Publications by authors named "Jing Qian"

461 Publications

Keratinocyte membrane-mediated nanodelivery system with dissolving microneedles for targeted therapy of skin diseases.

Biomaterials 2021 Sep 23;278:121142. Epub 2021 Sep 23.

Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

There is a lack of actively targeting drug delivery carriers for the topical treatment of epidermal diseases, which results in drug waste and an increased incidence of toxic side effects in the clinic. We recently discovered that epidermal cells (HaCaT cells) have homologous targeting functions and developed HaCaT cell membrane-coated pH-sensitive micelles for therapeutic active targeting of skin disease. We encapsulated shikonin in these biomimetic nanocarriers and found that the nanocarriers accumulated mainly in the active epidermis when delivered with karaya gum-fabricated water-soluble microneedles. The nanocarriers were internalized by the target cells, resulting in swelling of histidine fragments with protonation and subsequent triggering of drug release, which increased the therapeutic efficacy of shikonin against imiquimod-induced psoriatic epidermal hyperplasia. This emerging biomimetic delivery strategy is a new approach for improving the treatment of skin diseases and is also very promising for use in the field of cosmetics. Additionally, we found abnormally high protein expression of Na/K-ATPase in diseased skin; thus, this protein may be a biomarker of psoriasis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121142DOI Listing
September 2021

Corrigendum: My Fault? Coworker Incivility and Organizational Citizenship Behavior: The Moderating Role of Attribution Orientation on State Guilt.

Front Psychol 2021 30;12:741067. Epub 2021 Aug 30.

Business School, Beijing Normal University, Beijing, China.

[This corrects the article DOI: 10.3389/fpsyg.2021.683843.].
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http://dx.doi.org/10.3389/fpsyg.2021.741067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435898PMC
August 2021

Sodium tanshinone IIA sulfonate attenuates cigarette smoke extract-induced mitochondrial dysfunction, oxidative stress and apoptosis in alveolar epithelial cells by enhancing SIRT1 pathway.

Toxicol Sci 2021 Sep 13. Epub 2021 Sep 13.

State Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Emphysema is one of the most important phenotypes for chronic obstructive pulmonary disease (COPD). Apoptosis in alveolar epithelial cells (AECs) causes the emphysematous alterations in the smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to attenuate mitochondrial dysfunction, oxidative stress, and to modulate apoptosis. It has been shown that sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, protects against cigarette smoke (CS)-induced emphysema/COPD in mice. However, the mechanisms underlying these findings remain unclear. Here, we investigate whether and how STS attenuates on AEC apoptosis via a SIRT1-dependent mechanism. We found that STS treatment decreased CS extract (CSE)-induced apoptosis in human alveolar epithelial A549 cells. STS reduced oxidative stress, improved mitochondrial function and mitochondrial membrane potential (ΔΨm), and restored mitochondrial dynamics-related protein expression. Moreover, STS promoted mitophagy, and increased oxidative phosphorylation (OXPHOS) protein levels (Complexes I-IV) in CSE-stimulated A549 cells. The protective effects of STS were associated with SIRT1 upregulation, since SIRT1 inhibition by EX 527 significantly attenuated or abolished the ability of STS to reverse the CSE-induced mitochondrial damage, oxidative stress, and apoptosis in A549 cells. In conclusion, STS ameliorates CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. These findings provide novel mechanisms underlying the protection of STS against CS-induced COPD.
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http://dx.doi.org/10.1093/toxsci/kfab087DOI Listing
September 2021

Controlling the ligands of CdZnTe quantum dots to design a super simple ratiometric fluorescence nanosensor for silver ion detection.

Analyst 2021 Sep 13;146(18):5747-5755. Epub 2021 Sep 13.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.

A super simple ratiometric fluorescence nanosensor has been fabricated by controlling the ligands of CdZnTe quantum dots (QDs), allowing the sensitive and visual detection of silver ions (Ag). The green-emitting L-cysteine-protected CdZnTe QDs (Lcys-CdZnTe QDs) had a specific response to Ag and were used as the reporting probe, while the red-emitting -acetyl-L-cysteine-protected CdZnTe QDs (NAC-CdZnTe QDs) showed no obvious response to all tested metal ions and were selected as the reference probe. Simply mixing them without any encapsulated synthesis ultimately produced a time-saving, low-cost detection method, allowing the sensitive and visual detection of Ag in samples. The proposed nanosensor exhibited a linear range of 0.5-4.0 μM along with a detection limit of 0.17 μM, and has been successfully applied in real tap water and lake water samples. This nanosensor also showed obvious color changes in the detection process and has potential in visual semi-quantitative detection. Our approach may provide a general and feasible strategy for designing ratiometric fluorescence nanosensors, which will attract a wide range of interest in sensing-related fields.
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http://dx.doi.org/10.1039/d1an01200bDOI Listing
September 2021

Novel Anti-Interference Strategy for a Self-Powered Sensor: Mediator-Free and Biospecific Photocathode Interface.

Anal Chem 2021 Sep 10;93(37):12690-12697. Epub 2021 Sep 10.

Key Laboratory of Modern Agriculture Equipment and Technology, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.

As a new electrochemical sensing concept, a self-powered sensor shows a good application prospect in the field of analysis. However, it is still a great challenge to improve the anti-interference capability of sensors through reasonable design. In this study, we investigated the difference between the single photoanode and photocathode self-powered sensor and combined the advantages of these two aspects to fabricate a mediator-free self-powered aptasensor based on the dual-photoelectrode system, which combined the biological events from the photocathode. The biological events occurred at the photocathode could avoid the interference caused by the generated hole oxidation of reducing small molecules in the real sample on the photoanode surface, which was helpful to enhance the anti-interference capability of the sensor. Moreover, due to the sufficient Fermi level differentiation between two photoelectrodes, the redox mediator was not necessary. This could avoid the redox reaction caused by the introduction of extra electron donors or electron acceptors occurring before the photoelectrical behavior, thus improving the accuracy of the sensor. According to the influence of the generated biological conjugate on the external circuit, electron transmission between interfaces, and the obstruction of visible light irradiation, the sensitive and accurate detection of the analytical model was achieved. This work provided a proof-of-concept for the establishment of a mediator-free dual-photoelectrode self-powered sensing platform with high sensitivity and strong anti-interference performance.
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http://dx.doi.org/10.1021/acs.analchem.1c02555DOI Listing
September 2021

Mechanistic process understanding of the self-assembling behaviour of asymmetric bolaamphiphilic short-peptides and their templating for silica and titania nanomaterials.

Nanoscale 2021 Aug 27;13(31):13318-13327. Epub 2021 Jul 27.

Centre for Bioengineering and Biotechnology, China University of Petroleum, Qingdao 266580, China.

Investigation of the self-assembly of peptides is critically important to clarify certain biophysical phenomena, fulfill some biological functions, and construct functional materials. However, it is still a challenge to precisely predict the self-assembled structures of peptides because of their complicated driving forces and various assembling pathways. In this work, to elucidate the effects of noncovalent interactions including hydrogen bonding, molecular geometry, and hydrophobic and electrostatic interactions on the peptide self-assembly, a series of asymmetric bolaamphiphilic short peptides consisting of Ac-EIK-NH (EIK), Ac-EIK-NH (EIK), Ac-KIE-NH (KIE) and Ac-KIE-NH (KIE) were designed and their self-assembling behaviors at different solution pH values were investigated systematically. The peptides self-assembled into twisted nanofibers under most conditions except for EIK in a strongly alkaline solution and KIE under a strongly acidic condition, in which they self-assembled into nanotubes via helical monolayer nanosheet intermediates. In particular, KIE nanotubes are formed under acidic conditions, and its diameters are ∼500 nm much greater than most of the self-assembled structures from bolaamphiphilic peptides. Moreover, reversible morphological transition between the nanotubes and twisted nanofibers was observed with the change in solution pH. Such tunable self-assembled structures and switchable surface properties of the asymmetric bolaamphiphilic short-peptides allow them to be used as templates to construct advanced materials. Silica and titania nanomaterials faithful to the peptide templates in morphology were prepared at ambient temperature. This work clearly elucidates the effects of noncovalent interactions on the peptide self-assembly and also provides new insights into the design and preparation of complicated inorganic materials from tunable organic templates.
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http://dx.doi.org/10.1039/d1nr01661jDOI Listing
August 2021

Understanding the link between obesity and severe COVID-19 outcomes: Causal mediation by systemic inflammatory response.

J Clin Endocrinol Metab 2021 Sep 2. Epub 2021 Sep 2.

Division of Cardiology, Columbia University, New York, NY USA.

Background: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.

Objective: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes.

Design: Hospital-based, observational.

Setting: Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/NewYork-Presbyterian Hospital (CUIMC/NYP).

Patients Or Other Participants: N=3828 SARS-CoV-2-infected patients hospitalized February to May 2020.

Main Outcome Measures: Mediation analysis is used to evaluate whether peak inflammatory biomarkers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, ferritin, white blood cell count and interleukin-6] are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care.

Results: In the MGH cohort (n=1202), obesity was associated with greater likelihood of ventilation or death [OR=1.73, 95% CI=(1.25, 2.41), p=0.001] and higher peak CRP (p<0.001) compared to non-obese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (p<0.001). Evidence of mediation was more pronounced in patients <65 years [proportion mediated=0.52 (p<0.001) versus 0.44 (p=0.180)]. Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n=2626).

Conclusions: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients <65 years, captured by CRP and ESR. Contextualized in clinical trials findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
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http://dx.doi.org/10.1210/clinem/dgab629DOI Listing
September 2021

Ferris wheel patterning of Rydberg atoms using electromagnetically induced transparency with optical vortex fields.

Opt Lett 2021 Sep;46(17):4204-4207

We study the formation of spatially dependent electromagnetically induced transparency (EIT) patterns from pairs of Laguerre-Gauss (LG) modes in an ensemble of cold interacting Rydberg atoms. The EIT patterns can be generated when two-photon detuning does not compensate for the Rydberg level energy shift induced by van der Waals interaction. Depending on the topological numbers of each LG mode, we can pattern dark and bright Ferris-wheel-like structures in the absorption profile with tunable barriers between sites, providing confinement of Rydberg atoms in transverse direction while rendering them transparent to light at specific angular positions. We also show how the atomic density may affect the azimuthal modulation of the absorption profile.
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http://dx.doi.org/10.1364/OL.427000DOI Listing
September 2021

Brucella melitensis UGPase inhibits the activation of NF-κB by modulating the ubiquitination of NEMO.

BMC Vet Res 2021 Aug 30;17(1):289. Epub 2021 Aug 30.

State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, 130112, Changchun, China.

Background: UTP-glucose-1-phosphoryl transferase (UGPase) catalyzes the synthesis of UDP-glucose, which is essential for generating the glycogen needed for the synthesis of bacterial lipopolysaccharide (LPS) and capsular polysaccharide, which play important roles in bacterial virulence. However, the molecular function of UGPase in Brucella is still unknown.

Results: In this study, the ubiquitination modification of host immune-related protein in cells infected with UGPase-deleted or wild-type Brucella was analyzed using ubiquitination proteomics technology. The ubiquitination modification level and type of NF-κB Essential Modulator (NEMO or Ikbkg), a molecule necessary for NF-κB signal activation, was evaluated using Coimmunoprecipitation, Western blot, and dual-Luciferase Assay. We found 80 ubiquitin proteins were upregulated and 203 ubiquitin proteins were downregulated in cells infected with B. melitensis 16 M compared with those of B. melitensis UGPase-deleted strain (16 M-UGPase). Moreover, the ubiquitin-modified proteins were mostly enriched in the categories of regulation of kinase/NF-κB signaling and response to a bacterium, suggesting Brucella UGPase inhibits ubiquitin modification of related proteins in the host NF-κB signaling pathway. Further analysis showed that the ubiquitination levels of NEMO K63 (K63-Ub) and Met1 (Met1-Ub) were significantly increased in the 16 M-UGPase-infected cells compared with that of the 16 M-infected cells, further confirming that the ubiquitination levels of NF-κB signaling-related proteins were regulated by the bacterial UGPase. Besides, the expression level of IκBα was decreased, but the level of p-P65 was significantly increased in the 16 M-UGPase-infected cells compared with that of the 16 M- and mock-infected cells, demonstrating that B. melitensis UGPase can significantly inhibit the degradation of IκBα and the phosphorylation of p65, and thus suppressing the NF-κB pathway.

Conclusions: The results of this study showed that Brucella melitensis UGPase inhibits the activation of NF-κB by modulating the ubiquitination of NEMO, which will provide a new scientific basis for the study of immune mechanisms induced by Brucella.
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http://dx.doi.org/10.1186/s12917-021-02993-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404259PMC
August 2021

Salidroside alleviates taurolithocholic acid 3-sulfate-induced AR42J cell injury.

Biomed Pharmacother 2021 Oct 21;142:112062. Epub 2021 Aug 21.

Laboratory Animal Center of Nantong University, Nantong 226001, Jiangsu, China. Electronic address:

Objectives: To investigate the protective effects of Salidroside (Sal) on AP cell model induced by taurolithocholic acid 3-sulfate (TLC-S) as well as its underlying mechanism.

Methods: AR42J cells were divided into normal group (N group), AP cell model group (Mod group), Sal treated alone group (S+N group) and Sal treated AP cell model group (S+Mod group). The cell viability was examined by CCK-8 assay. Secretion of lipase and trypsin by AR42J cells, quantified using commercial assay kits, was used as the markers of TLC-S-induced pancreatitis. The levels of TNF-α, IL-1β, IL-8, IL-6 and IL-10 in the cell supernatant were measured by ELISA. The effect of Sal on molecules in the NF-κB signaling pathway and autophagy was investigated by qRT-PCR and western blot.

Results: The decreased cell viability in Mod group was increased by Sal (P < 0.01). The upheaved activities of lipase and trypsin in AP cell model were declined by Sal (P < 0.01). The levels of TNF-α, IL-1β, IL-8 and IL-6 in the cell supernatant, Beclin-1 and LC3-Ⅱ mRNA and protein, p-p65/p65 protein, which were increased in AP cell model, were decreased by Sal; and IL-10 in the cell supernatant, LAMP2 mRNA and protein, p-IκBα/IκBα protein which was declined in AP cell model, was increased by Sal (P < 0.05 or 0.01). There were no significant differences in all indexes between the N and S+N groups (P > 0.05).

Conclusions: Sal alleviated AR42J cells injury induced by TLC-S, inhibited the inflammatory responses and modulated the autophagy, mainly through inhibiting the NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.biopha.2021.112062DOI Listing
October 2021

Lentogenic NDV V protein inhibits IFN responses and represses cell apoptosis.

Vet Microbiol 2021 Oct 8;261:109181. Epub 2021 Jul 8.

College of Veterinary Medicine, College of Animal Science, Jilin University, Changchun, 130062, China; Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, 130122, China. Electronic address:

The V protein of Newcastle disease virus (NDV) has been shown to inhibit the secretion of interferon (IFN) during infection, which is responsible for the promotion of NDV pathogenicity. However, the ability of the V protein to suppress host innate immunity is not well understood. In this study, we explored the function of V protein and its relationship with virulence by generating V protein-inserted recombinant (r) NDVs. Using rNDVs as a model, we examined the efficiency of infection, IFN responses, and apoptosis of host cells during infection. We found that viral propagation occurred smoothly when V protein from lentogenic NDV is inserted instead of the V protein from the velogenic strain. The infection of lentogenic V protein-inserted rNDV induced less expression of IFNs and downstream antiviral proteins via efficient degradation of p-STAT1 and MDA5. Moreover, velogenic V protein triggered a higher apoptosis rate during infection thereby restricting the replication of NDV. Conversely, lentogenic V protein inhibits IFN responses efficiently and induces less apoptosis compared to the velogenic strain. Our findings provide a novel understanding of the role of V protein in NDV pathogenicity.
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http://dx.doi.org/10.1016/j.vetmic.2021.109181DOI Listing
October 2021

Nonparametric estimation of the survival distribution under covariate-induced dependent truncation.

Biometrics 2021 Aug 13. Epub 2021 Aug 13.

Department of Biostatistics, School of Global Public Health, New York University, New York, New York, USA.

There is often delayed entry into observational studies, which results in left truncation. In the estimation of the distribution of time-to-event from left-truncated data, standard survival analysis methods require quasi-independence between the truncation time and event time. Incorrectly assuming quasi-independence may lead to biased estimation. We address the problem of estimation of the survival distribution when dependence between the event time and its left truncation time is induced by shared covariates. We introduce propensity scores for truncated data and propose two inverse probability weighting methods that adjust for both truncation and dependence, if all of the shared covariates are measured. The proposed methods additionally allow for right censoring. We evaluate the proposed methods in simulations, conduct sensitivity analyses, and provide guidelines for use in practice. We illustrate our approach in application to data from a central nervous system lymphoma study. The proposed methods are implemented in the R package, depLT.
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http://dx.doi.org/10.1111/biom.13545DOI Listing
August 2021

Anlotinib Combined with Cranial Radiotherapy for Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospectively, Control Study.

Cancer Manag Res 2021 4;13:6101-6111. Epub 2021 Aug 4.

The First Affiliated Hospital of Bengbu Medical College & Tumor Hospital Affiliated to Bengbu Medical College, Bengbu, 233004, People's Republic of China.

Introduction: Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear.

Methods: We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models.

Results: This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups ( > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27-0.95; = 0.04), and age ≥57 years (HR 1.04, 95% CI 1.01-1.08, = 0.014) and KPS score ≤80 (HR 1.04, 95% CI 1.01-1.08, = 0.014) were independent disadvantage predictors of OS ( < 0.05). In addition, although this difference was not statistically significant ( > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT.

Conclusion: Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.
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http://dx.doi.org/10.2147/CMAR.S319650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349551PMC
August 2021

A smart material built upon the photo-thermochromic effect and its use for managing indoor temperature.

Chem Commun (Camb) 2021 Sep 9;57(69):8628-8631. Epub 2021 Aug 9.

School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China.

We demonstrate a material by dispersing a thermochromic mixture of leuco dye, developer, and solvent as microspheres in a polymer matrix to improve the efficiency of building energy management. The smart, photo-thermochromic film can automatically switch between a colored and colorless state in response to climate temperature and light to realize photothermal heating and cooling.
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http://dx.doi.org/10.1039/d1cc03379dDOI Listing
September 2021

Sorption of organochlorine pesticides on polyethylene microplastics in soil suspension.

Ecotoxicol Environ Saf 2021 Oct 5;223:112591. Epub 2021 Aug 5.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

As a new type of environmental pollutant, microplastics (MPs) can adsorb residual organochlorine pesticides (OCPs) in the soil and pose a severe threat to the soil ecosystems. To understand the interaction between soil MPs and OCPs, the sorption of two kinds of OCPs, including hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs), on polyethylene (PE) microplastics in soil suspension was studied through sorption kinetics and isotherm models. The effects of solution/soil ratio and MPs diameter on sorption were examined. The kinetic experiment results show that the sorption equilibrium was 12 h, and the sorption process of OCPs on MPs can be well described by a pseudo-second-order model. The Freundlich model (R = 0.942-0.997) provides a better fit to the sorption isotherm data than the Langmuir model (R = 0.062-0.634), indicating that the sorption process takes place on the nonuniform surface of MPs. The MPs had a good sorption effect on OCPs when the solution/soil ratio was from 75:1 to 100:1. As the diameter of MPs increases, the sorption capacity decreases. These results provide support for further research on microplastic pollution in soil.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112591DOI Listing
October 2021

A Three-Dimensional Micromixer Using Oblique Embedded Ridges.

Micromachines (Basel) 2021 Jul 8;12(7). Epub 2021 Jul 8.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

A micromixer is one of the most significant components in a microfluidic system. A three-dimensional micromixer was developed with advantages of high efficiency, simple fabrication, easy integration, and ease of mass production. The designed principle is based on the concepts of splitting-recombination and chaotic advection. A numerical model of this micromixer was established to characterize the mixing performance for different parameters. A critical Reynolds number (Re) was obtained from the simulation results. When the Re number is smaller than the critical value, the fluid mixing is mainly dependent on the mechanism of splitting-recombination, therefore, the length of the channel capable of complete mixing (complete mixing length) increases as the Re number increases. When the Re number is larger than the critical value, the fluid mixing is dominated by chaotic advection, and the complete mixing length decreases as the Re number increases. For normal fluids, a complete mixing length of 500 µm can be achieved at a very small Re number of 0.007 and increases to 2400 µm as the Re number increases to the critical value of 4.7. As the Re number keep increasing and passes the critical Re number, the complete mixing length continues to descend to 650 µm at the Re number of 66.7. For hard-to-mix fluids (generally referring to fluids with high viscosity and low diffusion coefficient, which are difficult to mix), even though no evidence of strong chaotic advection is presented in the simulation, the micromixer can still achieve a complete mixing length of 2550 µm. The mixing performance of the micromixer was also verified by experiments. The experimental results showed a consistent trend with the numerical simulation results, which both climb upward when the Re number is around 0.007 (flow rate of 0.03 μm/min) to around 10 (flow rate of 50 μm/min), then descend when the Re number is around 13.3 (flow rate of 60 µm/min).
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http://dx.doi.org/10.3390/mi12070806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305879PMC
July 2021

Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

Med Sci Monit 2021 Jul 31;27:e929474. Epub 2021 Jul 31.

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China (mainland).

BACKGROUND The impact of therapeutic drug management (TDM) on reducing toxicity and improving efficacy in colorectal cancer (CRC) patients receiving fluorouracil-based chemotherapy is still unclear. MATERIAL AND METHODS A total of 207 patients (Study Group n=54, Historical Group n=153) with metastatic colorectal cancer were enrolled. All of them received 6 administrations of the 5-FU based regimens. Initial 5-FU dosing of all patients was calculated using body surface area (BSA). In the Study Group, individual exposure during each cycle was measured using a nanoparticle immunoassay, and the 5-FU blood concentration was calculated using the area under the curve (AUC). We adjusted the 5-FU infusion dose of the next cycle based on the AUC data of the previous cycle to achieve the target of 20-30 mg×h/L. RESULTS In the fourth cycle, patients in the target concentration range (AUC mean, 26.3 mg×h/L; Median, 28 mg×h/L; Range, 14-38 mg×h/L; CV, 22.4%) accounted for 46.8% of all patients, which were more than the ones in the first cycle (P<0.001). 5-FU TDM significantly reduced the toxicity of chemotherapy and improved its efficacy. The Study Group (30/289) showed a lower percentage of severe adverse events than that in the Historical Group (185/447) (P<0.001). The incidences of complete response and partial response in the Study Group were higher than those in the Historical Group (P=0.032). CONCLUSIONS TDM in colorectal cancer can reduce toxicity, improve efficacy and clinical outcome, and can be routinely used in 5-FU-based chemotherapy.
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http://dx.doi.org/10.12659/MSM.929474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336255PMC
July 2021

Characterization of the structural and dynamic changes of cell wall obtained by ultrasound-water and ultrasound-alkali treatments.

Ultrason Sonochem 2021 Sep 18;77:105672. Epub 2021 Jul 18.

Beijing Key Laboratory of Wood Science and Engineering, College of Material Science and Technology, Beijing Forestry University, No. 35 Tsinghua East Road Haidian District, Beijing, PR China. Electronic address:

It is well-known that ultrasound has been studied for its cavitation, mechanical and thermal effects. As a pretreatment technology, ultrasonic alkali treatment has attracted much attention in the field of biomass biochemical transformation. In this study, the structural and dynamic changes of wood cell walls during ultrasound-water, alkali, and ultrasound-alkali treatments were investigated by stereoscopic microscopy, confocal Raman microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The results indicated that the ultrasound-water, alkali, and ultrasound-alkali treatments had the effect of removing extractives from conduits. The uniform self-shrinking samples with shrinkage conduits were obtained by the alkali and ultrasound-alkali treatments. All of the treatments affected the relative content, structure and distribution of the chemical components in the wood cell walls. Compared with water-immersion samples, the relative content of hemicellulose of the treated samples reduced from 32.31% to 7.02% for ultrasound-8% NaOH treated samples. For the signal intensity of lignin, ultrasound-water treated and ultrasound-alkali treated samples displayed a more significant reductions than the alkali treated samples in the cell wall region. The crystal zone and amorphous zone of cellulose coexisted before and after the treatment, for all of the treated samples, and particularly for the ultrasound-assisted treated samples, the crystallinity increased from 38.15% for water-immersion samples to 57.42% for ultrasound-8% NaOH treated samples.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339218PMC
September 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

My Fault? Coworker Incivility and Organizational Citizenship Behavior: The Moderating Role of Attribution Orientation on State Guilt.

Front Psychol 2021 1;12:683843. Epub 2021 Jul 1.

Business School, Beijing Normal University, Beijing, China.

The effect of workplace incivility on the behavior of individuals has been a widespread concern in recent years. Previous studies have largely linked uncivilized workplaces to discrete emotions such as anger and frustration, as well as negative behaviors such as withdrawal and aggression. However, few studies have focused on the specific role of introverted discrete emotions (i.e., guilt). At the same time, the role of individual differences (i.e., attribution orientation) has not been paid enough attention. Based on the attribution theory, this study examines how coworker incivility influences the organizational citizenship behavior (OCB) of individuals and the moderating role of internal attribution orientation on this process. Using the data of 109 employees for 10 consecutive working days as samples, we employed the PROCESS macro and MPLUS to examine our hypotheses. The results indicated that coworker incivility experience was positively related to the state guilt of employees only when they were high in internal attribution orientation rather than low. State guilt, in turn, was positively related to their OCB. This study expands the research of emotional response to uncivilized experience and provides a new perspective to understand the relationship between workplace incivility and potential positive outcomes. The implications of the general findings are discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.683843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282195PMC
July 2021

Nonsurgical Treatment for Congenital Auricular Deformities: A Systematic Review and Meta-analysis.

Aesthetic Plast Surg 2021 Jul 6. Epub 2021 Jul 6.

Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The effectiveness and safety of non-surgical correction for congenital auricular deformities (CADs) remain unclear owing to a lack of high-level evidence. This systematic review and meta-analysis aimed to estimate the overall success and complication rates of the non-surgical correction for CAD.

Methods: We searched PubMed, Medline, and Cochrane Library for eligible studies. The pooled success and complication rates of non-surgical correction were estimated using a random effects model. Subgroup analyses were performed to compare the success rates between patients treated with splints and molding systems, between those younger and older than 6-weeks, and among those with different types of CADs.

Results: The review yielded 14 studies. The pooled success rate of non-surgical treatment was 93% (95% CI: 88%-97%). The success rates with splints and commercialized molding systems were 94% and 92%, respectively. The success rate was higher if non-surgical correction was initiated before age 6 weeks (96% vs. 82%). Prominent ears showed a lower success rate (85%) than other types of CADs (all > 90%). The pooled complication rate was 18% (95% CI: 10%-29%). Complications, including skin wound, irritation, and rash, were mild and easily treatable.

Conclusion: The non-surgical correction of CADs is highly effective and safe. Splints and molding systems offer similar effectiveness. Non-surgical correction is more beneficial if applied within 6 weeks of birth. Prominent ears have a lower, but still acceptable, success rate compared to other types of CAD. We recommend the early use of non-surgical correction to achieve favorable outcomes.

Level Of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02427-9DOI Listing
July 2021

How to design, fabricate, and validate a customized COMS-style eye plaque: Illustrated with a narrow-slotted plaque example.

Brachytherapy 2021 Jun 30. Epub 2021 Jun 30.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN.

Purpose: A customized Collaborative Ocular Melanoma Study (COMS)-style eye plaque may provide superior dosimetric coverage compared with standard models for certain intraocular tumor locations and shapes. This work provides a recipe for developing and validating such customized plaques.

Methods And Materials: The concept-into-clinical treatment process for a customized COMS-style eye plaque begins with a CAD model design that meets the specifications of the radiation oncologist and surgeon based on magnetic resonance, ultrasound, and clinical measurements, as well as a TG-43 hybrid heterogeneity-corrected dose prediction to model the dose distribution. Next, a 3D printed plastic prototype is created and reviewed. After design approval, a Modulay plaque is commercially fabricated. Quality assurance (QA) is subsequently performed to verify the physical measurements of the Modulay and Silastic and also includes dosimetric measurement of the calibration, depth dose, and dose profiles. Sterilization instructions are provided by the commercial fabricator. This customization procedure and QA methodology is demonstrated with a narrow-slotted plaque that was recently constructed for the treatment of a circumpapillary (e.g., surrounding the optic disk) ocular tumor.

Results: The production of a customized COMS-style eye plaque is a multistep process. Dosimetric modeling is recommended to ensure that the design will meet the patient's needs, and QA is essential to confirm that the plaque has the proper dimensions and dose distribution. The customized narrow-slotted plaque presented herein was successfully implemented in the clinic, and provided superior dose coverage of juxtapapillary and circumpapillary tumors compared with standard or notched COMS-style plaques. Plaque development required approximately 30 h of physicist time and a fabrication cost of $1500.

Conclusion: Customized eye plaques may be used to treat intraocular tumors that cannot be adequately managed with standard models. The procedure by which a customized COMS-style plaque may be designed, fabricated, and validated was presented along with a clinical example.
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http://dx.doi.org/10.1016/j.brachy.2021.04.001DOI Listing
June 2021

Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation.

Cell Rep 2021 Jun;35(12):109272

Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address:

The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regulates retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) sensing-induced type I IFN signaling. Riok3 deficiency selectively inhibits RNA viral replication in vitro, resulting from an upregulated type I IFN pathway. Mice with myeloid-specific Riok3 knockout also show a more robust induction of type I IFN upon RNA virus infection and are more resistant to RNA virus-induced pathogenesis. Mechanistically, Riok3 recruits and interacts with the E3 ubiquitin ligase TRIM40, leading to the degradation of RIG-I and melanoma differentiation-associated gene-5 (MDA5) via K48- and K27-linked ubiquitination. Collectively, our data reveal the mechanism that Riok3 employs to be a negative regulator of antiviral innate immunity.
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http://dx.doi.org/10.1016/j.celrep.2021.109272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363743PMC
June 2021

Development of a Potent Antimicrobial Peptide With Photodynamic Activity.

Front Microbiol 2021 1;12:624465. Epub 2021 Jun 1.

College of Chemistry, Fuzhou University, Fuzhou, China.

The emergence of antibiotic-resistant bacteria poses a serious challenge to medical practice worldwide. A small peptide with sequence RWRWRW was previously identified as a core antimicrobial peptide with limited antimicrobial spectrum to bacteria, especially Gram-positive bacteria. By conjugating this peptide and its analogs with lipophilic phthalocyanine (Pc), we identified a new antibiotic peptide [PcGK(RW)]. The peptide demonstrates increased antimicrobial effect to both Gram-positive and Gram-negative . In addition, Pc also provides added and potent antimicrobial effect upon red light illumination. The inhibitory efficacy of PcGK(RW) was increased by ~140-fold to nanomolar range upon illumination. Moreover, PcGK(RW) was safe for mammalian cell and promoted wound healing in the mouse infection model. Our work provides a new direction to optimize antimicrobial peptides to enhance antimicrobial efficacy.
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http://dx.doi.org/10.3389/fmicb.2021.624465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203924PMC
June 2021

Closed bipolar electrode based fluorescence visualization biosensor for anti-interference detection of T-2 toxin.

Chem Commun (Camb) 2021 Jul;57(53):6511-6513

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, P. R. China. and Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

A closed bipolar electrode (BPE) based fluorescence visualization biosensor was successfully constructed and used for anti-interference detection of T-2 toxin.
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http://dx.doi.org/10.1039/d1cc02588kDOI Listing
July 2021

Rapid Potentiometric Detection of Chemical Oxygen Demand Using a Portable Self-Powered Sensor Chip.

Anal Chem 2021 06 8;93(24):8393-8398. Epub 2021 Jun 8.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.

Chemical oxygen demand (COD) is an important indicator of organic pollutants in water bodies. Most of the present testing methods have the disadvantages of having complicated steps, being time-consuming, and using toxic and hazardous substances. In this work, rapid potentiometric detection of chemical oxygen demand (COD) using a portable self-powered sensor chip was successfully developed. The indium tin oxide (ITO) electrode was etched by laser, and the photocatalytic materials TiO/CuS and Pt were modified onto the photoanode and the cathode to prepare the sensor chip. Based on the principle of photocatalytic degradation, organic pollutants can be oxidized by TiO/CuS, and the concentration will affect the generated voltage. The quantitative detection of COD in the range of 0.05-50 mg/L can be rapidly achieved within 5 min by a miniature device. Besides good portability and sensitivity, the proposed sensor also has the advantages of environmental friendliness and ease of use, which is an ideal choice for the on-site detection of water pollution.
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http://dx.doi.org/10.1021/acs.analchem.1c01863DOI Listing
June 2021

A ratiometric fluorescent sensor for rapid detection of the pyroglutamate aminopeptidase-1 in mouse tumors.

J Mater Chem B 2021 06;9(22):4546-4554

Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, P. R. China.

Pyroglutamate aminopeptidase-1 (PGP-1) is an important enzyme that plays an indispensable role in the process of inflammation. Up to now, few reports have been reported on the detection of PGP-1 activity in vivo and in vitro, and there are no reports on ratiometric detection. Here, the first red-emitting ratiometric fluorescent sensor (DP-1) for the specific detection of PGP-1 both in vivo and in vitro was designed and synthesized by using DCD-NH2 as the luminescent parent and pyroglutamate as a recognition group. After interacting with PGP-1, the amide bond is hydrolyzed by the enzyme and the color of the solution changes from yellow (λabs = 420 nm) to red (λabs = 520 nm), accompanied by obvious fluorescence emission wavelength change (from ∼564 nm to ∼616 nm). The probe has high specificity and sensitivity towards PGP-1 in about 10 min, and the DL is as low as 0.25 ng mL-1. Interestingly, under the stimulation of Freund's incomplete adjuvant and lipopolysaccharide, the imaging of DP-1 in HepG2 and RAW264 cells shows that the expression of PGP-1 is associated with inflammation. What's more, for the first, the imaging of a mouse tumor model confirms that the enzyme is closely related to the occurrence of some inflammation and tumor diseases. These results indicate that DP-1 can be used as an effective tool for real-time monitoring of PGP-1 levels both in vivo and in vitro and the study of inflammatory tumor pathology.
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http://dx.doi.org/10.1039/d1tb00372kDOI Listing
June 2021

Ultra-High Dose Rate FLASH Irradiation Induced Radio-Resistance of Normal Fibroblast Cells Can Be Enhanced by Hypoxia and Mitochondrial Dysfunction Resulting From Loss of Cytochrome C.

Front Cell Dev Biol 2021 30;9:672929. Epub 2021 Apr 30.

State Key Laboratory of Nuclear Physics and Technology, School of Physics and CAPT, Peking University, Beijing, China.

Ultra-high dose rate FLASH irradiation (FLASH-IR) has got extensive attention since it may provide better protection on normal tissues while maintain tumor killing effect compared with conventional dose rate irradiation. The FLASH-IR induced protection effect on normal tissues is exhibited as radio-resistance of the irradiated normal cells, and is suggested to be related to oxygen depletion. However, the detailed cell death profile and pathways are still unclear. Presently normal mouse embryonic fibroblast cells were FLASH irradiated (∼10 Gy/s) at the dose of ∼10-40 Gy in hypoxic and normoxic condition, with ultra-fast laser-generated particles. The early apoptosis, late apoptosis and necrosis of cells were detected and analyzed at 6, 12, and 24 h post FLASH-IR. The results showed that FLASH-IR induced significant early apoptosis, late apoptosis and necrosis in normal fibroblast cells, and the apoptosis level increased with time, in either hypoxic or normoxic conditions. In addition, the proportion of early apoptosis, late apoptosis and necrosis were significantly lower in hypoxia than that of normoxia, indicating that radio-resistance of normal fibroblast cells under FLASH-IR can be enhanced by hypoxia. To further investigate the apoptosis related profile and potential pathways, mitochondria dysfunction cells resulting from loss of cytochrome c (cyt c) were also irradiated. The results showed that compared with irradiated normal cells (cyt c), the late apoptosis and necrosis but not early apoptosis proportions of irradiated cyt c cells were significant decreased in both hypoxia and normoxia, indicating mitochondrial dysfunction increased radio-resistance of FLASH irradiated cells. Taken together, to our limited knowledge, this is the first report shedding light on the death profile and pathway of normal and cyt c cells under FLASH-IR in hypoxic and normoxic circumstances, which might help us improve the understanding of the FLASH-IR induced protection effect in normal cells, and thus might potentially help to optimize the future clinical FLASH treatment.
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http://dx.doi.org/10.3389/fcell.2021.672929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121317PMC
April 2021

Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy.

Front Cell Dev Biol 2021 29;9:672693. Epub 2021 Apr 29.

State Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, China.

Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate "FLASH-RT" evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼10 Gy/s) at the dose of 6-9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan.
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http://dx.doi.org/10.3389/fcell.2021.672693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116574PMC
April 2021

Marine-Source Quorum Quenching Enzyme YtnP to Improve Hygiene Quality in Dental Units.

Mar Drugs 2021 Apr 16;19(4). Epub 2021 Apr 16.

College of Chemical Engineering, Huaqiao University, Xiamen 361021, China.

Biofilm in dental unit water lines may pose a health risk to patients and dental practitioners. An AdiC-like quorum quenching enzyme, YtnP, was cloned from a deep-sea probiotic , and heterologously expressed in to examine the application on the improvement of hygiene problems caused by biofilm infection of in dental units. bacteria were isolated from dental chair units and used to grow static biofilms in the laboratory. A water filter system was designed to test the antifouling activity of YtnP in Laboratory, to simulate the biofilm contamination on water filter in dental unit water lines. The results demonstrated that the enzyme of YtnP was able to degrade the N-acyl homoserine lactones, significantly inhibited the EPS generation, biofilm formation, and virulence factors production (pyocyanin and rhamnolipid) of , and was efficient on the antifouling against . The findings in this study indicated the possibility of YtnP as novel disinfectant reagent for hygiene treatment in dental units.
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http://dx.doi.org/10.3390/md19040225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073825PMC
April 2021
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