Publications by authors named "Yi Cao"

829 Publications

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics.

Phytother Res 2022 Jan 27. Epub 2022 Jan 27.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.
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http://dx.doi.org/10.1002/ptr.7395DOI Listing
January 2022

Guest Molecule-Mediated Energy Harvesting in a Conformationally Sensitive Peptide-Metal Organic Framework.

J Am Chem Soc 2022 Jan 24. Epub 2022 Jan 24.

Department of Molecular Microbiology and Biotechnology, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 6997801, Israel.

The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.
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http://dx.doi.org/10.1021/jacs.1c11750DOI Listing
January 2022

Silencing Inhibits the Proliferation and Metastasis of Gastric Cancer.

J Cancer 2022 1;13(2):565-578. Epub 2022 Jan 1.

Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, China.

RNF114 (E3 ubiquitin ligase RING finger protein 114) was first identified as a zinc-binding protein that promotes psoriasis development; however, its role in gastric cancer is still unclear. We explored the relationship between and gastric cancer using bioinformatics and molecular biology techniques. The results showed that RNF114 was highly expressed in gastric cancer and negatively correlated with the patient's prognosis. Functional assays suggested that silencing suppressed the proliferation and metastasis of gastric cancer cells to a certain extent. Further studies showed that expression was potentially targeted by miR-218-5p and methylation modification, and mediated downstream EGR1 (early growth response 1) degradation by the ubiquitylation approach. Together, the present results highlight the detrimental effects of overexpression in gastric cancer and contribute to a better understanding of the mechanisms underlying functionality.
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http://dx.doi.org/10.7150/jca.62033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8771524PMC
January 2022

Multiple Protein Subcellular Locations Prediction Based on Deep Convolutional Neural Networks with Self-Attention Mechanism.

Interdiscip Sci 2022 Jan 23. Epub 2022 Jan 23.

School of Information Science and Engineering, Shandong Normal University, Jinan, China.

As an important research field in bioinformatics, protein subcellular location prediction is critical to reveal the protein functions and provide insightful information for disease diagnosis and drug development. Predicting protein subcellular locations remains a challenging task due to the difficulty of finding representative features and robust classifiers. Many feature fusion methods have been widely applied to tackle the above issues. However, they still suffer from accuracy loss due to feature redundancy. Furthermore, multiple protein subcellular locations prediction is more complicated since it is fundamentally a multi-label classification problem. The traditional binary classifiers or even multi-class classifiers cannot achieve satisfactory results. This paper proposes a novel method for protein subcellular location prediction with both single and multiple sites based on deep convolutional neural networks. Specifically, we first obtain the integrated features by simultaneously considering the pseudo amino acid, amino acid index distribution, and physicochemical property. We then adopt deep convolutional neural networks to extract high-dimensional features from the fused feature, removing the redundant preliminary features and gaining better representations of the raw sequences. Moreover, we use the self-attention mechanism and a customized loss function to ensure that the model is more inclined to positive data. In addition, we use random k-label sets to reduce the number of prediction labels. Meanwhile, we employ a hybrid strategy of over-sampling and under-sampling to tackle the data imbalance problem. We compare our model with three representative classification alternatives. The experiment results show that our model achieves the best performance in terms of accuracy, demonstrating the efficacy of the proposed model.
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http://dx.doi.org/10.1007/s12539-021-00496-7DOI Listing
January 2022

A low-swelling and toughened adhesive hydrogel with anti-microbial and hemostatic capacities for wound healing.

J Mater Chem B 2022 Jan 20. Epub 2022 Jan 20.

CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Hydrogel-based wound dressings with tissue adhesion abilities are widely used for wound closure. However, currently developed hydrogel adhesives are still poor at continuing to seal wounds while bleeding is ongoing. Herein, we demonstrate an antibacterial and hemostatic hydrogel adhesive with low-swelling properties and toughness for wound healing. The hydrogel was composed of Pluronic F127 diacrylate, quaternized chitosan diacrylate, silk fibroin, and tannic acid, and it was not only able to maintain good tissue adhesion abilities in a moist environment but it also showed guaranteed tissue adhesion and mechanical strength after absorbing water due to its low-swelling and toughness properties. Furthermore, and tests demonstrated that the hydrogel also had antibacterial, antioxidant, and hemostatic properties, which could promote tissue regeneration. All these findings demonstrate that this hydrogel with multifunctional properties is a promising material for clinical wound healing applications.
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http://dx.doi.org/10.1039/d1tb01871jDOI Listing
January 2022

Covalent Biosensing Polymer Chain Reaction Enabling Periphery Blood Testing to Predict Tumor Invasiveness with a Platelet Procancerous Protein.

Anal Chem 2022 Jan 17. Epub 2022 Jan 17.

School of Biological Science and Technology, University of Jinan, Jinan 250024, China.

Periphery blood testing is an attractive and relatively less invasive way of early cancer screening. In this work, based on the latest understanding of the pivotal role of platelets in promoting cancer invasion, a method for detecting a procancerous protein overexpressed both on platelets and in cancer cells is developed. As a kinase, the enzymatic activity, abundance, and self-phosphorylation of this protein are all important factors influencing its procancerous activity. To simultaneously determine these three important biochemical parameters, electrochemical control is called upon to connect or disconnect a polymer chain reaction (PCR) primer with a small-molecule synthetic probe, and with the target protein, in a target-specific manner. The resulting PCR signal amplification greatly improves the sensitivity of the design and also enables direct detection of the protein and its catalytic activity as well as its self-phosphorylation in clinical periphery blood samples from hepatocellular carcinoma (HCC) patients. This may point to future application of the proposed method in the early screening of HCC to assist its diagnosis and treatment.
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http://dx.doi.org/10.1021/acs.analchem.1c03349DOI Listing
January 2022

Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure.

Mol Biol Rep 2022 Jan 15. Epub 2022 Jan 15.

Department of Reproductive Medical Center, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, China.

Background: Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity.

Methods And Results: Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion.

Conclusion: These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.
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http://dx.doi.org/10.1007/s11033-021-06979-6DOI Listing
January 2022

Artificially created interfacial states enabled van der Waals heterostructure memory device.

Nanotechnology 2022 Jan 13. Epub 2022 Jan 13.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, SINGAPORE.

Two-dimensional (2D) interface plays a predominate role in determining the performance of a device that is configured as a van der Waals heterostructure (vdWH). Intensive efforts have been devoted to suppressing the emergence of interfacial states during vdWH stacking process, which facilitates the charge interaction and transfer between the heterostructure layers. However, the effective generation and modulation of the vdWH interfacial states could give rise to a new design and architecture of 2D functional devices. Here, we report a 2D non-volatile vdWH memory device enabled by the artificially created interfacial states between hexagonal boron nitride (hBN) and molybdenum ditelluride (MoTe2). The memory originates from the microscopically coupled optical and electrical responses of the vdWH, with the high reliability reflected by its long data retention time over 10^4 s and large write-erase cyclic number exceeding 100. Moreover, the storage currents in the memory can be precisely controlled by the writing and erasing gates, demonstrating the tunability of its storage states. The vdWH memory also exhibits excellent robustness with wide temperature endurance window from 100 K to 380 K, illustrating its potential application in harsh environment. Our findings promise interfacial-states engineering as a powerful approach to realize high performance vdWH memory device, which opens up new opportunities for its application in 2D electronics and optoelectronics.
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http://dx.doi.org/10.1088/1361-6528/ac4b2fDOI Listing
January 2022

Slide-Ring Structure-Based Double-Network Hydrogel with Enhanced Stretchability and Toughness for 3D-Bio-Printing and Its Potential Application as Artificial Small-Diameter Blood Vessels.

ACS Appl Bio Mater 2021 Dec 28;4(12):8597-8606. Epub 2021 Nov 28.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China.

Artificial small-diameter blood vessels (SDBVs) are extremely limited in their thrombosis and still present significant clinical challenges worldwide. In recent years, 3D-bio-printing has offered a powerful technique to fabricate vessel channels in tissue engineering applications. Hydrogels are attractive bio-inks for SDBVs 3D-bio-printing, but they usually present weak mechanical properties. To overcome the weak mechanical properties of hydrogel bio-inks, a printable human umbilical vein endothelial cell (HUVEC)-laden polyrotaxane-alginate (PR-Alg) double-network (DN) hydrogel was fabricated. The PR-Alg DN hydrogel consists of a Ca cross-linked alginate network to form the first network rapidly, and a photo-cross-linked slide-ring network was designed as the second network. By combining special hydrogel structures of slide-ring (SR) and double network (DN), we significantly improved the mechanical properties of hydrogels. The PR-Alg DN hydrogel provides excellent stress (199 ± 20 kPa) and strain (1239 ± 58%), and the fracture energy reaches 668 ± 80 J/m. Additionally, due to the presence of biocompatible materials and the gentle 3D-bio-printing process, the 3D-bio-printed channels showed outstanding biocompatibility, particularly in HUVECs' survival and proliferation. We anticipate that this work will expand the application of hydrogels with improved mechanical properties in biomedicine, particularly for artificial SDBVs.
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http://dx.doi.org/10.1021/acsabm.1c01052DOI Listing
December 2021

Low-cost and easy-fabrication lightweight drivable electrode array for multiple-regions electrophysiological recording in free-moving mice.

J Neural Eng 2022 Jan 24;19(1). Epub 2022 Jan 24.

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institution, Shenzhen, 518055, People's Republic of China.

Extracellular electrophysiology has been widely applied to neural circuit dissections. However, long-term multiregional recording in free-moving mice remains a challenge. Low-cost and easy-fabrication of elaborate drivable electrodes is required for their prevalence.A three-layer nested construct (outside diameter, OD ∼ 1.80 mm, length ∼10 mm, <0.1 g) was recruited as a drivable component, which consisted of an ethylene-vinyl acetate copolymer heat-shrinkable tube, non-closed loop ceramic bushing, and stainless ferrule with a bulge twining silver wire. The supporting and working components were equipped with drivable components to be assembled into a drivable microwire electrode array with a nested structure (drivable MEANS). Two drivable microwire electrode arrays were independently implanted for chronic recording in different brain areas at respective angles. An optic fiber was easily loaded into the drivable MEANS to achieve optogenetic modulation and electrophysiological recording simultaneously.The drivable MEANS had lightweight (∼0.37 g), small (∼15 mm × 15 mm × 4 mm), and low cost (⩽$64.62). Two drivable MEANS were simultaneously implanted in mice, and high-quality electrophysiological recordings could be applied ⩾5 months after implantation in freely behaving animals. Electrophysiological recordings and analysis of the lateral septum (LS) and lateral hypothalamus in food-seeking behavior demonstrated that our drivable MEANS can be used to dissect the function of neural circuits. An optical fiber-integrated drivable MEANS (∼0.47 g) was used to stimulate and record LS neurons, which suggested that changes in working components can achieve more functions than electrophysiological recordings, such as optical stimulation, drug release, and calcium imaging.Drivable MEANS is an easily fabricated, lightweight drivable microwire electrode array for multiple-region electrophysiological recording in free-moving mice. Our design is likely to be a valuable platform for both current and prospective users, as well as for developers of multifunctional electrodes for free-moving mice.
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http://dx.doi.org/10.1088/1741-2552/ac494eDOI Listing
January 2022

Characterization of the complete mitochondrial genome of (Ellis & Everh, 1893) (Dothideomycetes: Capnodiales).

Mitochondrial DNA B Resour 2022 28;7(1):130-131. Epub 2021 Dec 28.

Plant Protection Division, Guizhou Academy of Tobacco Science, Guiyang, P. R. China.

The mitochondrial genome of the fungal pathogen was sequenced for the first time using a combination of Illumina and Nanopore sequencing technologies. The circular genome is 27,737 bp in length with G + C content of 27.43%, consisting of 15 protein-coding genes, 26 transfer RNA genes and 2 ribosomal RNA genes. Phylogenetic analysis shows that the mtDNA is closely related to .
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http://dx.doi.org/10.1080/23802359.2021.2013745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725932PMC
December 2021

Development and validation of an early predictive nomogram for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Ann Transl Med 2021 Nov;9(22):1664

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Previous studies have shown that platelet is involved in the occurrence and progression of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), but the relationship between platelet and DCI is not completely clear. Here, we aimed to screen the early platelet parameters associated with DCI after aSAH and develop an early predictive nomogram for DCI after aSAH.

Methods: The study was carried out in the neurosurgery department of Affiliated Hospital of North Sichuan Medical College. A total of 285 consecutive aSAH patients admitted within 24 hours after onset were analyzed retrospectively. Univariate and multivariate analyses were used to identify risk factors for DCI. A predictive nomogram was developed and validated with R software.

Results: Sixty-six (23.16%) of the 285 patients with aSAH exhibited DCI during hospitalization. The DCI group and the non-DCI group showed statistically significant differences in red blood cell count (RBC), platelet count (PLT), mean platelet volume (MPV), modified Fisher grade and platelet distribution width (PDW). Multivariable logistic regression analysis showed that modified Fisher grade [odds ratio (OR) =1.354; 95% confidence interval (CI): 1.034-1.773; P=0.028] and mean MPV [OR =1.825; 95% CI: 1.429-2.331; P<0.001] were independent risk factors for DCI. Modified Fisher grade, RBC, PLT, MPV, and PDW were used to develop a predictive nomogram for DCI. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.799 (95% CI: 0.737-0.861) in the training set and 0.783 (95% CI: 0.616-0.949) in the validation set. The calibration curve showed that the predicted probability concurred with the actual probability. Decision curve analysis indicated that this nomogram had good clinical application value and could be used for clinical decision making.

Conclusions: Our study found that MPV was an early predictor of DCI after aSAH. The nomogram incorporating early MPV had greater value in predicting DCI after aSAH.
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http://dx.doi.org/10.21037/atm-21-5200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667093PMC
November 2021

Quantitative evaluation of ankle cartilage in asymptomatic adolescent football players after season by T2-mapping magnetic resonance imaging.

Biomed Eng Online 2021 Dec 28;20(1):130. Epub 2021 Dec 28.

Department of Radiology, Tianjin Hospital, Tianjin University, #406 Jiefangnan Rd., HeXi district, Tianjin, 300299, People's Republic of China.

Background: Ankle sprain affects the structure and function of ankle cartilage. However, it is not clear whether the daily training and competition affect the ankle cartilage without acute injury. Changes in ankle cartilage without injury may influence future strategies to protect ankle function in athletes. This study aimed to evaluate whether the composition of ankle cartilage significantly altered in asymptomatic adolescent football players after a whole season of training and competition using T2-mapping magnetic resonance imaging (MRI).

Materials And Methods: 12 local club's U17 asymptomatic adolescent football players without abnormalities in routine MRI were included. Routine and T2-mapping MRI were performed to measure the cartilage thickness of tibiotalar joint (TT) and posterior subtalar joint (pST) and T2 values in pre- and post-seasons. All of them took the right side as dominant foot.

Results: In the pre- and post-seasons, cartilage T2 values in TT (talus side) and pST (calcaneus side) were higher than that of TT (tibial side) and pST (talus side) (all p < 0.05), which was caused by magic angle effect and gravity load. No statistically significant differences in thickness after season in the other cartilages of ankle were found compared with that before the season (all p > 0.05). However, T2 values of TT (tibial side and talus side) cartilage in the dominant foot were significantly reduced after season (p = 0.008; p = 0.034). These results indicate that the microstructure of articular cartilage changes in the joints with greater mobility, although no trauma occurred and the gross morphology of cartilage did not change.

Conclusion: Changes in the T2 values of tibiotalar joint cartilage in the dominant foot of healthy young athletes before and after the season suggest that the microstructure of cartilage had changed during sports even without injury. This finding suggests that the dominant ankle joint should be protected during football to delay degeneration of the articular cartilage.
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http://dx.doi.org/10.1186/s12938-021-00970-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713405PMC
December 2021

Transcriptomic-based toxicological investigations of graphene oxide with modest cytotoxicity to human umbilical vein endothelial cells: changes of Toll-like receptor signaling pathways.

Toxicol Res (Camb) 2021 Dec 16;10(6):1104-1115. Epub 2021 Oct 16.

Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.

The wide uses of graphene oxide (GO) lead to the contact of GO with vascular systems, so it is necessary to investigate the toxicological effects of GO to endothelial cells. Recently, we reported that GO of small lateral size (<500 nm) was relatively biocompatible to human umbilical vein endothelial cells (HUVECs), but recent studies by using omics-techniques revealed that nanomaterials (NMs) even without acute cytotoxicity might induce other toxicological effects. This study investigated the effects of GO on HUVECs based on RNA-sequencing and bioinformatics analysis. Even after exposure to 100 μg/ml GO, the cellular viability of HUVECs was higher than 70%. Furthermore, 25 μg/ml GO was internalized but did not induce ultrastructural changes or intracellular superoxide. These results combined indicated GO's relatively high biocompatibility. However, by analyzing the most significantly altered Gene Ontology terms and Kyoto Encyclopedia of Gene and Genomes pathways, we found that 25 μg/ml GO altered pathways related to immune systems' functions and the responses to virus. We further verified that GO exposure significantly decreased Toll-like receptor 3 and interleukin 8 proteins, indicating an immune suppressive effect. However, THP-1 monocyte adhesion was induced by GO with or without the presence of inflammatory stimulus lipopolysaccharide. We concluded that GO might inhibit the immune responses to virus in endothelial cells at least partially mediated by the inhibition of TLR3. Our results also highlighted a need to investigate the toxicological effects of NMs even without acute cytotoxicity by omics-based techniques.
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http://dx.doi.org/10.1093/toxres/tfab091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692726PMC
December 2021

Corrigendum to: A functional CNVR_3425.1 damping lincRNA FENDRR increases lifetime risk of lung cancer and COPD in Chinese.

Carcinogenesis 2021 Dec;42(12):1506-1507

The State Key Lab of Respiratory Disease, The institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China.

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http://dx.doi.org/10.1093/carcin/bgab105DOI Listing
December 2021

Biophysical Approaches for Applying and Measuring Biological Forces.

Adv Sci (Weinh) 2021 Dec 19:e2105254. Epub 2021 Dec 19.

Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210023, P. R. China.

Over the past decades, increasing evidence has indicated that mechanical loads can regulate the morphogenesis, proliferation, migration, and apoptosis of living cells. Investigations of how cells sense mechanical stimuli or the mechanotransduction mechanism is an active field of biomaterials and biophysics. Gaining a further understanding of mechanical regulation and depicting the mechanotransduction network inside cells require advanced experimental techniques and new theories. In this review, the fundamental principles of various experimental approaches that have been developed to characterize various types and magnitudes of forces experienced at the cellular and subcellular levels are summarized. The broad applications of these techniques are introduced with an emphasis on the difficulties in implementing these techniques in special biological systems. The advantages and disadvantages of each technique are discussed, which can guide readers to choose the most suitable technique for their questions. A perspective on future directions in this field is also provided. It is anticipated that technical advancement can be a driving force for the development of mechanobiology.
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http://dx.doi.org/10.1002/advs.202105254DOI Listing
December 2021

Nanoscale engineering of ring-mounted nanostructure around AAO nanopores for highly sensitive and reliable SERS substrates.

Nanotechnology 2022 Jan 5;33(13). Epub 2022 Jan 5.

School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, 100083, People's Republic of China.

Surface-enhanced Raman scattering (SERS) is recognized as one of the most favored techniques for enhancing Raman signals. The morphology of the SERS substrate profoundly affects molecular Raman spectra. This study aimed to construct a ring-mounted nanostructured substrate via liquid-liquid two-phase self-assembly incorporated with anodic aluminum oxide (AAO) membrane transfer techniques. High-density nanoparticles (NPs) assembled on AAO membranes were ascribed to reduce the diameters of the nanopores, with Au-Ag alloy NPs to regulate the dielectric constant so as to reveal the local surface plasmon resonance tunability. SERS engineered in this way allowed for the fabrication of a ring-mounted nanostructured substrate where the distribution density of NPs and dielectric constant could be independently fine-tuned. High SERS activity of the substrate was revealed by detecting the enhanced factor of crystal violet and rhodamine 6G molecules, which was up to 1.56 × 10. Moreover, SERS of thiram target molecules confirmed the supersensitivity and repeatability of the substrate as a practical application. The results of this study manifested a low-cost but high-efficiency ring-mounted nanostructured SERS substrate that might be suitable in many fields, including biosensing, medical research, environmental monitoring, and optoelectronics.
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http://dx.doi.org/10.1088/1361-6528/ac4355DOI Listing
January 2022

Hydrogel tapes for fault-tolerant strong wet adhesion.

Nat Commun 2021 12 9;12(1):7156. Epub 2021 Dec 9.

Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Key Laboratory of Intelligent Optical Sensing and Manipulation, Ministry of Education, Department of Physics, Nanjing University, 210093, Nanjing, China.

Fast and strong bio-adhesives are in high demand for many biomedical applications, including closing wounds in surgeries, fixing implantable devices, and haemostasis. However, most strong bio-adhesives rely on the instant formation of irreversible covalent crosslinks to provide strong surface binding. Repositioning misplaced adhesives during surgical operations may cause severe secondary damage to tissues. Here, we report hydrogel tapes that can form strong physical interactions with tissues in seconds and gradually form covalent bonds in hours. This timescale-dependent adhesion mechanism allows instant and robust wet adhesion to be combined with fault-tolerant convenient surgical operations. Specifically, inspired by the catechol chemistry discovered in mussel foot proteins, we develop an electrical oxidation approach to controllably oxidize catechol to catecholquinone, which reacts slowly with amino groups on the tissue surface. We demonstrate that the tapes show fast and reversible adhesion at the initial stage and ultrastrong adhesion after the formation of covalent linkages over hours for various tissues and electronic devices. Given that the hydrogel tapes are biocompatible, easy to use, and robust for bio-adhesion, we anticipate that they may find broad biomedical and clinical applications.
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http://dx.doi.org/10.1038/s41467-021-27529-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660897PMC
December 2021

Influences of Unmodified and Carboxylated Carbon Nanotubes on Lipid Profiles in THP-1 Macrophages: A Lipidomics Study.

Int J Toxicol 2022 Jan-Feb;41(1):16-25. Epub 2021 Dec 10.

Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.

Since the possible roles of surface modifications in determining multi-walled carbon nanotube (MWCNT)-promoted endoplasmic reticulum (ER) stress-mediated lipid-laden macrophage foam cell formation are still in debate, we compared unmodified and carboxylated MWCNT-induced cytotoxicity, lipid profile changes, and expression of ER stress genes in THP-1 macrophages. Particularly, we focused on lipid profile changes by using lipidomics approaches. We found that unmodified and carboxylated MWCNTs significantly decreased cellular viability and appeared to damage the cellular membrane to a similar extent. Likewise, the results from Oil Red O staining showed that both types of MWCNTs slightly but significantly induced lipid accumulation. In keeping with Oil Red O staining results, lipidomics data showed that both types of MWCNTs up-regulated most of the lipid classes. Interestingly, almost all lipid classes were relatively higher in carboxylated MWCNT-exposed THP-1 macrophages compared with unmodified MWCNT-exposed cells, indicating that carboxylated MWCNTs more effectively changed lipid profiles. But in contrast to our expectation, none of the MWCNTs significantly induced the expression of ER stress genes. Even, compared with carboxylated MWCNTs, unmodified MWCNTs induced higher expression of lipid genes, including macrophage scavenger receptor 1 and fatty acid synthase. Combined, our results suggested that even though carboxylation did not significantly affect MWCNT-induced lipid accumulation, carboxylated MWCNTs were more potent to alter lipid profiles in THP-1 macrophages, indicating the need to use omics techniques to understand the exact nanotoxicological effects of MWCNTs. However, the differential effects of unmodified and carboxylated MWCNTs on lipid profiles might not be related with the induction of ER stress.
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http://dx.doi.org/10.1177/10915818211056633DOI Listing
December 2021

High-Performance Work System, Strategic Flexibility, and Organizational Performance-The Moderating Role of Social Networks.

Front Psychol 2021 15;12:670132. Epub 2021 Nov 15.

Middlebury College, Middlebury, VT, United States.

Based on the dynamic capability theory, this research investigated the effect of a high-performance work system on organizational performance, the mediating role of strategic flexibility, and the moderating role of an enterprise's social network in this relationship. A total of 214 middle and senior managers from 58 Chinese enterprises were invited to participate in this research. The results showed that the high-performance work system is positively correlated with organizational performance and such correlation is partially mediated by strategic flexibility. Results found that the social network of an enterprise negatively moderated the relationship between a high-performance work system and strategic flexibility. However, the social network did not moderate the mediating role of strategic flexibility in high-performance work systems (HPWS) and organizational performance.
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http://dx.doi.org/10.3389/fpsyg.2021.670132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634683PMC
November 2021

Regulating the Homogeneity of Thiol-Maleimide Michael-Type Addition-Based Hydrogels Using Amino Biomolecules.

Gels 2021 Nov 11;7(4). Epub 2021 Nov 11.

Department of Physics, Key Laboratory of Intelligent Optical Sensing and Manipulation, National Laboratory of Solid State Microstructure, Collaborative Innovation Center of Advanced Microstructures, Ministry of Education, Nanjing University, Nanjing 210093, China.

Poly(ethylene glycol) (PEG)-based synthetic hydrogels based on Michael-type addition reaction have been widely used for cell culture and tissue engineering. However, recent studies showed that these types of hydrogels were not homogenous as expected since micro domains generated due to the fast reaction kinetics. Here, we demonstrated a new kind of method to prepare homogenous poly(ethylene glycol) hydrogels based on Michael-type addition using the side chain amine-contained short peptides. By introducing such a kind of short peptides, the homogeneity of crosslinking and mechanical property of the hydrogels has been also significantly enhanced. The compressive mechanical and recovery properties of the homogeneous hydrogels prepared in the presence of side chain amine-contained short peptides were more reliable than those of inhomogeneous hydrogels while the excellent biocompatibility remained unchanged. Furthermore, the reaction rate and gelation kinetics of maleimide- and thiol-terminated PEG were proved to be significantly slowed down in the presence of the side chain amine-contained short peptides, thus leading to the improved homogeneity of the hydrogels. We anticipate that this new method can be widely applied to hydrogel preparation and modification based on Michael-type addition gelation.
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http://dx.doi.org/10.3390/gels7040206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628763PMC
November 2021

Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals.

BMC Biol 2021 11 24;19(1):252. Epub 2021 Nov 24.

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.

Background: Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge.

Results: To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young's modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown.

Conclusion: Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.
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http://dx.doi.org/10.1186/s12915-021-01187-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611887PMC
November 2021

Effects of epigallocatechin gallate on the stability, dissolution and toxicology of ZnO nanoparticles.

Food Chem 2022 Mar 11;371:131383. Epub 2021 Oct 11.

Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, China. Electronic address:

Previously we reported the cytoprotective effects of polyphenols rich in hydroxyl groups against ZnO nanoparticles (NPs). This study used RNA-sequencing to evaluate the toxicity of ZnO NPs and epigallocatechin gallate (EGCG) to 3D Caco-2 spheroids. EGCG altered the colloidal stability of ZnO NPs, shown as the changes of atomic force microscopic height, solubility in cell culture medium, and hydrodynamic sizes. EGCG almost completely reversed ZnO NP-induced cytotoxicity, and consistently, alleviated ZnO NP-induced gene ontology (GO) terms and genes related with apoptosis. EGCG also modestly decreased intracellular Zn ions and changed GO terms and genes related with endocytosis/exocytosis in ZnO NP-exposed spheroids. Meanwhile, EGCG changed ZnO NP-induced alteration of GO terms and genes related with the functions of mitochondria, endoplasmic reticulum and lysosomes. We concluded that EGCG alleviated the cytotoxicity of ZnO NPs to 3D Caco-2 spheroids by altering NPs' colloidal properties and the pathways related with internalization and organelle dysfunction.
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http://dx.doi.org/10.1016/j.foodchem.2021.131383DOI Listing
March 2022

Target site mutations and cytochrome P450s-involved metabolism confer resistance to nicosulfuron in green foxtail (Setaria viridis).

Pestic Biochem Physiol 2021 Nov 24;179:104956. Epub 2021 Aug 24.

Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

Green foxtail [Setaria viridis (L.) P.Beauv.] is a troublesome grass weed that is widely distributed in maize (Zea mays L.) fields across China. Many populations of S. viridis have evolved resistance to the acetolactate synthase (ALS)-inhibiting herbicide nicosulfuron. The objectives of this research were to confirm nicosulfuron resistance in these populations and to investigate the basis of nicosulfuron resistance. Whole-plant dose-response experiments showed 6 out of 13 S. viridis populations were highly resistance (20-30 times) to nicosulfuron. Sequencing of the ALS gene revealed two amino acid mutations, Asp-376-Glu and Pro-197-Ala, in the nicosulfuron-resistant populations. A malathion pretreatment study revealed that the R376 and R197 subpopulations might have cytochrome P450s-mediated herbicide metabolic resistance. The resistant populations were cross-resistant to imazethapyr but sensitive to topramezone and quizalofop-p-ethyl. This is the first report of resistance to ALS inhibitors conferred by target site mutations (Asp-376-Glu or Pro-197-Ser) and possible cytochrome P450s-involved metabolism in S. viridis.
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http://dx.doi.org/10.1016/j.pestbp.2021.104956DOI Listing
November 2021

TiO nanosheets promote the transformation of vascular smooth muscle cells into foam cells in vitro and in vivo through the up-regulation of nuclear factor kappa B subunit 2.

J Hazard Mater 2022 02 7;424(Pt D):127704. Epub 2021 Nov 7.

Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China; Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, China. Electronic address:

Titanium dioxide (TiO) nanomaterials have been shown to promote atherosclerosis through endothelial dysfunction. This study investigated the toxicity of TiO nanosheets (NSs) to vascular smooth muscle cells (VSMCs), one of the pivotal cells involved in all stages of atherosclerosis. Only a high concentration of TiO NSs (128 μg/mL) modestly induced cytotoxicity by decreasing thiols. RNA-sequencing data revealed that 64 μg/mL TiO NSs significantly down-regulated 94 genes and up-regulated 174 genes, respectively. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to SMC function and lipid metabolism were altered. TiO NSs increased nuclear factor kappa B subunit 2 (NFKB2), which led to a decrease in VSMC marker actin alpha 2, smooth muscle (ACTA2). On the other hand, macrophage marker CD36 and fatty acid synthase (FASN) proteins were increased. Additionally, TiO NSs induced inflammatory cytokines and lipid accumulation, and these effects were curtailed by NFKB inhibitor - triptolide. Furthermore, repeated TiO NS injection (5 mg/kg BW, once a day for 5 continuous days) into ICR mice led to increased NFKB2, CD36 and FASN, with a decreased ACTA2. Our results suggested that TiO NSs promoted the transformation of VSMCs into foam cells through the up-regulation of NFKB2.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127704DOI Listing
February 2022

Injectable thioketal-containing hydrogel dressing accelerates skin wound healing with the incorporation of reactive oxygen species scavenging and growth factor release.

Biomater Sci 2021 Dec 21;10(1):100-113. Epub 2021 Dec 21.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China.

Wound healing is a complex dynamic process. During the occurrence of skin injury, the excessive reactive oxygen species (ROS) level is associated with sustained inflammatory response, which limits efficient wound repair. Although multifunctional hydrogels are considered ideal wound dressings due to their unique advantages, the development of hydrogel dressings with rapid gelling rates, shape adaptation, and antioxidant function is still a vital challenge. In this work, a ROS-responsive injectable polyethylene glycol hydrogel containing thioketal bonds (PEG-TK hydrogel) was synthesized and utilized to deliver epidermal growth factor (EGF). We adopted bio-orthogonal click chemistry for crosslinking the polymer chains to obtain the [email protected] hydrogel with fast gelation time, injectability and shape-adaptability. More interestingly, the thioketal bonds in the PEG-TK hydrogel not only scavenged excessive ROS in the wound sites but also achieved responsive and controlled EGF release to facilitate regeneration. The [email protected] hydrogel treatment offered the benefits of protecting cells from oxidative stress, accelerating wound closure, and reducing scar formation in the full-thickness skin defect model. This work provides a promising strategy for developing antioxidant hydrogel dressing for facilitating the repair of wounds.
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http://dx.doi.org/10.1039/d1bm01179kDOI Listing
December 2021

The Neuropeptide Y Receptor Ligand-Modified Cell Membrane Promotes Targeted Photodynamic Therapy of Zeolitic Imidazolate Frameworks for Breast Cancer.

J Phys Chem Lett 2021 Nov 12;12(46):11280-11287. Epub 2021 Nov 12.

Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, CAS Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.

Zeolitic imidazolate frameworks (ZIFs), widely regarded as promising materials for application in catalysis and separation, hold an increasingly significant position in drug delivery systems for their high drug loading capacity. Focused specifically on the rational design of targeting and bioresponsive nanovehicles, a neuropeptide Y receptor ligand (YL)-modified cell membrane camouflaged bioresponsive ZIF system ([email protected]@Ce6) was constructed for targeted photodynamic therapy of breast cancer. The biomimetic ZIF-based nanocarrier enhanced tumor accumulation by both neuropeptide Y receptor-targeted guidance and long-term stability. YL served as a good ligand-mediated selective targeting molecule for breast cancer, and red blood cell membrane-camouflaged nanocomposites displayed favorable biocompatibility. With the dual response of the ZIF to pH and adenosine triphosphate, the stimulus responsive photosensitizer Chlorin e6 delivery system effectively suppressed tumors . This work offers a platform for developing much safer and more efficient photodynamic therapy for the treatment of YR-overexpressed breast cancer.
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http://dx.doi.org/10.1021/acs.jpclett.1c03562DOI Listing
November 2021

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy.

Cell Biol Toxicol 2021 Nov 11. Epub 2021 Nov 11.

Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, 411105, People's Republic of China.

Although the neurotoxicity of ZnO nanoparticles (NPs) has been evaluated in animal and nerve cell culture models, these models cannot accurately mimic human brains. Three-dimensional (3D) brain organoids based on human-induced pluripotent stem cells have been developed to study the human brains, but this model has rarely been used to evaluate NP neurotoxicity. We used 3D brain organoids that express cortical layer proteins to investigate the mechanisms of ZnO NP-induced neurotoxicity. Cytotoxicity caused by high levels of ZnO NPs (64 μg/mL) correlated with high intracellular Zn ion levels but not superoxide levels. Exposure to a non-cytotoxic concentration of ZnO NPs (16 μg/mL) increased the autophagy-marker proteins LC3B-II/I but decreased p62 accumulation, whereas a cytotoxic concentration of ZnO NPs (64 μg/mL) decreased LC3B-II/I proteins but did not affect p62 accumulation. Fluorescence micro-optical sectioning tomography revealed that 64 μg/mL ZnO NPs led to decreases in LC3B proteins that were more obvious at the outer layers of the organoids, which were directly exposed to the ZnO NPs. In addition to reducing LC3B proteins in the outer layers, ZnO NPs increased the number of micronuclei in the outer layers but not the inner layers (where LC3B proteins were still expressed). Adding the autophagy flux inhibitor bafilomycin A1 to ZnO NPs increased cytotoxicity and intracellular Zn ion levels, but adding the autophagy inducer rapamycin only slightly decreased cellular Zn ion levels. We conclude that high concentrations of ZnO NPs are cytotoxic to 3D brain organoids via defective autophagy and intracellular accumulation of Zn ions.
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http://dx.doi.org/10.1007/s10565-021-09678-xDOI Listing
November 2021

Polypyrrole-based nanotheranostic agent for MRI guided photothermal-chemodynamic synergistic cancer therapy.

Nanoscale 2021 Nov 25;13(45):19085-19097. Epub 2021 Nov 25.

Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang Province, 315201, P. R. China.

Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO nanozyme on the surface ([email protected]) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn. Then, Mn can convert HO into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) -weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, [email protected] nanoprobes have excellent 4T1 cell-killing effect and tumor-suppressive properties. The acute toxicity assessment results indicate that [email protected] nanoprobes have good biological safety. Therefore, the as-prepared multifunctional [email protected] nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.
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http://dx.doi.org/10.1039/d1nr05508aDOI Listing
November 2021
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