Publications by authors named "Ming Li"

6,485 Publications

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Intrinsic ferroelectricity in Y-doped HfO thin films.

Nat Mater 2022 Jun 27. Epub 2022 Jun 27.

Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln, NE, USA.

Ferroelectric HfO-based materials hold great potential for the widespread integration of ferroelectricity into modern electronics due to their compatibility with existing Si technology. Earlier work indicated that a nanometre grain size was crucial for the stabilization of the ferroelectric phase. This constraint, associated with a high density of structural defects, obscures an insight into the intrinsic ferroelectricity of HfO-based materials. Here we demonstrate that stable and enhanced polarization can be achieved in epitaxial HfO films with a high degree of structural order (crystallinity). An out-of-plane polarization value of 50 μC cm has been observed at room temperature in Y-doped HfO(111) epitaxial thin films, with an estimated full value of intrinsic polarization of 64 μC cm, which is in close agreement with density functional theory calculations. The crystal structure of films reveals the Pca2 orthorhombic phase with small rhombohedral distortion, underlining the role of the structural constraint in stabilizing the ferroelectric phase. Our results suggest that it could be possible to exploit the intrinsic ferroelectricity of HfO-based materials, optimizing their performance in device applications.
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http://dx.doi.org/10.1038/s41563-022-01282-6DOI Listing
June 2022

A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear Cell Renal Cell Carcinoma.

Cancer Discov 2022 Jun 27. Epub 2022 Jun 27.

Memorial Sloan Kettering Cancer Center, New York, NY, United States.

It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear cell renal cell carcinoma (ccRCC). Here we perform whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identifies myeloid-derived interleukin-6 (IL-6) as a key mediator. Furthermore, a novel myeloid gene signature strongly correlates with disease recurrence and overall survival on uni- and multivariate analysis and is linked to TP53 inactivation across multiple datasets. Strikingly, effector T cell gene signatures, infiltration patterns, and exhaustion markers were not associated with disease recurrence. Targeting immunosuppressive myeloid inflammation with an adenosine A2A receptor antagonist in a novel, immunocompetent, Tp53-inactivated mouse model significantly reduces metastatic development. Our findings suggest myeloid inflammation promotes disease recurrence in ccRCC, is targetable, and provide a potential biomarker-based framework for the design of future immuno-oncology trials in ccRCC.
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http://dx.doi.org/10.1158/2159-8290.CD-21-0925DOI Listing
June 2022

Assessment of the electrical penetration of cell membranes using four-frequency impedance cytometry.

Microsyst Nanoeng 2022 24;8:68. Epub 2022 Jun 24.

Division of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara, 630-0192 Japan.

The electrical penetration of the cell membrane is vital for determining the cell interior via impedance cytometry. Herein, we propose a method for determining the conductivity of the cell membrane through the tilting levels of impedance pulses. When electrical penetration occurs, a high-frequency current freely passes through the cell membrane; thus, the intracellular distribution can directly act on the high-frequency impedance pulses. Numerical simulation shows that an uneven intracellular component distribution can affect the tilting levels of impedance pulses, and the tilting levels start increasing when the cell membrane is electrically penetrated. Experimental evidence shows that higher detection frequencies (>7 MHz) lead to a wider distribution of the tilting levels of impedance pulses when measuring cell populations with four-frequency impedance cytometry. This finding allows us to determine that a detection frequency of 7 MHz is able to pass through the membrane of () cells. Additionally, we provide a possible application of four-frequency impedance cytometry in the biomass monitoring of single cells. High-frequency impedance (≥7 MHz) can be applied to monitor these biomass changes, and low-frequency impedance (<7 MHz) can be applied to track the corresponding biovolume changes. Overall, this work demonstrates an easy determination method for the electrical penetration of the cell membrane, and the proposed platform is applicable for the multiparameter assessment of the cell state during cultivation.
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http://dx.doi.org/10.1038/s41378-022-00405-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226050PMC
June 2022

Simultaneous Detection of Pathogens and Tumors in Patients With Suspected Infections by Next-Generation Sequencing.

Front Cell Infect Microbiol 2022 9;12:892087. Epub 2022 Jun 9.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

Background: Differential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. This study aimed to explore the clinical value of metagenomic next-generation sequencing (mNGS) for tumor detection in patients with suspected infections.

Methods: A multicenter, prospective case study involving patients diagnosed with suspected infections was conducted in four hospitals in Shanghai, China between July 2019 and January 2020. Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new procedure named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in all of the collected samples from patients.

Results: Of 140 patients screened by Onco-mNGS testing, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The positive percent agreement and negative percent agreement of mNGS testing compared to clinical diagnosis was 53.0% (61/115) and 60% (15/25), 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both 0.01). (14.8%, 9/61) was the most common pathogen detected by mNGS, followed by (11.5%, 7/61) and viruses (11.5%, 7/61). The chromosomal abnormalities of the 17 cases included genome-wide variations and local variations of a certain chromosome. Five of 17 patients had a final confirmed with malignant tumors, including three lung adenocarcinomas and two hematological tumors; one patient was highly suspected to have lymphoma; and 11 patients had a prior history of malignant tumor.

Conclusion: This preliminary study demonstrates the feasibility and clinical value of using Onco-mNGS to simultaneously search for potential pathogens and malignant tumors in patients with suspected infections.
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http://dx.doi.org/10.3389/fcimb.2022.892087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218804PMC
June 2022

What are the disease burden and its sensitivity analysis of workers exposing to Staphylococcus aureus bioaerosol during warm and cold periods in a wastewater treatment plant?

Environ Sci Pollut Res Int 2022 Jun 27. Epub 2022 Jun 27.

School of Environmental Studies, China University of Geosciences, 388 Lumo Road, Wuhan, 430074, People's Republic of China.

Biological treatment in wastewater treatment plants releases high amounts of pathogenic bioaerosols. Quantitative microbial risk assessment is a framework commonly used for quantitative risk estimation for occupational exposure scenarios. However, the quantitative contributions of health-risk-estimate inputted parameters remain ambiguous. Therefore, this research aimed to study the disease burden of workers exposed to Staphylococcus aureus bioaerosol during warm and cold periods and strictly quantify the contributions of the inputted parameters by sensitivity analysis on the basis of Monte Carlo simulation. Results showed that the disease health risk burden of workers in the warm period was 1.15-6.11 times higher than that of workers in the cold period. The disease health risk burden of workers without personal protective equipment was 23.83-36.55 times higher than that of workers with personal protective equipment. Sensitivity analysis showed that exposure concentration and aerosol ingestion rate were the first and second predominant factors, respectively; the sensitivity partitioning coefficient of the former was 1.17-1.35 times the value of the latter. In addition, no remarkable differences were revealed in the sensitivity percentage ratio between warm and cold periods. The findings could contribute to the mitigation measures for the management of public health risks.
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http://dx.doi.org/10.1007/s11356-022-21447-9DOI Listing
June 2022

CCN-CL: A content-noise complementary network with contrastive learning for low-dose computed tomography denoising.

Comput Biol Med 2022 Jun 20;147:105759. Epub 2022 Jun 20.

School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China; Medical Imaging Department, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China. Electronic address:

In recent years, low-dose computed tomography (LDCT) has played an increasingly important role in the diagnosis CT to reduce the potential adverse effects of x-ray radiation on patients while maintaining the same diagnostic image quality. Current deep learning-based denoising methods applied to LDCT imaging only use normal dose CT (NDCT) images as positive examples to guide the denoising process. Recent studies on contrastive learning have proved that the original images as negative examples can also be helpful for network learning. Therefore, this paper proposes a novel content-noise complementary network with contrastive learning for an LDCT denoising task. First, to better train our proposed network, a contrastive learning loss, taking the NDCT image as a positive example and the original LDCT image as a negative example to guide the network learning is added. Furthermore, we also design a network structure that combines content-noise complementary learning strategy, attention mechanism, and deformable convolution for better network performance. In an evaluation study, we compare the performance of our designed network with some of the state-of-the-art methods in the 2016 NIH-AAPM-Mayo Clinic Low Dose CT Grand Challenge dataset. The quantitative and qualitative evaluation results demonstrate the feasibility and effectiveness of applying our proposed CCN-CL network model as a new deep learning-based LDCT denoising method.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105759DOI Listing
June 2022

Differences in Brain Activity Between Dopa-Responsive and -Unresponsive Pain in Parkinson's Disease.

Pain Ther 2022 Jun 25. Epub 2022 Jun 25.

Department of Neurology, Henan Provincial People's Hospital, Weiwu Road, Building 7, Zhengzhou, 450003, Henan Province, People's Republic of China.

Introduction: Pain in Parkinson's disease is poorly understood, and most patients with pain do not respond to dopaminergic drugs. We aimed to explore the mechanisms of dopa-responsive and -unresponsive pain by comparing such patients against patients without pain in terms of neural activity and functional connectivity in the brain.

Methods: We prospectively examined 31 Parkinson's patients with dopa-responsive pain, 51 with dopa-unresponsive pain and 93 without pain using resting-state functional magnetic resonance imaging. Neural activity was assessed in terms of the amplitude of low-frequency fluctuation, while functional connectivity was assessed based on analysis of regions of interest.

Results: Patients with dopa-unresponsive pain showed significantly higher amplitude of low-frequency fluctuation in the right parahippocampal/lingual region than patients with no pain. However, there was no amplitude difference between the dopa-responsive pain group and the no pain group. Patients with dopa-unresponsive pain also differed significantly from patients with no pain in their functional connections between the superior temporal gyrus and other areas of cerebral cortex, between amygdala and thalamus and between the amygdala and putamen. Patients with dopa-responsive pain differed significantly from patients with no pain in their functional connections between temporal fusiform cortex and cerebellum, between precentral gyrus and temporal fusiform cortex and between precentral gyrus and cerebellum.

Conclusions: Regional neural activity and functional connectivity in the brain differ substantially among Parkinson's patients with dopa-unresponsive pain, dopa-responsive pain or no pain. Our results suggest that dopa-responsive and -unresponsive pain may arise through different mechanisms, which may help guide the development of targeted therapies.
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http://dx.doi.org/10.1007/s40122-022-00404-xDOI Listing
June 2022

Effect of ozone pretreatment on biogranulation with partial nitritation - Anammox two stages for nitrogen removal from mature landfill leachate.

J Environ Manage 2022 Sep 3;317:115470. Epub 2022 Jun 3.

Engelbart (Beijing) Eco-Tech Co., Ltd., Beijing, 101300, China.

Due to the extremely low C/N ratio, high concentration of ammonia nitrogen and refractory organic matter of mature landfill leachate (MLL), appropriate processes should be selected to effectively remove nitrogen and reduce disposal costs. Partial nitritation (PN) and anaerobic ammonia oxidation (AMX) have been used as the main nitrogen removal processes for MLL, and the sludge granulation in PN and AMX processes could contribute to high biological activity, good sedimentation performance, and stable resistance to toxicity. In this study, the O-PN-AMX biogranules process was selected to effectively remove nitrogen from MLL without carbon addition and pH adjustment. Without uneconomical NH-N oxidation and wasting the alkalinity of MLL, ozone pretreatment achieved color removal, decreased humic- and fulvic-like acid substances, and alleviated the MLL toxicity on ammonia oxidizers. In addition, the ozonation of MLL could shorten the start-up time and improve the treatment efficiency and biogranules stability of PN and AMX processes. Efficient and stable nitritation was achieved in PN reactor without strict dissolved oxygen (DO) control, which was attributed to the unique structure of granular sludge, ozone pretreatment, and alternating inhibition of free ammonia and free nitric acid on nitrite oxidizers. Through the application of ozone pretreatment and granular sludge, the nitrogen removal rate (NRR) and nitrogen removal efficiency (NRE) of the O-PN-AMX biogranules process reached 0.39 kg/m/day and 85%, respectively, for the undiluted MLL treatment. This study might provide a novel and effective operation strategy of combined process for the efficient, economical, and stable nitrogen removal from MLL.
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http://dx.doi.org/10.1016/j.jenvman.2022.115470DOI Listing
September 2022

Surface urban heat island and its relationship with land cover change in five urban agglomerations in China based on GEE.

Environ Sci Pollut Res Int 2022 Jun 24. Epub 2022 Jun 24.

College of Geography and Environmental Science, Northwest Normal University, Lanzhou, 730070, China.

The development of urbanization has changed the original land cover and exacerbated the urban heat island effect, seriously affecting the sustainable development of the ecological environment. Research on urban heat island characteristics and land cover changes in five major urban agglomerations in China to provide a reference for preventing thermal environmental risks and urban agglomeration construction planning. This paper estimates the surface urban heat island intensity (SUHII) of the five major urban agglomerations in China from 2003 to 2019 based on Google Earth Engine (GEE) through the urban-rural dichotomy, analyzes their trends through the Sen + M-K trend analysis method, and combines the detrending rate matrix to analyze the impact of land cover type shift on urban heat island change. Research shows that (1) the land cover types of the five major urban agglomerations in China have changed considerably from 2003 to 2019, and all five major urban agglomerations in China experienced varying degrees of urban expansion. (2) The annual average value of SUHII decreases in Beijing-Tianjin-Hebei, Yangtze River Delta, and middle reaches of the urban agglomerations, while the annual average value of SUHII increases in Chengdu-Chongqing and Pearl River Delta urban agglomerations. (3) The spatial composition of land cover types in the five major urban agglomerations in China is highly spatially correlated with urban heat islands, with urban land and bare land urban heat islands being the most pronounced. (4) The land cover type shift has the most significant heat island impact on Beijing-Tianjin-Hebei, Yangtze River Delta, and Chengdu-Chongqing urban agglomerations. (5) The land cover change (LCC) with an increasing trend in SUHII is mainly bare land converted to arable land, and water bodies, grassland, forest land, and arable land converted to urban land.
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http://dx.doi.org/10.1007/s11356-022-21452-yDOI Listing
June 2022

Modeling manufacturing resources based on manufacturability features.

Sci Rep 2022 Jun 24;12(1):10775. Epub 2022 Jun 24.

College of Mechanical and Vehicle Engineering, Changchun University, Changchun, 130022, China.

Manufacturability evaluation is an effective way to shorten the development period, optimize manufacturing processes, and reduce product costs. The manufacturability of a product depends on the processing ability of specific manufacturing resources. The development of a manufacturing resources model serves as the foundation for manufacturability evaluation. To better utilize the information on manufacturing resources, this study adopted a hybrid approach by integrating the fuzzy c-means clustering algorithm and the genetic algorithm to group manufacturing resources based on manufacturing and geometric features. The information model of manufacturing resources was built by using the object-oriented method. Subsequently, the framework to evaluate manufacturing capability based on manufacturing resources was defined. Further, an application sample was exploited and its results were analyzed. The results of the subgroup showed that the hybrid algorithm was reliable and valid and helped improve the overall performance of the company chosen for this study. The proposed approach enhanced feasibility in decision-making and facilitated the management to make more informed decisions.
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http://dx.doi.org/10.1038/s41598-022-15072-2DOI Listing
June 2022

Identification of flexible Pif1-DNA interactions and their impacts on enzymatic activities.

Nucleic Acids Res 2022 Jun 24. Epub 2022 Jun 24.

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

Flexible regions in biomolecular complexes, although crucial to understanding structure-function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structure determination methods. Taking two Pif1 helicases (ScPif1 and BsPif1) as model systems, we found that, besides a few tightly bound nucleotides, adjacent solvent-exposed nucleotides interact dynamically with the helicase surfaces. The whole nucleotide segment possessed curved conformations and covered the two RecA-like domains of the helicases, which are essential for the inch-worm mechanism. The synergetic approach reveals that the interactions between the exposed nucleotides and the helicases could be reduced by large stretching forces or electrostatically shielded with high-concentration salt, subsequently resulting in reduced translocation rates of the helicases. The dynamic interactions between the exposed nucleotides and the helicases underlay the force- and salt-dependences of their enzymatic activities. The present single-molecule based approach complements high-resolution structural methods in deciphering the molecular mechanisms of the helicases.
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http://dx.doi.org/10.1093/nar/gkac529DOI Listing
June 2022

Upregulation of osteoprotegerin inhibits -butyl hydroperoxide-induced apoptosis of human chondrocytes.

Exp Ther Med 2022 Jul 26;24(1):470. Epub 2022 May 26.

Department of Joint Surgery, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China.

Necrosis of the femoral head (NFH) is an orthopedic disease characterized by a severe lack of blood supply to the femoral head and a marked increase in intraosseous pressure. NFH is associated with numerous factors, such as alcohol consumption and hormone levels. The present study focused on the expression levels of osteoprotegerin (OPG) in NFH and the effect of overexpression on chondrocyte apoptosis. The results demonstrated that expression was markedly decreased in the femoral head of patients with NFH compared with normal femoral heads. Lentivirus-mediated overexpression of in human chondrocytes reversed the decrease in cell viability and the increase in reactive oxygen species production induced by an oxidative stress-inducing factor, -butyl hydroperoxide. Flow cytometry and TUNEL assays revealed that overexpression inhibited the apoptosis of chondrocytes. In addition, it was revealed that exerted its anti-apoptotic effect mainly by promoting Bcl-2 expression and Akt phosphorylation and inhibiting caspase-3 cleavage and Bax expression. The present study revealed that may be an important regulator of NFH.
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http://dx.doi.org/10.3892/etm.2022.11397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204554PMC
July 2022

An Analysis of the Effect of Abrasive/Tool Wear on the Ductile Machining of Fused Silica from the Perspective of Stress.

Micromachines (Basel) 2022 May 25;13(6). Epub 2022 May 25.

Key Laboratory for Precision and Non-Traditional Machining Technology of Ministry of Education, School of Mechanical Engineering, Dalian University of Technology, Dalian 116024, China.

Understanding the influence mechanism of abrasive/tool wear on machining is the key to realize high-efficiency ultra-precision machining of fused silica. To explore the effect of abrasive/tool wear on ductile machining, the smoothed particle hydrodynamics (SPH) cutting models with different edge radii are established. Through the analysis of equivalent rake angle, hydrostatic pressure, cutting force and maximum principal stress with the Flamant's formula, the influence of edge radii on ductile-brittle transition (DBT) is discussed for the first time. The simulation results show that when the edge radius increases from less to larger than the cutting depth, the equivalent rake angle changes from positive to negative, and the maximum hydrostatic pressure gradually increases, which is beneficial to promote the ductile processing. Meanwhile, with the rise of edge radius (i.e., abrasive/tool wear), both the cutting force and crack initiation angle increase, while the friction coefficient and normalized maximum principal decrease. When the value of normalized maximum principal stress exceeds 2.702, the crack in the workpiece begins to initiate, and its initiation angle calculated by the Flamant's formula is in good agreement with the simulation results as well as less than 50°. Finally, the nano-scratch experiment was carried out, and the material removal mechanism and friction coefficient similar to the simulation were obtained, which further proved the accuracy of SPH model. This study is meaningful for understanding the effect of abrasive/tool wear on the removal mechanism of brittle materials and improving the quality and efficiency of cutting and grinding.
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http://dx.doi.org/10.3390/mi13060820DOI Listing
May 2022

Characterization of Quality Properties in Spoiled Mianning Ham.

Foods 2022 Jun 11;11(12). Epub 2022 Jun 11.

Key Lab of Meat Processing of Sichuan Province, Chengdu University, Chengdu 610106, China.

Deep spoilage is a cyclical and costly problem for the meat industry. Mianning ham is a famous dry-cured meat product in Sichuan, China. The aim of this work was to investigate the physicochemical characteristics, sources of odor, and associated microorganisms that cause spoilage of Mianning ham. High-throughput sequencing and solid-phase microextraction-gas-chromatography (SPME-GC-MS) techniques were used to characterize the physicochemical properties, microbial community structure, and volatile compounds of spoiled Mianning ham and to compare it with normal Mianning ham. The results showed that spoiled ham typically had higher moisture content, water activity (a), and pH, and lower salt content. The dominant bacterial phylum detected in deeply spoiled ham was Firmicutes (95.4%). The dominant bacterial genus was (92.01%), the dominant fungal phylum was Ascomycota (98.48%), and the dominant fungal genus was (84.27%). A total of 57 volatile flavor substances were detected in deeply spoiled ham, including 11 aldehydes, 2 ketones, 6 alcohols, 10 esters, 20 hydrocarbons, 6 acids, and 2 other compounds. Hexanal (279.607 ± 127.265 μg/kg) was the most abundant in deeply spoiled ham, followed by Butanoic acid (266.885 ± 55.439 μg/kg) and Nonanal (165.079 ± 63.923 μg/kg). promoted the formation of five main flavor compounds, Heptanal, (E)-2-Octenal, 2-Nonanone, Hexanal, and Nonanal, in deeply spoiled ham by correlation analysis of microbial and volatile flavor substances.
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http://dx.doi.org/10.3390/foods11121713DOI Listing
June 2022

Genome-Wide Identification and Expression Analysis of Expansin Gene Family in the Storage Root Development of Diploid Wild Sweetpotato .

Genes (Basel) 2022 Jun 10;13(6). Epub 2022 Jun 10.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.

Expansins play important roles in root growth and development, but investigation of the expansin gene family has not yet been reported in , and little is known regarding storage root (SR) development. In this work, we identified a total of 37 () in our previously reported SR-forming strain Y22 genome, which included 23 , 4 , 2 and 8 . The phylogenetic relationship, genome localization, subcellular localization, gene and protein structure, promoter -regulating elements, and protein interaction network were systematically analyzed to reveal the possible roles of in the SR development of . The gene expression profiling in Y22 SR development revealed that and were down-regulated, and were up-regulated while were not obviously changed during the critical period of SR expansion, and might be beneficial to SR development. Combining the tissue-specific expression in young SR transverse sections of Y22 and sweetpotato tissue, we deduced that , and might be the key genes for initial SR formation and enlargement, and might be the key gene for root growth and development. This work provides new insights into the functions of the expansin gene family members in , especially for and subfamilies genes in SR development.
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http://dx.doi.org/10.3390/genes13061043DOI Listing
June 2022

Adversarial Data Hiding in Digital Images.

Entropy (Basel) 2022 May 25;24(6). Epub 2022 May 25.

College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

In recent studies of generative adversarial networks (GAN), researchers have attempted to combine adversarial perturbation with data hiding in order to protect the privacy and authenticity of the host image simultaneously. However, most of the studied approaches can only achieve adversarial perturbation through a visible watermark; the quality of the host image is low, and the concealment of data hiding cannot be achieved. In this work, we propose a true data hiding method with adversarial effect for generating high-quality covers. Based on GAN, the data hiding area is selected precisely by limiting the modification strength in order to preserve the fidelity of the image. We devise a genetic algorithm that can explore decision boundaries in an artificially constrained search space to improve the attack effect as well as construct aggressive covert adversarial samples by detecting "sensitive pixels" in ordinary samples to place discontinuous perturbations. The results reveal that the stego-image has good visual quality and attack effect. To the best of our knowledge, this is the first attempt to use covert data hiding to generate adversarial samples based on GAN.
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http://dx.doi.org/10.3390/e24060749DOI Listing
May 2022

Emerging Roles of Microglia Depletion in the Treatment of Spinal Cord Injury.

Cells 2022 06 9;11(12). Epub 2022 Jun 9.

Senior Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100037, China.

Microglia, as the resident immune cells and first responder to neurological insults, play an extremely important role in the pathophysiological process of spinal cord injury. On the one hand, microglia respond rapidly and gather around the lesion in the early stage of injury to exert a protective role, but with the continuous stimulation of the injury, the excessive activated microglia secrete a large number of harmful substances, aggravate the injury of spinal cord tissue, and affect functional recovery. The effects of microglia depletion on the repair of spinal cord injury remain unclear, and there is no uniformly accepted paradigm for the removal methods and timing of microglia depletion, but different microglia depletion strategies greatly affect the outcomes after spinal cord injury. Therefore, this review summarizes the physiological and pathological roles of microglia, especially the effects of microglia depletion on spinal cord injury-sustained microglial depletion would aggravate injury and impair functional recovery, while the short-term depletion of microglial population in diseased conditions seems to improve tissue repair and promote functional improvement after spinal cord injury. Furthermore, we discuss the advantages and disadvantages of major strategies and timing of microglia depletion to provide potential strategy for the treatment of spinal cord injury.
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http://dx.doi.org/10.3390/cells11121871DOI Listing
June 2022

Cell graph neural networks enable the precise prediction of patient survival in gastric cancer.

NPJ Precis Oncol 2022 Jun 23;6(1):45. Epub 2022 Jun 23.

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, 3800, Australia.

Gastric cancer is one of the deadliest cancers worldwide. An accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the multiplexed immunohistochemistry (mIHC) images as Cell-Graphs, we propose a graph neural network-based approach, termed Cell-Graph Signature or CG, powered by artificial intelligence, for the digital staging of TME and precise prediction of patient survival in gastric cancer. In this study, patient survival prediction is formulated as either a binary (short-term and long-term) or ternary (short-term, medium-term, and long-term) classification task. Extensive benchmarking experiments demonstrate that the CG achieves outstanding model performance, with Area Under the Receiver Operating Characteristic curve of 0.960 ± 0.01, and 0.771 ± 0.024 to 0.904 ± 0.012 for the binary- and ternary-classification, respectively. Moreover, Kaplan-Meier survival analysis indicates that the "digital grade" cancer staging produced by CG provides a remarkable capability in discriminating both binary and ternary classes with statistical significance (P value < 0.0001), significantly outperforming the AJCC 8th edition Tumor Node Metastasis staging system. Using Cell-Graphs extracted from mIHC images, CG improves the assessment of the link between the TME spatial patterns and patient prognosis. Our study suggests the feasibility and benefits of such an artificial intelligence-powered digital staging system in diagnostic pathology and precision oncology.
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http://dx.doi.org/10.1038/s41698-022-00285-5DOI Listing
June 2022

Osteochondroma of the frist rib with pseudo hemangioma.

Asian J Surg 2022 Jun 20. Epub 2022 Jun 20.

Department of Orthopedic Trauma Surgery, Ningbo NO.6 Hospital, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.06.069DOI Listing
June 2022

Diagnostic accuracy of CCTA-derived versus angiography-derived quantitative flow ratio (CAREER) study: a prospective study protocol.

BMJ Open 2022 Jun 23;12(6):e055481. Epub 2022 Jun 23.

Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China

Introduction: Coronary CT angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is a novel non-invasive technology to assess the physiological significance of coronary stenoses, which enables fast and on-site computation of fractional flow reserve (FFR) from CCTA images. The objective of this investigator-initiated, prospective, single-centre clinical trial is to evaluate the diagnostic performance of CT-QFR with respect to angiography-derived QFR, using FFR as the reference standard.

Methods And Analysis: A total of 216 patients who have at least one lesion with a diameter stenosis of 30%-90% in an artery with ≥2.0 mm reference diameter will be enrolled in the study. FFR will be measured during invasive coronary angiography. CT-QFR and QFR will be assessed in two independent core laboratories in a blinded fashion. The primary endpoint is the diagnostic accuracy of CT-QFR in identifying haemodynamically significant coronary stenosis with FFR as the reference standard. The major secondary endpoint is the non-inferiority of CT-QFR compared with QFR in the patients without extensively calcified lesions.

Ethics And Dissemination: The study was approved by the Ethics Committee of Huadong Hospital Affiliated to Fudan University (2020K192). Outcomes will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.

Trial Registration Number: NCT04665817.
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http://dx.doi.org/10.1136/bmjopen-2021-055481DOI Listing
June 2022

Alkaline Phosphatase Electrochemical Micro-Sensor Based on 3D Graphene Networks for the Monitoring of Osteoblast Activity.

Biosensors (Basel) 2022 Jun 13;12(6). Epub 2022 Jun 13.

State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.

Alkaline phosphatase (ALP) is a significant biomarker that indicates osteoblast activity and skeletal growth. Efficient ALP detection methods are essential in drug development and clinical diagnosis. In this work, we developed an in-situ synthesized three-dimensional graphene networks (3DGNs)-based electrochemical sensor to determine ALP activity. The sensor employs an ALP enzymatic conversion of non-electroactive substrate to electroactive product and presents the ALP activity as an electrochemical signal. With 3DGNs as the catalyst and signal amplifier, a sample consumption of 5 μL and an incubation time of 2 min are enough for the sensor to detect a wide ALP activity range from 10 to 10,000 U/L, with a limit of detection of 5.70 U/L. This facile fabricated sensor provides a quick response, cost-effective and non-destructive approach for monitoring living adherent osteoblast cell activity and holds promise for ALP quantification in other biological systems and clinical samples.
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http://dx.doi.org/10.3390/bios12060406DOI Listing
June 2022

Biodegradable Zn-Cu-Fe Alloy as a Promising Material for Craniomaxillofacial Implants: An Investigation into Degradation Behavior, Cytotoxicity, and Hemocompatibility.

Front Chem 2022 6;10:860040. Epub 2022 Jun 6.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Zinc-based nanoparticles, nanoscale metal frameworks and metals have been considered as biocompatible materials for bone tissue engineering. Among them, zinc-based metals are recognized as promising biodegradable materials thanks to their moderate degradation rate ranging between magnesium and iron. Nonetheless, materials' biodegradability and the related biological response depend on the specific implant site. The present study evaluated the biodegradability, cytocompatibility, and hemocompatibility of a hot-extruded zinc-copper-iron (Zn-Cu-Fe) alloy as a potential biomaterial for craniomaxillofacial implants. Firstly, the effect of fetal bovine serum (FBS) on degradation behavior was evaluated. Furthermore, an extract test was used to evaluate the cytotoxicity of the alloy. Also, the hemocompatibility evaluation was carried out by a modified Chandler-Loop model. The results showed decreased degradation rates of the Zn-Cu-Fe alloy after incorporating FBS into the medium. Also, the alloy exhibited acceptable toxicity towards RAW264.7, HUVEC, and MC3T3-E1 cells. Regarding hemocompatibility, the alloy did not significantly alter erythrocyte, platelet, and leukocyte counts, while the coagulation and complement systems were activated. This study demonstrated the predictable degradation behavior, acceptable cytotoxicity, and appropriate hemocompatibility of Zn-Cu-Fe alloy; therefore, it might be a candidate biomaterial for craniomaxillofacial implants.
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http://dx.doi.org/10.3389/fchem.2022.860040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208203PMC
June 2022

Spatial Bridge Locking Fixator versus Traditional Locking Plates in Treating AO/OTA 32-A3.2 Fracture: Finite Element Analysis and Biomechanical Evaluation.

Orthop Surg 2022 Jun 22. Epub 2022 Jun 22.

Department of Orthopaedics, First Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, China.

Objective: To compare the biomechanical behaviors of the spatial bridge locking fixator (SBLF), single locking plate (SP), and double locking plate (DP) for AO/OTA 32-A3.2 fractures using finite element analysis and biomechanical tests.

Methods: Axial loading of 700 N was conducted on the AO/OTA 32-A3.2 model via finite element analysis. The von Mises stress and the interfragmentary movement (IFM) were comparatively analyzed in the three configurations above. On the mechanical tester, axial and torsional loading of 30 synthetic femurs (five specimens of each configuration for each test at random) was performed, and the interfragmentary movement, torsion angle, stiffness, and ultimate load were recorded and analyzed.

Results: The finite element analysis (FEA) results showed that the von Mises stress of the spatial bridge locking fixator (SBLF) was lower than that of the single locking plate (SP) and higher than that of the double locking plate (DP). At 700 N, the axial IFMs were 0.15-0.38 mm (SBLF), 0.03-0.84 mm (SP), and 0.02-0.07 mm (DP). The biomechanical experiment indicated that the axial interfragmentary movements (IFMs) were 0.44 ± 0.23 mm (SBLF), 1.02 ± 0.40 mm (SP), and 0.07 ± 0.07 mm (DP) (p < 0.001). The axial IFM of the SBLF group had the highest probability (79.26%) of falling within the ideal range (0.2-0.8 mm), and the SP and DP groups had probabilities of 27.10% and 3.14%, respectively. The axial stiffness in the SBLF group (1586 ± 130 N/mm) was significantly lower than that in the DP group (10,264 ± 2671 N/mm) (p < 0.001) but greater than that in the SP group (725 ± 178 N/mm) (p = 0.396). The range of axial loads to ultimate failure was 3385-4527 N (SBLF), 3377-4664 N (SP), and 3780-4804 N (DP). The shear motion of the fracture end was 0.35 ± 0.14 mm (SBLF), 0.16 ± 0.10 mm (SP), and 0.08 ± 0.04 mm (DP) (p < 0.001). The torsional stiffness was 1.68 ± 0.14 Nm/degree (SBLF), 2.32 ± 0.29 Nm/degree (SP) (SBLF&SP, p < 0.001), and 3.53 ± 0.73 Nm/degree (DP) (SBLF&DP, p < 0.001).

Conclusions: The SBLF structure may exhibit a better biomechanical performance compared with the SP and DP in providing the best quantity and more symmetrical interfragmentary movement for AO/OTA 32-A3.2 fractures.
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http://dx.doi.org/10.1111/os.13308DOI Listing
June 2022

[Clinical characteristics and cost-effectiveness of intramedullary nail and plate for the treatment of open tibial fractures].

Zhongguo Gu Shang 2022 Jun;35(6):512-20

The Second Department of Orthopaedics, Luonan County Hospital, Shangluo 726100, Shaanxi, China.

Objective: To analyze clinical characteristics and cost-effectiveness of different final surgical options for treating patients with open tibial fractures.

Methods: A retrospective analysis was conducted by enrolling 55 surgically treated patients with open tibial fractures from January 2018 to June 2019. All the patients were categorized in intramedullary nailing (IMN) group and locking compression plate(LCP) group according to the final fixation option. There were 35 cases in group IMN including 27 males and 8 females, aged from 25 to 69 years old with an average of (49.0±10.6) years old. Based on Gustilo-Anderson classification, there were 1 case of typeⅠ, 19 cases of typeⅡand 15 cases of type Ⅲ. There were 20 cases in group LCP including 15 males and 5 females, aged from 46 to 72 years old with an average age of (53.4±14.7) years old. Based on Gustilo-Anderson classification, there were 2 cases of typeⅠ, 11 cases of typeⅡand 7 cases of type Ⅲ. Preoperative waiting time, surgical debridement times, intraoperative bleeding loss, blood and albumin transfusion, operation time, bacterial cultures and complications, bone union time, Johner-Wruhs criteria at 1 year after operation and total cost within 1 year after surgery between two groups were compared. The variables recorded between two groups were statistically analyzed and compared respectively, then the factors affecting hospital costs were evaluated by univariate and multiple linear regression analysis respectively, finally the cost-effectiveness analysis was performed.

Results: Total 55 patients were enrolled with an average follow-up time of(16.4±7.1) months ranged from 14 to 27 months postoperatively. There were no significantly statistical differences of the demographic materials between the two groups. The intraoperative bleeding loss were(243.18±118.82) ml and (467.86±490.53) ml respectively in group IMN and LCP, the significantly statistical difference was discovered(<0.05). The surgical duration were(247.50±57.94) min and(350.00±178.77) min respectively in group IMN and LCP, the significantly statistical difference was discovered(<0.05). There were no significantly statistical differences of the average days before operation, surgical debridement times, received blood and albumin transfusion, wound cultures, complications and bone union time between the two groups(>0.05). The univariate analysis of the factors affecting the hospital costs indicated that patients with smoke or alcohol (=0.042), high energy damage (=0.012), patients with comorbidity diseases(=0.045), surgical debridement over 2 times (=0.001), intraoperative bleeding loss over 400 ml (<0.001), blood and albumin transfusion (=0.027), wound cultures (=0.000) and complications (=0.035) were the factors. The multiple linear regression analysis demonstrated the smoke or alcohol using[=-0.256, =-2.628, 95%CI(-29 667.09, -4 997.47), =0.014] was the only factor affecting the total cost. The excellent and good rate were 80% and 85% respectively based on the Johner-Wruhs criteria. The average total cost within 1 year after surgery was (136 435.90±39 093.98) CNY in group IMN and (140 034.62±56 821.12) CNY in group LCP. The total surgical duration and total intraoperative bleeding loss were significant lower in group IMN than in group LCP. The average total costs of was significantly higher. The average cost for every 1% of excellent and good rate was 1 705.45 CNY in group IMN and 1 647.46 CNY in group LCP. Each 1% increasing of excellent and good rate cost 719.74 CNY more in group LCP compared with group IMN.

Conclusion: Both IMN and LCP could provide a satisfactory outcome for open tibial fractures. Meanwhile considering the total cost, patients with smoke or alcohol history, traffic accident, comorbidity diseases, surgical debridement over 2 times, intraoperative bleeding loss over 400 ml, and complications should not be ignored.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.06.003DOI Listing
June 2022

Comment on Yang et al., Development of a monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for detection of H7N9 subtype avian influenza virus. J Med Virol. 2021; 93:3939-3943.

Authors:
Ming Li Tianfei Yu

J Med Virol 2022 Jun 21. Epub 2022 Jun 21.

Heilongjiang Provincial Key Laboratory of Resistance Gene Engineering and Protection of Biodiversity in Cold Areas, Qiqihar, China.

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http://dx.doi.org/10.1002/jmv.27950DOI Listing
June 2022

Heavy metals in marine food web from Laizhou Bay, China: Levels, trophic magnification, and health risk assessment.

Sci Total Environ 2022 Jun 18;841:156818. Epub 2022 Jun 18.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

Heavy metals in ocean may accumulate in seafood through food web and pose risks to human health. This study investigated the occurrence, trophic magnification, and health risks of 7 heavy metals in 20 marine organisms (n = 222) in Laizhou Bay (LZB), China. Results showed that Zn was the most abundant metal, followed by Cu, As, Cd, Cr, Ni and Pb. The total concentrations of 7 heavy metals in the organisms ranked in the order of crab ˃ shellfish ˃ algae ˃ fish ˃ starfish. Interspecific differences were found in the concentrations of Cr, Ni, Cu and Cd in marine organisms from LZB. Crab and shellfish showed much higher enrichment ability of heavy metals than that of algae, starfish and fish. Cd is the most biological accumulated element with the mean biota-sediment accumulation factor (BSAF) of 12.9. Stable isotope analysis showed a significant difference of δN among these five species (p < 0.01), and a food web was constructed accordingly. A biodilution pattern was found for Pb, As and Ni and no trophic interference in metal uptake was observed for Zn, Cu, Ni and Cr in the food web of LZB. The estimated daily intake (EDI) and target hazard quotients (THQs) of As and Cd indicated an adverse health effect on consumption of the seafood. The mean lifetime cancer risks (LCRs) for Cd and As suggested a potential carcinogenic effect on consumption of these seafood. This study provides a basis for health risk assessment of heavy metals in marine foods.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156818DOI Listing
June 2022

Spatial distribution and risk assessment of certain antibiotics in 51 urban wastewater treatment plants in the transition zone between North and South China.

J Hazard Mater 2022 Jun 7;437:129307. Epub 2022 Jun 7.

College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, PR China.

The release of antibiotics from WWTPs into the environment has raised increasing concern worldwide. The monitoring of antibiotics in WWTPs throughout a region is crucial for emerging pollutant management. A large-scale survey of the occurrence, distribution, and ecological risk of seven antibiotics in 51 WWTPs was conducted in Shaanxi Province, China. Norfloxacin and ofloxacin had the highest detection concentrations of 474.2 and 656.18 ng L, respectively. Antibiotic residues in effluents were decreased by 5.88-94.16 % after different treatment processes. In particular, AO or mixed processes performed well in removing target antibiotic compounds simultaneously. The ecological risk posed by antibiotic compounds detected in effluents was calculated using the risk quotient (RQ). Norfloxacin, ofloxacin, tetracycline, and roxithromycin posed different levels of potential ecotoxicological risk (RQ = 0.02-7.59). Based on the sum of the RQ values of individual antibiotic compounds, each investigated WWTP showed potential ecological risk. WWTPs with high risk levels were mainly found in the central region, while those in the southern region exhibited low risk levels, and those in the northern region showed risk levels between medium and high. This comprehensive investigation provides promising results to support the safe use and control of antibiotics in the study area.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129307DOI Listing
June 2022

Observation of Heavy-Chain C-Terminal Amidation in Human Endogenous IgG.

J Pharm Sci 2022 Jun 16. Epub 2022 Jun 16.

Process Development, Amgen Inc. One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address:

Therapeutic IgG mAbs expressed from Chinese hamster ovary (CHO) cells are known to contain three C-terminal variants in their heavy chains, namely, the unprocessed C-terminal lysine, the processed C-terminal lysine, and C-terminal amidation. Although the presence of C-terminal amidation in CHO-expressed IgGs is well studied, the biological impact of the variant on the safety and efficacy of biotherapeutics has not been well understood. To further our biological understanding of C-terminal amidation, we analyzed a series of IgG samples, including both endogenous human IgGs as well as recombinant IgGs of different subclasses expressed from both CHO and murine cell lines, for their heavy-chain C-terminal variants by LC-MS/MS based peptide mapping. The results demonstrate that heavy-chain C-terminal amidation is a common variant occurring in IgG of all four subclasses (IgG1, IgG2, IgG3 and IgG4). The variant is generally present in recombinant IgG mAbs expressed from CHO cell lines but not in IgG mAbs expressed from murine cell lines, whereas the IgGs expressed from murine cell lines contain a much larger amount of unprocessed C-terminal lysine. Additionally, a significant amount of heavy-chain C-terminal amidation is observed in endogenous human IgGs, indicating that small amount of the variant present in therapeutic IgGs does not pose a safety concern.
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http://dx.doi.org/10.1016/j.xphs.2022.06.012DOI Listing
June 2022

Scientometric analysis and scientific trends on microplastics research.

Chemosphere 2022 Oct 14;304:135337. Epub 2022 Jun 14.

Department of Materials Engineering, KU Leuven, Leuven, 3001, Belgium.

In recent years, the environmental pollution of microplastics has attracted much attention. To date, there have been a lot of researches on microplastics and a series of studies published. In this study, by bibliometric analysis method to evaluated the development and evolution on microplastics research trends and hot spots. A total of 2872 literature information was collected from the Web of Science (2004-2020), which was used for bibliometric visual analysis by CiteSpace. It was possible to see the contributing countries, institutions, authors, keywords, and future study directions in the microplastics sectors by looking at the visual representation of the results. (1) Since 2004, scientific advancements in this sector have advanced significantly, with a significant increase in speed since 2012. (2) China and the United States are the world's leading researchers in microplastics. (3) The study of microplastics was multidisciplinary, comprising researchers from the fields of ecology, chemistry, molecular biology, environmental science, and oceanography. (4) In recent years, researchers have concentrated their attention on the distribution and toxicity of microplastics in the environment, as well as their coupled pollution with heavy metal contaminants. In conclusion microplastics study in environmental science has become increasingly popular in recent years. Topics include dispersion, toxicity, and coupled pollution with heavy metal pollutants. Researchers in a wide range of fields are involved in microplastics research. Furthermore, policies and regulations about microplastics in global were summarized, and membrane technology has potential to remove microplastics from water. The above findings help to clearly grasp the content and development trend of microplastics research, point out the future research direction for scholars, and promote microplastics research and pollution prevention and control.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135337DOI Listing
October 2022

Ejiao ameliorates lipopolysaccharide-induced pulmonary inflammation via inhibition of NFκB regulating NLRP3 inflammasome and mitochondrial ROS.

Biomed Pharmacother 2022 Aug 14;152:113275. Epub 2022 Jun 14.

Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

There is no effective treatment for acute lung injury (ALI) at present. Some studies have reported the anti-inflammatory effect of Ejiao, but no study has addressed the underlying action mechanism. In this study, the CCK8 assay displayed Ejiao had a protective effect against LPS-elicited inflammatory lung epithelial Beas 2B cells (LILEB 2B cells). Beas 2B cells treated with LPS and Ejiao were challenged with NFκB inhibitor Bay11-7082 and ROS scavenger N-acetyl cysteine (NAC) alone and in combination. The results of qRT-PCR, Western blotting and fluorescence labeling experiments using Bay11-7082 and NAC demonstrated Ejiao could significantly decrease the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β related to pyroptosis of LILEB 2B cells. Moreover, Ejiao reduced the production of mitochondrial ROS and reversed the change of mitochondrial membrane potential of LILEB 2B cells. Then, HE staining demonstrated Ejiao had a protective effect against the LPS-elicited ALI mouse model (LAMM). Ejiao also dramatically decreased the cell amount and the overall protein concentration of bronchoalveolar lavage fluid in LAMM. Immunohistochemical staining showed Ejiao remarkably reduced the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β. The ELISA of IL-1β revealed Ejiao could dose-dependably decrease the concentration of IL-1β in lung tissues, serum and BALF of LAMM. Finally, fluorescence labeling demonstrated Ejiao significantly reduced the mitochondrial ROS generation in the lung tissue of LAMM. This finding may afford a novel strategy for the precaution and therapy of ALI.
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http://dx.doi.org/10.1016/j.biopha.2022.113275DOI Listing
August 2022
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