Publications by authors named "Chen Yao"

1,702 Publications

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A Joint Technology Combining the Advantages of Capillary Microsampling with Mass Spectrometry Applied to the Trans-Resveratrol Pharmacokinetic Study in Mice.

J Anal Methods Chem 2022 17;2022:5952436. Epub 2022 Jan 17.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Mice are the most frequently used animals in pharmacokinetic studies; however, collecting series of blood samples from mice is difficult because of their small sizes and tiny vessels. In addition, due to the small sample size, it is problematic to perform high required quantification. Thus, present work aims to find an effective strategy for overcoming these challenges using trans-resveratrol as a tool drug. Based on the idea of a joint technology, the capillary microsampling (CMS) was chosen for blood sample collection from mice after delivery of trans-resveratrol (150 mg/kg) by gavage, and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of trans-resveratrol and its main metabolites. All the mouse blood samples were exactly collected by CMS without obvious deviation. This provided credible samples for subsequent quantitative analysis. The HPLC-MS/MS method was found to be sensitive, accurate, and repeatable, and the pharmacokinetic parameters for all analytes were comparable with those reported in previous studies. However, the present joint technology offers the advantages of less animal damage, easy for sample preparation, and improved reliability. It has overcome some of the major limitations revealed in previous pharmacokinetic studies in mice and therefore provides a more effective option for future studies.
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http://dx.doi.org/10.1155/2022/5952436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786553PMC
January 2022

Patient-derived organoids for personalized gallbladder cancer modelling and drug screening.

Clin Transl Med 2022 Jan;12(1):e678

International Cooperation Laboratory on Signal Transduction, Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Shanghai Key Laboratory of Hepato-biliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies.

Methods: We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole-exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC-101 and CUDC-907, were evaluated in vitro and in vivo.

Results: The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single-cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC-907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids.

Conclusions: Patient-derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.
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http://dx.doi.org/10.1002/ctm2.678DOI Listing
January 2022

Construction of a Novel Ferroptosis-Related Gene Signature of Atherosclerosis.

Front Cell Dev Biol 2021 5;9:800833. Epub 2022 Jan 5.

Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Atheroclerosis refers to a chronic inflammatory disease featured by the accumulation of fibrofatty lesions in the intima of arteries. Cardiovasular events associated with atherosclerosis remain the major causes of mortality worldwide. Recent studies have indicated that ferroptosis, a novel programmed cell death, might participate in the process of atherosclerosis. However, the ferroptosis landscape is still not clear. In this study, 59 genes associated with ferroptosis were ultimately identified in atherosclerosis in the intima. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for functional annotation. Through the construction of protein-protein interaction (PPI) network, five hub genes (, , , , and ) were then validated histologically. The competing endogenous RNA (ceRNA) network of hub genes was ultimately constructed to explore the regulatory mechanism between lncRNAs, miRNAs, and hub genes. The findings provide more insights into the ferroptosis landscape and, potentially, the therapeutic targets of atherosclerosis.
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http://dx.doi.org/10.3389/fcell.2021.800833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766414PMC
January 2022

Electrochemical monitoring the effect of drug intervention on PC12 cell damage model cultured on paper-PLA 3D printed device.

Anal Chim Acta 2022 Feb 29;1194:339409. Epub 2021 Dec 29.

Department of Pharmaceutical Analysis, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350122, China. Electronic address:

Three-dimensional (3D) cell culture system, as an alternative approach for traditional cell culture, attracts great attention because of physiological relevance and great microenvironment similarity to human conditions. Herein, a facile paper-polylactic (PLA) platform that was fabricated by wax printing and 3D printing, coupled with electrochemical sensor, was designed for the construction and intervention of 3D cell damage model. Pheochromocytoma cells (PC12) and bone marrow mesenchymal stem cells (BMSCs) were seeded on the paper-PLA 3D platforms and displayed the features of uniform distribution, good adhesion and perfect proliferation, as well as decreased circularity when compared to those grown on the two-dimensional (2D) interfaces. The electrochemical sensors revealed cell viability by monitoring dopamine released by cell models, ascertaining the applicability of the paper-PLA platform to a long-term 3D cell culture and drug assessment. Additionally, the results revealed that donepezil and BMSCs-secreted active molecules exhibited stronger cytoprotective effect against amyloid-beta oligomers-induced cell damage on the paper-PLA 3D printed platforms, indicating the cell damage model and the cell intervention model were achieved successfully in the simulated in vivo physiological microenvironment. Thus, the proposed paper-PLA platform may serve as a promising candidate for efficient drug screening and toxicity evaluation due to its simple structure, low cost, and convenient integration of 3D cell culture and activity evaluation.
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http://dx.doi.org/10.1016/j.aca.2021.339409DOI Listing
February 2022

Strong synergistic interactions in zwitterionic-anionic surfactant mixtures at the air-water interface and in micelles: The role of steric and electrostatic interactions.

J Colloid Interface Sci 2022 Jan 10;613:297-310. Epub 2022 Jan 10.

ISIS Facility, Rutherford Appleton Laboratory, STFC, Chilton, Didcot, OXOX OX11 0QX, UK; Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK. Electronic address:

Hypothesis: The milder interaction with biosystems makes the zwitterionic surfactants an important class of surfactants, and they are widely used in biological applications and in personal care formulations. An important aspect of those applications is their strong synergistic interaction with anionic surfactants. It is anticipated that the strong interaction will significantly affect the adsorption and self-assembly properties.

Experiments: Surface tension, ST, neutron reflectivity, NR, and small angle neutron scattering, SANS, have been used here to explore the synergistic mixing in micelles and at the air-water interface for the zwitterionic surfactant, dodecyldimethylammonium propanesulfonate, CSB, and the anionic surfactants, alkyl ester sulfonate, AES, in the absence and presence of electrolyte, 0.1 M NaCl.

Findings: At the air-water interface the asymmetry of composition in the strong synergistic interaction and the changes with added electrolyte and anionic surfactant structure reflect the relative contributions of the electrostatic and steric interactions to the excess free energy of mixing. In the mixed micelles the synergy is less pronounced and indicates less severe packing constraints. The micelle structure is predominantly globular to elongated, and shows a pronounced micellar growth with composition which depends strongly upon the nature of the anionic surfactant and the addition of electrolyte.
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http://dx.doi.org/10.1016/j.jcis.2022.01.045DOI Listing
January 2022

A Class of Rigid-Flexible Coupling Crystalline Crosslinked Polymers as Vapomechanical Actuators.

Angew Chem Int Ed Engl 2022 Jan 18. Epub 2022 Jan 18.

Nankai University, Chemistry, Weijin Road 94#, 300071, Tianjin, CHINA.

Fabricating mechanically responsive actuators that can efficiently convert external stimuli into mechanical work is of great significance for real-world applications. Herein, we rationally design a class of rigid-flexible coupling crystalline crosslinked polymers (CCPs) to fabricate vapomechanically responsive actuators. Interfacial condensation reactions of flexible macromers with rigid monomers afford a series of freestanding CCP membranes. Notably, it is the first example that crosslinked polymers show high crystallinity and porosity. Moreover, CCP membranes exhibit good mechanical properties and interesting vapor-triggered actuation performance, which is reversible and repeatable. We find that the unusual polymer structures, high vapor sorption, and anisotropic membranes contribute to the directional deformation performance of CCP actuators. The synthesis approach in this work provides new insights into the design and fabrication of smart materials for advanced applications.
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http://dx.doi.org/10.1002/anie.202117390DOI Listing
January 2022

Engineering Olefin-Linked Covalent Organic Frameworks for Photoenzymatic Reduction of CO2.

Angew Chem Int Ed Engl 2022 Jan 18. Epub 2022 Jan 18.

Nankai University, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Weijin Road 94#, Tianjin, CHINA.

It is of profound significance concerning the global energy and environmental crisis to develop new techniques that can reduce and convert CO 2 . To address this challenge, we build a new type of artificial photoenzymatic system for CO 2 reduction, using a rationally designed mesoporous olefin-linked covalent organic framework (COF) as the porous solid carrier for co-immobilizing formate dehydrogenase (FDH) and Rh-based electron mediator. By adjusting the incorporating content of Rh electronic mediator, which facilitates the regeneration of nicotinamide cofactor (NADH) from NAD + , the apparent quantum yield can reach as high as 9.17±0.44%, surpassing all reported NADH regenerated photocatalysts constructed by crystalline framework materials. Finally, the assembled photocatalyst-enzyme coupled system can selectively convert CO 2 to formic acid with high efficiency and good reusability. This work demonstrates the first example using COFs to immobilize enzymes for artificial photosynthesis systems that utilize solar energy to produce value-added chemicals.
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http://dx.doi.org/10.1002/anie.202200261DOI Listing
January 2022

A γ-glutamyl hydrolase lacking the signal peptide confers susceptibility to folates/antifolates in acute lymphoblastic leukemia cells.

FEBS Lett 2022 Jan 17. Epub 2022 Jan 17.

Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, School of Medicine, Pediatric Translational Medicine Institute, Shanghai Jiao Tong University, China.

A key cofactor of several enzymes implicated in DNA synthesis, repair, and methylation, folate has been shown to be required for normal cell growth and replication and is the basis for cancer chemotherapy using antifolates. γ-Glutamyl hydrolase (GGH) catalyzes the removal of γ-polyglutamate tails of folylpoly-/antifolylpoly-γ-glutamates to facilitate their export out of the cell, thereby maintaining metabolic homeostasis of folates or pharmacological efficacy of antifolates. However, the factors that control or modulate GGH function are not well understood. In this study, we show that intact GGH is not indispensable for the chemosensitivity and growth of acute lymphoblastic leukemia (ALL) cells, whereas GGH lacking N-terminal signal peptide (GGH ) confers the significant drug resistance of ALL cells to the antifolates MTX and RTX. In addition, ALL cells harboring GGH show high susceptibility to the change in folates, and glycosylation is not responsible for these phenotypes elicited by GGH . Mechanistically, the loss of signal peptide enhances intracellular retention of GGH and its lysosomal disposition. Our findings clearly define the in vivo role of GGH in ALL cells and indicate a novel modulation of the GGH function, suggesting new avenues for ALL treatment in future.
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http://dx.doi.org/10.1002/1873-3468.14285DOI Listing
January 2022

Curative effect of kangfuyan capsule combined with antibiotic treatment on pelvic inflammatory disease.

Pak J Pharm Sci 2021 Nov;34(6(Special)):2479-2485

Department of Neurology, the First People's Hospital of Shenyang, Shenyang, Liaoning Province, China.

This study aims to investigate the curative effect of Kangfuyan capsule in the treatment of damp-heat and blood stasis type of pelvic inflammatory disease (PID), and its influence on serum inflammatory factors IL-6, CRP and TNF-α. A total of 83 patients with PID were randomly divided into two groups: Western medicine group (control group, n=41) received oral antibiotics (azithromycin + metronidazole) alone and the traditional Chinese medicine combined with Western medicine group (experimental group, n=42) received Kangfuyan capsule based on Western medicine therapy. Clinical efficacy between these two groups and the influence of drugs in serum inflammatory factors (IL-6, CRP and TNF-α) were compared. The total effective rate was 78.05% in the control group and 97.62% in the experimental group and difference between these two groups was statistically significant (P<0.01). The symptoms and signs in the two groups significantly improved after treatment (P<0.05) and improvement rate was significantly better in the experimental group than in the control group (P<0.05). After treatment, serum inflammatory factor levels in the two groups were significantly lower than levels before treatment (P<0.05) and improvement rate was significantly better in the experimental group than in the control group (P<0.05). Kangfuyan capsule combined with antibiotics can effectively relieve the symptoms and signs of patients, improve the efficiency of treatment, provide high safety, and does not increase adverse reactions. The possible mechanism may be that this therapy suppresses chronic PID by reducing serum inflammatory factor (IL-6, CRP and TNF-α) levels.
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November 2021

Hypermethylation Effects of Yiqihuoxue Decoction in Diabetic Atherosclerosis Using Genome-Wide DNA Methylation Analyses.

J Inflamm Res 2022 8;15:163-176. Epub 2022 Jan 8.

Institute of Geriatric Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People's Republic of China.

Purpose: To investigate if a traditional Chinese medicine formulation, called "Yiqihuoxue" (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation.

Methods: Apolipoprotein E-knockout mice were administered streptozotocin (50 mg/d, i.p.) for 5 days and fed a high-fat diet for 16 weeks. Mice were divided randomly into DA model, rosiglitazone, as well as low-, medium-, and high-dose YQHX groups. Ten healthy C57BL/6J mice were the control group. Serum levels of fasting insulin, blood glucose, homeostasis model-insulin resistance index (HOMA-IR), serum lipids, and inflammatory factors were analyzed after the final treatment. Aorta tissues were collected for staining (hematoxylin and eosin, and Oil red O). Genomic DNA was extracted for methyl-capture sequencing (MC-seq). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze differentially methylated genes. Pyrosequencing was used to verify MC-seq data.

Results: Low-dose and high-dose YQHX could reduce the HOMA-IR ( < 0.05). Low-dose YQHX reduced expression of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), TNF-α, andI L-6 in serum compared with that in the model group ( < 0.05). Medium-dose YQHX decoction inhibited the expression level of TNF-α ( < 0.05). High-dose YQHX decreased the expression level of IL-6 ( < 0.05). Staining also showed the anti-atherosclerosis effects of YQHX ( < 0.05). MC-seq revealed many abnormally hypermethylated and hypomethylated genes in DA mice compared with those in the control group. KEGG database analysis showed that the hypermethylated genes induced by YQHX treatment were related to pathways in cancer, Hippo signaling, and mitogen activated protein kinase. The network analysis suggested that the hypermethylated genes epidermal growth factor receptor() and phosphoinositide-3-kinase regulatory subunit 1() induced by YQHX treatment had important roles in DA. Pyrosequencing revealed that YQHX treatment increased methylation of and significantly ( < 0.05).

Conclusion: YQHX decoction had positive treatment effects against DA, because it could regulate aberrant hypomethylation of DNA.
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http://dx.doi.org/10.2147/JIR.S335374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754469PMC
January 2022

Marital status and survival in laryngeal squamous cell carcinoma patients: a multinomial propensity scores matched study.

Eur Arch Otorhinolaryngol 2022 Jan 16. Epub 2022 Jan 16.

Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No. 1, Minhou County, Fuzhou, 350108, Fujian, People's Republic of China.

Objective: To explore the correlation between the marital status and prognosis of patients with laryngeal squamous cell carcinoma (LSCC).

Study Design: MPSM was adopted to minimize the maximum standardized average difference of the covariates among the four groups with different marital status.

Setting: Multinomial propensity scores matching (MPSM) based on data from the surveillance, epidemiology, and end results (SEER) database.

Methods: The Kaplan-Meier method and log-rank test were used to compare the survival outcomes of these groups with different marital status.

Results: Totally, 16,981 LSCC patients (median [IQR] age 62 [55-69] years; 829 [76.41%] males) from 2004 to 2016 were included in this study. Among them, 9112 (53.66%) were married, 2708 (15.95%) divorced or separated, 1709 (10.06%) widowed, and 3452 (20.33%) single. After MPSM, the weights make the characteristics of four groups with different marital status sufficient balance. The Kaplan-Meier method and log-rank test showed widowed patients may lead to the highest mortality rate while married patients have a higher survival rate than the other three groups. Single and divorced or separated patients had no significant difference in the survival rate. In addition, multivariate analysis by controlling for confounding factors showed that in male, well-differentiated, and early stage patients, compared with married, unmarried was an independent risk factor for CSS (P < 0.05).

Conclusion: Marital status showed a significant association with the survival status of LSCC patients. Importantly, the outcome of married patients was better, while widowed patients tended to have worse prognosis.
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http://dx.doi.org/10.1007/s00405-022-07252-7DOI Listing
January 2022

Objective neuromodulation basis for intrafascicular artificial somatosensation through carbon nanotube yarn electrodes.

J Neurosci Methods 2022 Jan 13;369:109481. Epub 2022 Jan 13.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: Intrafascicular electrical stimulation has been extensively adopted to achieve sensory feedback for limb amputees. Axon-like carbon nanotube yarn (CNTy) electrodes with both promising flexibility and spatial selectivity index (SSI) can be fascinating alternatives to generate artificial somatosensation.

New Method: Here we systematically disclose objective neuromodulation basis for artificial somatosensation through intrafascicular CNTy electrodes. CNTy electrodes with different exposed lengths were utilized for electrically stimulating tibial nerves in twelve rats. Somatosensory evoked potentials (SEPs) were recorded synchronously using an epidural thirty-channel electrode array. Spatiotemporal characteristics of SEPs were analyzed as current pulse amplitude (PA), pulse width (PW) and pulse frequency (PF) varied.

Results: The current thresholds at 1 Hz exhibit the lowest means when compared with those at 4 and 8 Hz for most CNTy electrodes (20/28). For all the electrodes, amplitudes of SEPs and activated areas of perceptive fields increase with PWs and PAs rising, and decrease remarkably with PFs from 1 to 8 Hz. Latencies of P1 and N1 of SEP peaks gradually reduced with PWs and PAs advancing. Considering high SSIs, relatively stable current thresholds, wider variation ranges of sensory magnitudes and optimal stability of perceptive fields, the L-200 µm electrodes are preferable for neuromodulation with PFs of 1 - 8 Hz, PWs of 100 - 800 μs and PAs of 2 - 64 μA.

Comparison With Existing Methods: New-type CNTy electrodes possess both promising flexibility and SSI when compared with other neural interfaces. We systematically explore objective neuromodulation basis for artificial somatosensation through CNTy electrodes for the first time.

Conclusions: Significantly higher SSIs, lower current and charge thresholds exist for CNTy electrodes in comparison with other peripheral-nerve interfaces. This study can, for the first time, lay a solid neuromodulation foundation for CNTy electrodes to achieve fine sensory feedback.
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http://dx.doi.org/10.1016/j.jneumeth.2022.109481DOI Listing
January 2022

Physiological effects induced by aluminium and fluoride stress in tall fescue (Festuca arundinacea Schreb).

Ecotoxicol Environ Saf 2022 Jan 11;231:113192. Epub 2022 Jan 11.

College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China. Electronic address:

Aluminium (Al) and fluoride (F) are phytotoxic elements that can inhibit plant growth and development. Al and F can react with each other to form complexes in the soil which will induce alteration of toxicity of single element. However, the mechanisms of plant response to aluminium fluoride induced toxicity are not very clear. In the present study, tall fescue (Festuca arundinacea Schreb) cultivar 'Houndog 5' was treated by 0, 0.4, 4, 20 mg·L Al(SO) and 0, 0.5, 5 mg·L NaF, respectively. After 25 days of treatment, leaf samples were collected for physiological evaluation. The results showed that several forms of Al-OH and Al-F complexes such as Al(OH), AlOH, Al(OH), Al(OH), Al(OH), Al(OH), AlF, AlF, AlF and AlF were formed in Al and F combined solution. The nutrient uptake including Al, P and K were improved by Al and F. Under Al stress, the MDA (malondialdehyde) content and EL (electrolyte leakage) dramatically increased after high concentration of F treatment, while relative low concentration of F induced decrease of MDA content and EL. On the contrary, chlorophyll content decreased significantly after high concentration of F treatment. The photosynthesis efficiency parameters, including φ (Fv/Fm), δ and PI, decreased remarkably after high concentration of Al and F treatment. However, L-band incresed after high concentration of Al and F treatment. The results of correlation analysis showed that MDA content and EL negatively correlated with other indexes, and Al-F complex significantly correlated with MDA, Pro and EL but negatively correlated with Chl and φ. These results suggested that low concentration of F could alleviate the damage induced by Al stress in tall fescue, but high concentration of Al and F combined solution had negative effects on the growth and development of tall fescue.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113192DOI Listing
January 2022

Thermodynamic and kinetic coupling modeling for thallium(I) sorption at a heterogeneous titanium dioxide interface.

J Hazard Mater 2022 Jan 7;428:128230. Epub 2022 Jan 7.

Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, College of Environment and Ecology, Chongqing University, Chongqing 400044, China.

The transformations of monovalent thallium (Tl) in an aqueous environment may be affected significantly by Tl(I) partitioning at the solid-water interface during sorption. Models used to quantify the kinetics of Tl(I) adsorption on heterogeneous adsorbents and formation of multiple complexes under a wide range of water chemistry conditions can accurately predict the environmental fate of thallium. In this study, Tl(I) sorption on representative titanium dioxide at different solution pH values and loading concentrations was investigated with two unified adsorption models, diffuse layer modeling and kinetics modeling. Three Tl(I) surface complexes, TiOTl, TiOHTl, and TiOTlOH, were used in the diffuse layer model and successfully described batch adsorption and the results of spectroscopic analyses. The contribution of TiOHTl to the adsorption capacity was much higher than those of TiOTl and TiOTlOH under neutral and weakly alkaline conditions, while the species TiOTlOH predominated among Tl(I) complexes in strongly alkaline environments. The adsorption and desorption rate coefficients derived from thermodynamics and kinetics coupling modeling suggested the influence of different complex characteristics on adsorption and desorption of Tl(I). Our results provide a comprehensive model for predicting the dynamic binding behavior of Tl at heterogeneous solid-water interfaces.
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http://dx.doi.org/10.1016/j.jhazmat.2022.128230DOI Listing
January 2022

BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection.

Sci Immunol 2022 Jan 14;7(67):eabc9934. Epub 2022 Jan 14.

Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53213, USA.

[Figure: see text].
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http://dx.doi.org/10.1126/sciimmunol.abc9934DOI Listing
January 2022

Pharmacotranscriptomic profiling of resistant triple-negative breast cancer cells treated with lapatinib and berberine shows upregulation of PI3K/Akt signaling under cytotoxic stress.

Gene 2022 Jan 10;816:146171. Epub 2022 Jan 10.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou 646000, Sichuan, PR China. Electronic address:

Triple-negative breast cancer (TNBC) is the most incurable type of breast cancer, accounting for 15-20% of breast cancer cases. Lapatinib is a dual tyrosine kinase inhibitor targeting EGFR and Her2, and berberine (BBR) is a plant-based alkaloid suggested to inhibit several cancer signaling pathways. We previously reported that lapatinib activates the Akt oncoprotein in MDA-MB231 TNBC cells. The present study determined the mechanism(s) of Akt activation in response to lapatinib, BBR, and capivasertib (Akt inhibitor) as well as the role of Akt signaling in chemoresistance in TNBC cells. Genetic profiles of 10 TNBC cell lines and patients were analyzed using datasets obtained from Gene Expression Omnibus and The Cancer Genome Atlas Database. Then, the effects of lapatinib, BBR, and capivasertib on treated MDA-MB231 and MCF-7 cell lines were studied using cytotoxicity, immunoblot, and RNA-sequencing analyses. For further confirmation, we also performed real-time PCR for genes associated with PI3K signaling. MDA-MB231 and MCF-7 cell lines were both strongly resistant to capivasertib largely due to significant Akt activation in both breast cancer cell lines, while lapatinib and BBR only enhanced Akt signaling in MDA-MB231 cells. Next-generation sequencing, functional enrichment analysis, and immunoblot revealed downregulation of CDK6 and DNMT1 in response to lapatinib and BBR lead to a decrease in cell proliferation. Expression of placental, fibroblast growth factor, and angiogenic biomarker genes, which are significantly associated with Akt activation and/or dormancy in breast cancer cells, was significantly upregulated in TNBC cells treated with lapatinib and BBR. Lapatinib and BBR activate Akt through upregulation of alternative signaling, which lead to chemoresistance in TNBC cell. In addition, lapatinib overexpresses genes related to PI3K signaling in resistant TNBC cell model.
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http://dx.doi.org/10.1016/j.gene.2021.146171DOI Listing
January 2022

Fucoidans from ameliorate renal interstitial fibrosis inhibition of the PI3K/Akt/NF-κB signaling pathway.

Food Funct 2022 Jan 12. Epub 2022 Jan 12.

Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.

The effects of polysaccharides (CFPs) on renal interstitial fibrosis by regulating the phosphatidylinositol-3-hydroxykinase/protein kinase-B/nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated and in this research. The common unilateral urethral obstruction (UUO) model was used to examine the renoprotective effect and its mechanism . Compared to the UUO group, CFP administration could ameliorate renal function, inhibit inflammation and fibrosis, and reduce the deposition of the extracellular matrix and epithelial-mesenchymal transition. Mechanistic results indicated that CFPs could inhibit the expression of the total protein of PI3K and the conversion of the AKT and NF-κB p65 phosphorylated proteins, thereby inhibiting the transduction of the PI3K/AKT/NF-κB pathway. In addition, CFP treatment could improve inflammation and fibrosis in HK-2 cells induced by TGF-β1, and its mechanism was also verified to inhibit the PI3K/Akt/NF-κB signaling pathway. Overall, these results showed that CFP could alleviate renal interstitial fibrosis related to the PI3K/AKT/NF-κB signaling pathway.
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http://dx.doi.org/10.1039/d1fo03067aDOI Listing
January 2022

A Theoretical Study on the Borane-Catalyzed Reductive Amination of Aniline and Benzaldehyde with Dihydrogen: The Origins of Chemoselectivity.

J Org Chem 2022 Jan 12;87(2):1194-1207. Epub 2022 Jan 12.

School of Life Science and Chemistry, Jiangsu Second Normal University, Nanjing, Jiangsu 210013, China.

Density functional theory calculations are used in this study to investigate the product selectivity and mechanism of borane-catalyzed reductive aldehyde amination by a H reducing agent. Knowing that different boranes yield different products, two typical boranes, (B(2,6-ClCH)(-HCF) and B(CF)), are studied. Of the seven possible pathways of B(2,6-ClCH)(-HCF)-catalyzed aldehyde amination analyzed herein, four are favorable. Three of the four favorable pathways involve imine intermediates, and the fourth is a Lewis acid-base synergistic pathway that involves amine-alcohol condensation. As for the B(CF) catalyst, it forms a highly stable Lewis adduct with aniline, which impedes the hydrogenation of imine. Therefore, the product of B(CF)-catalyzed reductive amination of benzaldehyde and aniline is an imine. The linear relationship between the charge on the boron atom in the Lewis acid and the relative energies of the Lewis adduct and H splitting transition state indicates that this parameter determines product selectivity. Indeed, when the natural charge on boron is larger than 1, an amine is produced, whereas when the charge is less than 1, an imine is produced. Hence, the selectivity of products can be controlled by adjusting the natural charge of the boron atom in the Lewis acid catalyst.
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http://dx.doi.org/10.1021/acs.joc.1c02491DOI Listing
January 2022

Single cell immune profiling reveals a developmentally distinct CD4+ GM-CSF+ T cell lineage that induces GI tract GVHD.

Blood Adv 2022 Jan 11. Epub 2022 Jan 11.

Medical College of Wisconsin, Milwaukee, Wisconsin, United States.

Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft versus host disease (GVHD). CD4+ T cells that produce GM-CSF have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if there exists a unique CD4+ GM-CSF+ subset that differs from other defined T helper (TH) subtypes. Using single cell RNA sequencing analysis, we identified two CD4+ GM-CSF+ T cell populations that arose during GVHD and were distinguishable by the presence or absence of IFN-γ co-expression. CD4+ GM-CSF+ IFN-γ- T cells which emerged preferentially in the colon had a distinct transcriptional profile, employed unique gene regulatory networks, and possessed a non-overlapping TCR repertoire when compared to CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T cell populations in the colon. Functionally, this CD4+ GM-CSF+ T cell population contributed to pathological damage in the GI tract which was critically dependent upon signaling through the IL-7 receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic TH GM-CSF+ subset that mediates immunopathology.
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http://dx.doi.org/10.1182/bloodadvances.2021006084DOI Listing
January 2022

A prognostic nomogram for intrahepatic progression-free survival in patients with colorectal liver metastases after ultrasound-guided percutaneous microwave ablation.

Int J Hyperthermia 2022 ;39(1):144-154

Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Purpose: The present study identified predictors of intrahepatic progression-free survival (ihPFS) after ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs) and developed a nomogram to predict ihPFS.

Methods: From January 2013 to December 2018, a total of 314 patients (224 men and 90 women; mean age, 57.1 ± 11.8 years; range, 23-86 years) with 645 CRLMs (mean diameter, 16.6 ± 6.5 mm; range, 6.0-45.0 mm) treated with US-guided percutaneous MWA were included and analyzed. The average number of CRLMs per patient treated was 2 (range, 1-8). A nomogram to predict ihPFS was developed based on a multivariable Cox model. Validation of the nomogram was performed using the concordance index (C-index), calibration curves, and decision curve analyses.

Results: The 1-, 2-, and 3-year cumulative ihPFS rates were 59.0%, 38.9%, and 30.8%, respectively. Maximal CRLM size, number of CRLMs, ablative margin, primary tumor lymph node status, and chemotherapy were five independent prognostic factors for ihPFS. The C-index of the nomogram was 0.702 (CI: 0.681-0.723). A risk classification system that perfectly classified the patients into three risk groups was constructed. The median ihPFS of patients in the low-, intermediate-, and high-risk groups was 36.3 months (95% CI: 21.4-51.1), 13.4 months (95% CI: 12.1-14.6), and 3.8 months (95% CI: 2.3-5.3), respectively.

Conclusion: The nomogram and risk classification system will facilitate the personalized assessment of ihPFS for patients receiving US-guided percutaneous MWA for CRLMs.
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http://dx.doi.org/10.1080/02656736.2021.2023226DOI Listing
January 2022

Root Canal Disinfection Using Highly Effective Aggregation-Induced Emission Photosensitizer.

ACS Appl Bio Mater 2021 May 7;4(5):3796-3804. Epub 2020 Dec 7.

Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, The Affiliated Stomatological Hospital of Nankai University, Tianjin 300041, China.

Root canal (RC) therapy is the primary treatment of dental-pulp and periapical diseases. The mechanical method and chemical irrigation have limitations in RC therapy. Much attention has focused on exploring more controllable and efficacious antimicrobial methods. Although the introduction of photodynamic therapy (PDT) has provided the ideas for RC debridement, the problems of low photosensitive efficiency and nonsignificant germicidal potency of traditional photosensitizers (e.g., methylene blue) have not been solved. Since the concept of "aggregation-induced emission" (AIE) was proposed, optimization of photosensitizers has been boosted considerably. Herein, an AIE photosensitizer, DPA-SCP, with a strong ability to generate singlet oxygen, is proposed for use as an antibacterial application in infected RCs. The antimicrobial activity of DPA-SCP against suspensions was tested. To explore the antibacterial ability of this photosensitizer against bacterial-biofilm colonization on the inner walls of RCs, we established a model of bacterial biofilm infection. PDT mediated by DPA-SCP had a significant germicidal effect on suspensions and 21-day biofilms in human RCs. PDT mediated by DPA-SCP could achieve efficiency equivalent to that observed using 1% NaOCl, and lead to no significant change in the dentin surface, chemical corrosion, or cytotoxicity.
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http://dx.doi.org/10.1021/acsabm.0c01274DOI Listing
May 2021

Corrigendum: Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer's Disease.

Front Aging Neurosci 2021 20;13:815251. Epub 2021 Dec 20.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

[This corrects the article DOI: 10.3389/fnagi.2021.750921.].
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http://dx.doi.org/10.3389/fnagi.2021.815251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721959PMC
December 2021

Mitochondrial STAT3 exacerbates LPS-induced sepsis by driving CPT1a-mediated fatty acid oxidation.

Theranostics 2022 1;12(2):976-998. Epub 2022 Jan 1.

Department of Hematology, Fukushima Medical University, Fukushima, Japan.

We found that a subset of signal transducer and activator of transcription 3 (STAT3) translocated into mitochondria in phagocytes, including macrophages isolated from individuals with sepsis. However, the role of mitochondrial STAT3 in macrophages remains unclear. To investigate the function of mitochondrial STAT3 , we generated inducible mitochondrial STAT3 knock-in mice. A cytokine array analysis, a CBA analysis, flow cytometry, immunofluorescence staining and quantification and metabolic analyses were subsequently performed in an LPS-induced sepsis model. Single-cell RNA sequencing, a microarray analysis, metabolic assays, mass spectrometry and ChIP assays were utilized to gain insight into the mechanisms of mitochondrial STAT3 in metabolic reprogramming in LPS-induced sepsis. We found that mitochondrial STAT3 induced NF-κB nuclear localization and exacerbated LPS-induced sepsis in parallel with a metabolic switch from mainly using glucose to an increased reliance on fatty acid oxidation (FAO). Moreover, mitochondrial STAT3 abrogated carnitine palmitoyl transferase 1a (CPT1a) ubiquitination and degradation in LPS-treated macrophages. Meanwhile, an interaction between CPT1a and ubiquitin-specific peptidase 50 (USP50) was observed. In contrast, knocking down USP50 decreased CPT1a expression and FAO mediated by mitochondrial STAT3. The ChIP assays revealed that NF-κB bound the USP50 promoter. Curcumin alleviated LPS-mediated sepsis by suppressing the activities of mitochondrial STAT3 and NF-κB. Our findings reveal that mitochondrial STAT3 could trigger FAO by inducing CPT1a stabilization mediated by USP50 in macrophages, at least partially.
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http://dx.doi.org/10.7150/thno.63751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692896PMC
January 2022

A genomic approach identifies sRAGE as a putatively causal protein for asthma.

J Allergy Clin Immunol 2021 Dec 30. Epub 2021 Dec 30.

Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, 31 Center Drive, Ste 10-7C114, Bethesda, MD 20891, USA; Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA. Electronic address:

Background: Asthma is a complex respiratory condition caused by environmental and genetic factors. Although lower concentrations of the anti-inflammatory protein sRAGE have been associated with asthma in humans and mouse models, it is uncertain whether sRAGE plays a causal role in asthma.

Objective: We designed a two-stage study of sRAGE in relation to asthma with i) association analysis in FHS participants and ii) causal inference testing using MR.

Methods: We measured plasma levels of sRAGE and performed cross-sectional analysis to examine the association between plasma sRAGE concentration and asthma status in 6,546 FHS participants. We then used sRAGE pQTLs derived from a GWAS of plasma sRAGE levels in ∼7,000 FHS participants with UK Biobank asthma GWAS in MR to consider sRAGE as a putatively causal protein for asthma. We also performed replication MR using an externally-derived sRAGE pQTL from the INTERVAL study. Last, we conducted colocalization using cis-pQTL variants at the AGER locus with variants from the UK Biobank asthma GWAS.

Results: Association analysis revealed that each 1 SD increment in sRAGE concentration was associated with a 14% lower odds of asthma in FHS participants (95% CI 0.76-0.96). MR identified sRAGE as putatively causal for and protective against asthma based on self-reported (OR [per 1 SE increment in inverse rank-normalized sRAGE]=0.97, 95% CI 0.95-0.99; p=0.005) and doctor-diagnosed asthma (OR=0.97, 95% CI 0.95-0.99; p=0.011).

Conclusion: Through this genomic approach, we identified sRAGE as a putatively causal, biologically important, and protective protein in relation to asthma. Functional studies in cell/animal models are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.jaci.2021.11.027DOI Listing
December 2021

Review of the environmental occurrence/analytical techniques, degradation and toxicity of TBBPA and its derivatives.

Environ Res 2021 Dec 29;206:112594. Epub 2021 Dec 29.

Institute of Environmental Health and Ecological Security, School of Environment and Safety Engineering, Jiangsu University, 212013, PR China. Electronic address:

BFRs (brominated flame retardants) are a class of compounds that are added to or applied to polymeric materials to avoid or reduce the spread of fire. Tetrabromobisphenol A (TBBPA) is one of the known BFR used many in industries today. Due to its wide application as an additive flame retardant in commodities, TBBPA has become a common indoor contaminant. Despite the detection of TBBPA and its derivatives in various environmental and biological samples, information on its occurrence in biota is scarce. TBBPA has been shown to possess immunotoxic, cytotoxic, thyroid hormone agonist, estrogenic activity, reproductive, hepatotoxicity, teratogenicity and neurotoxicity in previous studies. In this review, we evaluated the environmental occurrence of TBBPA (and its derivatives) in different environmental compartments using various analytical techniques, the transformation of TBBPA into various derivatives and the toxicity of TBBPA and its derivatives as well as outlining the possible mechanisms of actions. This review will go a long way in closing up the knowledge gap on the silent and over ignored deadly effects of TBBPA and its derivatives and their attendant consequences.
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http://dx.doi.org/10.1016/j.envres.2021.112594DOI Listing
December 2021

Label-free and sensitive microRNA detection method based on the locked nucleic acid assisted fishing amplification strategy.

Talanta 2022 Apr 22;240:123169. Epub 2021 Dec 22.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan, 410082, PR China.

Herein, a label free and sensitive miRNA detection method with enhanced practical applicability was developed based on the locked nucleic acid (LNA) assisted repeated fishing amplification strategy. The working mechanism of the proposed method is as follows: 1) a DNA probe (i.e, L-DNA) with LNA bases is immobilized onto the surface of a gold foil. The L-DNA hybridizes with the 3' terminus of the first strands of complementary deoxyribonucleic acid (cDNA) of the target miRNA in the test samples; 2) The protruding 5' terminus of the cDNA serves as a 'fishhook' to repeatedly fish the products of a hybridization chain reaction (HCR) out from a 'reaction tube'; 3) The HCR products can be unloaded from the gold foil into a 'product tube' through temperature-controlled dehybridization; 4) The concentration of the target miRNA is determined based on the fluorescence intensity generated by the addition of SYBR-Green I (SG) into the 'product tube'. The proposed platform was applied to the detection of miRNA-122 in cell lysate samples and obtained quantitative results with accuracy comparable to the quantitative reverse transcription PCR method (qRT-PCR). It is worth pointing out that the proposed platform achieved a limit of detection value of 2.9 fM for miRNA-122 by a simple but effective LNA-assisted repeated fishing amplification strategy instead of complicated enzyme-based amplification techniques. It is reasonable to expect that the proposed method provides a competitive alternative for designing practically applicable, cost-effective and label-free miRNA detection methods.
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http://dx.doi.org/10.1016/j.talanta.2021.123169DOI Listing
April 2022

Geographical origin traceability of traditional Chinese medicine Atractylodes macrocephala Koidz. by using multi-way fluorescence fingerprint and chemometric methods.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Mar 10;269:120737. Epub 2021 Dec 10.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.

Atractylodes macrocephala Koidz. (AM) is an important plant of traditional Chinese medicine (TCM), and its status can be comparable with ginseng in China. The efficacy and quality of AM are closely related to the place of origin. Hence, we proposed a simple and fast strategy to classify AM from different geographical origins by using multi-way fluorescence fingerprint combined with chemometric methods. AM samples with different dilution levels have different fluorescence characteristics, resulting from different content of fluorescence components and chemical microenvironment. Therefore, AM samples were diluted 5-fold, 10-fold, and 20-fold with 40% ethanol aqueous solution to obtain excitation-emission matrix data, and multi-way (three-way and four-way) data arrays were constructed. And then, the fluorescence fingerprints of AM samples were characterized by three-way and four-way parallel factor analysis (PARAFAC). In addition, four pattern recognition methods were used to classify AM from different provinces. The results show that the four-way data array can provide more abundant information than three-way data arrays, so it is more conducive to sample classification. According to the results obtained from the analysis of four-way data array, the correct classification rate (CCR) of the cross-validation and prediction set obtained by partial least squares-discrimination analysis (PLS-DA) were 90.5% and 100%, respectively. To sum up, the proposed method can be regarded as a powerful, feasible, convenient, reliable, and universal classification tool for the classification of AM samples from different provinces and can be used as a promising method to realize the geographical origin traceability of other TCMs.
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http://dx.doi.org/10.1016/j.saa.2021.120737DOI Listing
March 2022

Ellis Fruit Extracts Attenuated Colitis in 2,4,6-Trinitrobenzenesulfonic Acid-Induced Rats.

Evid Based Complement Alternat Med 2021 15;2021:9920379. Epub 2021 Dec 15.

School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330006, China.

Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1, TNF-, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation.
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http://dx.doi.org/10.1155/2021/9920379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694976PMC
December 2021

Nano-enabled agrochemicals/materials: Potential human health impact, risk assessment, management strategies and future prospects.

Environ Pollut 2022 Feb 21;295:118722. Epub 2021 Dec 21.

Institute of Environmental Health and Ecological Security, School of Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013 PR China.

Nanotechnology is a rapidly developing technology that will have a significant impact on product development in the next few years. The technology is already being employed in cutting-edge cosmetic and healthcare products. Nanotechnology and nanoparticles have a strong potential for product and process innovation in the food industrial sector. This is already being demonstrated by food product availability made using nanotechnology. Nanotechnologies will have an impact on food security, packaging materials, delivery systems, bioavailability, and new disease detection materials in the food production chain, contributing to the UN Millennium Development Goals targets. Food products using nanoparticles are already gaining traction into the market, with an emphasis on online sales. This means that pre- and post-marketing regulatory frameworks and risk assessments must meet certain standards. There are potential advantages of nanotechnologies for agriculture, consumers and the food industry at large as they are with other new and growing technologies. However, little is understood about the safety implications of applying nanotechnologies to agriculture and incorporating nanoparticles into food. As a result, policymakers and scientists must move quickly, as regulatory systems appear to require change, and scientists should contribute to these adaptations. Their combined efforts should make it easier to reduce health and environmental impacts while also promoting the economic growth of nanotechnologies in the food supply chain. This review highlighted the benefits of a number of nano enabled agrochemicals/materials, the potential health impacts as well as the risk assessment and risk management for nanoparticles in the agriculture and food production chain.
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http://dx.doi.org/10.1016/j.envpol.2021.118722DOI Listing
February 2022

Intraoperative HIFU Ablation of the Pancreas Using a Toroidal Transducer in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer.

Cancers (Basel) 2021 Dec 20;13(24). Epub 2021 Dec 20.

LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, F-69003 Lyon, France.

Apart from palliative chemotherapy, no other therapy has been proven effective for the treatment of locally advanced pancreatic tumors. In this study, an intraoperative high-intensity focused ultrasound (HIFU) device was tested in vivo to demonstrate the feasibility of treating the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels prior to clinical translation of this technique. Twenty pigs were included and treated using a HIFU device equipped with a toroidal transducer and an integrated ultrasound imaging probe. Treatments were performed with energy escalation (from 30 kJ to 52 kJ). All treatments resulted in visible (macroscopically and in ultrasound images) homogeneous thermal damage, which was confirmed by histology. The dimensions of thermal lesions measured in ultrasound images and those measured macroscopically were correlated (r = 0.82, < 0.05). No arterial spasms or occlusion were observed at the lowest energy setting. Temporary spasm of the peripancreatic artery was observed when using an energy setting greater than 30 kJ. The possibility of treating the pancreas and tissues around mesenteric vessels without vascular thrombosis holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option for locally advanced pancreatic cancer.
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http://dx.doi.org/10.3390/cancers13246381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699564PMC
December 2021
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