chrysotoxum Lindl, providing experimental evidence for the clinical use of Dendrobium chrysotoxum Lindl in the treatment of PLGC.

Materials And Methods: Using network pharmacology methods, the main ingredients in Dendrobium chrysotoxum Lindl were screened from the ETCM, BATMAN-TCM, and TCMID databases, and their potential targets were predicted using the Swiss Target Prediction platform. The targets related to PLGC were retrieved through the GeneCard database, and the targets common to the main ingredients of Dendrobium chrysotoxum Lindl and PLGC were analyzed. The protein-protein interaction (PPI) network was obtained via the STRING database and analyzed visually using Cytoscape 3.7.2. The underlying mechanisms of the common targets identified through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were analyzed using DAVID online. The "component-target-pathway" networks of Dendrobium chrysotoxum Lindl and Erianin were visually constructed by Cytoscape 3.7.2. The biological activity evaluation of Erianin's effect on PLGC was carried out using MC cell lines, the PLGC cell model established using MNNG to induce damage in normal gastric mucosal epithelial cell (GES-1). After the intervention of different concentrations of Erianin, MC cell viability was explored using the MTT assays, cell migration was determined by wound healing assays, the cell cycle and apoptosis were analyzed using flow cytometry, and the expression levels of related proteins and their phosphorylation in the HRAS-PI3K-AKT signaling pathway were detected by Western blot.

Results: The "component-target-pathway" network constructed in this study showed 37 active ingredients from Dendrobium chrysotoxum Lindl and 142 overlapping targets related to both Dendrobium chrysotoxum Lindl and PLGC. The targets were associated with a variety of cancer-related signaling pathways, including Pathways in cancer, PI3K-Akt signaling pathway, Rap1 signaling pathway, Focal adhesion, Ras signaling pathway, and MAPK signaling pathway. Notably, the network showed that Erianin, the primary active ingredient from Dendrobium chrysotoxum Lindl and the component associated with the most targets, could regulate Pathways in cancer, PI3K-AKT signaling pathway, Focal adhesion, Rap1 signaling pathway, cell cycle, and RAS signaling pathway in the treatment of PLGC. Verification through in vitro experiments found that Erianin can significantly inhibit MC cell viability, inhibit cell migration, block the cell cycle in the G2/M phase, and induce cell apoptosis in a dose-dependent manner. The results of the Western blot experiment further showed that Erianin can significantly decrease the protein expression levels of HRAS, AKT, p-AKT, MDM2, Cyclin D1, and p-Gsk3β, and increase the protein expression level of p21, which suggests that Erianin can treat PLGC by regulating the HRAS-PI3K-AKT signaling pathway.

Conclusion: This study explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with Dendrobium chrysotoxum Lindl in the treatment of PLGC. Our results suggest that Erianin may be a promising candidate in the development of prevention and treatment methods for PLGC. This study provided experimental evidence for the clinical use of Dendrobium chrysotoxum Lindl to treat PLGC and prevent gastric cancer.
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http://dx.doi.org/10.1016/j.jep.2021.114399DOI Listing
July 2021

Perturbations in nitric oxide homeostasis promote Arabidopsis disease susceptibility towards Phytophthora parasitica.

Mol Plant Pathol 2021 Jul 9. Epub 2021 Jul 9.

The Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Phytophthora species can infect hundreds of different plants, including many important crops, causing a number of agriculturally relevant diseases. A key feature of attempted pathogen infection is the rapid production of the redox active molecule nitric oxide (NO). However, the potential role(s) of NO in plant resistance against Phytophthora is relatively unexplored. Here we show that the level of NO accumulation is crucial for basal resistance in Arabidopsis against Phytophthora parasitica. Counterintuitively, both relatively low or relatively high NO accumulation leads to reduced resistance against P. parasitica. S-nitrosylation, the addition of a NO group to a protein cysteine thiol to form an S-nitrosothiol, is an important route for NO bioactivity and this process is regulated predominantly by S-nitrosoglutathione reductase 1 (GSNOR1). Loss-of-function mutations in GSNOR1 disable both salicylic acid accumulation and associated signalling, and also the production of reactive oxygen species, leading to susceptibility towards P. parasitica. Significantly, we also demonstrate that secreted proteins from P. parasitica can inhibit Arabidopsis GSNOR1 activity.
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http://dx.doi.org/10.1111/mpp.13102DOI Listing
July 2021

Thermal Dynamics of Charge Density Wave Pinning in ZrTe_{3}.

Phys Rev Lett 2021 Jun;126(25):256401

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Impurity pinning has long been discussed to have a profound effect on the dynamics of an incommensurate charge density wave (CDW), which would otherwise slide through the lattice without resistance. Here, we visualize the impurity pinning evolution of the CDW in ZrTe_{3} using the variable temperature scanning tunneling microscopy. At low temperatures, we observe a quasi-1D incommensurate CDW modulation moderately correlated to the impurity positions, indicating a weak impurity pinning. As we raise the sample temperature, the CDW modulation gets progressively weakened and distorted, while the correlation with the impurities becomes stronger. Above the CDW transition temperature, short-range modulations persist with the phase almost all pinned by impurities. The evolution from weak to strong impurity pinning through the CDW transition can be understood as a result of losing phase rigidity.
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http://dx.doi.org/10.1103/PhysRevLett.126.256401DOI Listing
June 2021

MT1-MMP-dependent ECM processing regulates laminB1 stability and mediates replication fork restart.

PLoS One 2021 8;16(7):e0253062. Epub 2021 Jul 8.

Department of Dermatology, University of Miami Miller School of Medicine, Miami, FL, United States of America.

Radiotherapy remains a mainstay of treatment for a majority of cancer patients. We have previously shown that the membrane bound matrix metalloproteinase MT1-MMP confers radio- and chemotherapy resistance to breast cancer via processing of the ECM and activation of integrinβ1/FAK signaling. Here, we further discovered that the nuclear envelope protein laminB1 is a potential target of integrinβ1/FAK. FAK interacts with laminB1 contributing to its stability. Stable laminB1 is found at replication forks (RFs) where it is likely to allow the proper positioning of RF protection factors, thus preventing RF degradation. Indeed, restoration of laminB1 expression rescues replication fork stalling and collapse that occurs upon MT1-MMP inhibition, and reduces DNA damage in breast cancer cells. Together, these data highlight a novel mechanism of laminB1 stability and replication fork restart via MT1-MMP dependent extracelluar matrix remodeling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253062PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266045PMC
July 2021
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