Publications by authors named "Meng Yuan"

379 Publications

Selective oxidation and direct decolorization of cationic dyes by persulfate without activation.

Water Sci Technol 2021 Jun;83(11):2744-2752

School of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu 610500, Sichuan, China E-mail: Research Institute of Industrial Hazardous Waste Disposal and Resource Utilization, Southwest Petroleum University, Chengdu 610500, Sichuan, China.

The aim of this work was to investigate the selective oxidation and direct decolorization of selected organic dyes (Methylene Blue (MB), Rhodamine B (RhB) and Orange II (OrgII)) by persulfate (PDS) without activation. Results show that the decolorization rate of MB was up to 58.0% within 10 minutes, while those of RhB and OrgII were only about 29.6% and 3.0% after 80 minutes, respectively. In comparison with the negligible impacts of pH from 2.0 to 9.0 on MB and OrgII decolorization, RhB decolorization rate obviously varied with the pH changes, and acid pH condition was beneficial for RhB decolorization. Quenching tests implied that the decolorization of dyes by PDS without activation was a nonradical oxidation process rather than sulfate radical oxidation. A plausible mechanism is that the decolorization process is attributed to the charged states of the dyes at different pH conditions, and thus direct electron transfer from dyes to PDS may occur, which is responsible for the bleaching of dyes. This study points out the potential bleaching capability of PDS without activation on cationic dyes, which may have important implications for selective oxidation treatment of dye wastewater.
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http://dx.doi.org/10.2166/wst.2021.177DOI Listing
June 2021

NIR-Triggered Multi-Mode Antitumor Therapy Based on Bi Se /Au Heterostructure with Enhanced Efficacy.

Small 2021 Jun 10:e2100961. Epub 2021 Jun 10.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Of all the reaction oxygen species (ROS) therapeutic strategies, NIR light-induced photocatalytic therapy (PCT) based on semiconductor nanomaterials has attracted increasing attention. However, the photocatalysts suffer from rapid recombination of electron-hole pairs due to the narrow band gaps, which are greatly restricted in PCT application. Herein, Bi Se /Au heterostructured photocatalysts are fabricated to solve the problems by introducing Au nanoparticles (NPs) in situ on the surface of the hollow mesoporous structured Bi Se . Owing to the lower work function of Au NPs, the photo-induced electrons are easier to transfer and assemble on their surfaces, resulting in the increased separation of the electron-hole pairs with efficient ROS generation. Besides, Bi Se /Au heterostructures also enhance the photothermal efficiency due to the effective orbital overlaps with accelerated electron migrations according to density functional theory calculations. Moreover, the PLGA-PEG and the doxorubicin (DOX) are introduced for photothermal-triggered drug release in the system. The Bi Se /Au heterostructures also displays excellent infrared thermal (IRT) and computed tomography (CT) dual-modal imaging property for promising cancer diagnosis. Collectively, Bi Se /[email protected] exhibits prominent tumor inhibition effect based on synchronous PTT, PCT and chemotherapy triggered by NIR light for efficient antitumor treatment.
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http://dx.doi.org/10.1002/smll.202100961DOI Listing
June 2021

Impact of short-term exposure to extreme temperatures on diabetes mellitus morbidity and mortality? A systematic review and meta-analysis.

Environ Sci Pollut Res Int 2021 Jun 8. Epub 2021 Jun 8.

Gansu Province Hospital Rehabilitation Center, 53 Dingxi Road, Chengguan District, Lanzhou, 730000, Gansu, China.

The relationship between diabetes mellitus and short-term exposure to extreme temperatures remains controversial. A systematic review and meta-analysis were performed to assess the association between extreme temperatures and diabetes mellitus morbidity and mortality. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched since inception to January 1, 2019, and updated on November 17, 2020. The results were combined using random effects model and reported as relative risk (RR) with 95% confidence interval (CI). In total, 32 studies met the inclusion criteria. (1) Both heat and cold exposures have impact on diabetes. (2) For heat exposure, the subgroup analysis revealed that the effect on diabetes mortality (RR=1.139, 95% CI: 1.089-1.192) was higher than morbidity (RR=1.012, 95% CI: 1.004-1.019). (3) With the increase of definition threshold, the impact of heat exposure on diabetes rose. (4) A stronger association between heat exposure and diabetes was observed in the elderly (≥ 60 years old) (RR=1.040, 95% CI: 1.017-1.064). In conclusion, short-term exposure to both heat and cold temperatures has impact on diabetes. The elderly is the vulnerable population of diabetes exposure to heat temperature. Developing definitions of heatwaves at the regional level are suggested.
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http://dx.doi.org/10.1007/s11356-021-14568-0DOI Listing
June 2021

Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Life Sci 2021 Jun 5:119692. Epub 2021 Jun 5.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address:

Aims: This study investigated the renal protective effects and mechanisms of angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Materials And Methods: Mice were divided into abdominal aortic ligation alone, or treatment with LCZ696 or valsartan, whilst those undergoing sham surgery served as controls. Rat proximal renal tubular epithelial cells from the NRK-52E line were treated with control solution, LCZ696 or valsartan, in the presence or absence of Ang II for 24 h.

Key Findings: Compared to controls, abdominal aortic ligation significantly increased plasma NT-proBNP and urine neutrophil gelatinase-associated lipocalin (NGAL), which were associated with reduced renal length and velocity time integral on ultrasonography. Histology revealed wrinkling of the glomerular capillary wall and sclerosis of the glomerulus, dilatation of the Bowman's capsule, accompanied by diffuse renal tubular atrophy and fibrosis, accompanied by lower kidney index and higher percentage area of fibrosis. Increases in NGAL and decreased ANP protein and mRNA expression levels were observed. These abnormalities were significantly prevented by LCZ696 and to a lesser extent by valsartan. Cellular experiments demonstrated a central role of Ang II/transforming growth factor-β1/Smad2/3/connective tissue growth factor-dependent signaling leading to type IV collagen deposition. This upregulation was reversed by LCZ696 in a greater extent than valsartan treatment alone, accompanied by a significant improvement in NGAL.

Significance: LCZ696 can reduce kidney injury to a level beyond valsartan therapy alone in mice with cardiorenal syndrome, which can be speculated by effects on epithelial-mesenchymal transition and fibrosis through downregulating the TGF-β1/Smad2/3/CTGF/Collagen IV pathway.
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http://dx.doi.org/10.1016/j.lfs.2021.119692DOI Listing
June 2021

Effects of urban functional fragmentation on nitrogen dioxide (NO) variation with anthropogenic-emission restriction in China.

Sci Rep 2021 06 7;11(1):11908. Epub 2021 Jun 7.

Department of Land Surveying and Geo-Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Urban functional fragmentation plays an important role in assessing Nitrogen Dioxide (NO) emissions and variations. While the mediated impact of anthropogenic-emission restriction has not been comprehensively discussed, the lockdown response to the novel coronavirus disease 2019 (COVID-19) provides an unprecedented opportunity to meet this goal. This study proposes a new idea to explore the effects of urban functional fragmentation on NO variation with anthropogenic-emission restriction in China. First, NO variations are quantified by an Autoregressive Integrated Moving Average with external variables-Dynamic Time Warping (SARIMAX-DTW)-based model. Then, urban functional fragmentation indices including industrial/public Edge Density (ED) and Landscape Shape Index (LSI), urban functional Aggregation Index (AI) and Number of Patches (NP) are developed. Finally, the mediated impacts of anthropogenic-emission restriction are assessed by evaluating the fragmentation-NO variation association before and during the lockdown during COVID-19. The findings reveal negative effects of industrial ED, public LSI, urban functional AI and NP and positive effects of public ED and industrial LSI on NO variation based on the restricted anthropogenic emissions. By comparing the association analysis before and during lockdown, the mediated impact of anthropogenic-emission restriction is revealed to partially increase the effect of industrial ED, industrial LSI, public LSI, urban functional AI and NP and decrease the effect of public ED on NO variation. This study provides scientific findings for redesigning the urban environment in related to the urban functional configuration to mitigating the air pollution, ultimately developing sustainable societies.
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http://dx.doi.org/10.1038/s41598-021-91236-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184851PMC
June 2021

Homologous and heterologous serological response to the N-terminal domain of SARS-CoV-2 in humans and mice.

Eur J Immunol 2021 Jun 5. Epub 2021 Jun 5.

HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.

The increasing numbers of infected cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious threats to public health and the global economy. Most SARS-CoV-2 neutralizing antibodies target the receptor binding domain (RBD) and some the N-terminal domain (NTD) of the spike protein, which is the major antigen of SARS-CoV-2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID-19 patients, we showed that SARS-CoV-2 NTD-specific antibodies could be induced during infection. As compared to the results of SARS-CoV-2 RBD, the serological response of SARS-CoV-2 NTD is less cross-reactive with SARS-CoV, a pandemic strain which was identified in 2003. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers a supplementary strategy for serology testing, it may not be suitable as an immunogen for vaccine development. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/eji.202149234DOI Listing
June 2021

A new species of (Plecoptera, Nemouridae) and supplementary description of from the Nanling Mountains of southern China.

Zookeys 2021 20;1039:109-122. Epub 2021 May 20.

School of Horticulture and Plant Protection & Institute of Applied Entomology, Yangzhou University, Yangzhou 225009, China Yangzhou University Yangzhou China.

Two species of Nemouridae are described and illustrated from the Nanling Mountains of southern China, including a new species, from Guangxi Zhuang Autonomous Region, and a new regional record species, Li & Yang, 2006 from Hunan Province. The morphological characteristics of the new species are compared to related taxa and the new images with supplementary description of are also provided.
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http://dx.doi.org/10.3897/zookeys.1039.60144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159917PMC
May 2021

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients.

Stem Cell Res Ther 2021 May 29;12(1):313. Epub 2021 May 29.

Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.

Background: Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs-including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown.

Method: The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR.

Results: ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1-miR-145-5p-WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells.

Conclusion: Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs.
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http://dx.doi.org/10.1186/s13287-021-02388-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164820PMC
May 2021

Immunization with Aβ3-10-KLH vaccine improves cognitive function and ameliorates mitochondrial dysfunction and reduces Alzheimer's disease-like pathology in Tg-APPswe/PSEN1dE9 mice.

Brain Res Bull 2021 May 24;174:31-40. Epub 2021 May 24.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China. Electronic address:

Alzheimer's disease is a common cause of dementia, for which no disease-modifying therapy is yet available. Aβ3-10-KLH, a vaccine for active immunization, has been shown to prevent pathological changes in young transgenic models of AD, but the effects of treatment with it and its effects on mitochondrial dysfunction remain unclear. We immunized 6-month-old Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH to analyze whether it is capable of eliminating amyloid-β after its appearance. The vaccine effectively decreased amyloid-β deposits, improved cognitive function and ameliorated mitochondrial dysfunction. These results indicate the potential of Aβ3-10-KLH as a vaccine to treat AD.
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http://dx.doi.org/10.1016/j.brainresbull.2021.05.019DOI Listing
May 2021

Asymmetric catalytic alkynylation of thiazolones and azlactones for synthesis of quaternary α-amino acid precursors.

Org Biomol Chem 2021 May 25. Epub 2021 May 25.

Center for Supramolecular Chemistry and Catalysis and Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Lu, Shanghai 200444, People's Republic of China.

Asymmetric alkynylation of thiazolones and azlactones with alkynylbenziodoxolones as the electrophilic alkyne source catalyzed by thiourea phosphonium salt is described. By using thiazolones as nucleophiles, the desired alkyne functionalized thiazolones were obtained in 55-89% yields with 31-86% ee. Azlactones gave the desired products in comparable yields with lower enantioselectivities. Ring-opening of the alkynylation products led to α,α-disubstituted α-amino acid derivatives efficiently without loss of enantioselectivity.
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http://dx.doi.org/10.1039/d1ob00582kDOI Listing
May 2021

Identifying the Biomarkers and Pathways Associated with Hepatocellular Carcinoma Based on an Integrated Analysis Approach.

Liver Int 2021 May 25. Epub 2021 May 25.

1School of Biomedical Engineering, Tianjin Medical University, Tianjin, 300070, China.

Background & Aims: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. The molecular mechanism underlying HCC is still unclear. In this study, we conducted a comprehensive analysis to explore the genes, pathways and their interactions involved in HCC.

Methods: We analyzed the gene expression datasets corresponding to 488 samples from 10 studies on HCC, and identified the genes differentially expressed in HCC samples. Then, the genes were compared against Phenolyzer and GeneCards to screen those potentially associated with HCC. The features of the selected genes were explored by mapping them onto the human protein-protein interaction network, and a subnetwork related to HCC was constructed. Hub genes in this HCC specific subnetwork were identified and their relevance with HCC was investigated by survival analysis.

Results: We identified 444 differentially expressed genes (177 up-regulated and 267 down-regulated) related to HCC. Functional enrichment analysis revealed that pathways like p53 signaling and chemical carcinogenesis were eriched in HCC genes. In the subnetwork related to HCC, five disease modules were detected. Further analysis identified 6 hub genes from the HCC specific subnetwork. Survival analysis showed that the expression levels of these genes were negatively correlated with survival rate of HCC patients.

Conclusions: Based on a systems biology framework, we identified the genes, pathways, as well as the disease specific network related to HCC. We also found novel biomarkers whose expression patterns were correlated with progression of HCC, and they could be candidates for further investigation.
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http://dx.doi.org/10.1111/liv.14972DOI Listing
May 2021

NMR Based SARS-CoV-2 Antibody Screening.

J Am Chem Soc 2021 06 21;143(21):7930-7934. Epub 2021 May 21.

Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, United States.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells is a complex process that involves (1) recognition of the host entry receptor, angiotensin-converting enzyme 2 (ACE2), by the SARS-CoV-2 spike protein receptor binding domain (RBD), and (2) the subsequent fusion of the viral and cell membranes. Our long-term immune-defense is the production of antibodies (Abs) that recognize the SARS-CoV-2 RBD and successfully block viral infection. Thus, to understand immunity against SARS-CoV-2, a comprehensive molecular understanding of how human SARS-CoV-2 Abs recognize the RBD is needed. Here, we report the sequence-specific backbone assignment of the SARS-CoV-2 RBD and, furthermore, demonstrate that biomolecular NMR spectroscopy chemical shift perturbation (CSP) mapping successfully and rapidly identifies the molecular epitopes of RBD-specific mAbs. By incorporating NMR-based CSP mapping with other molecular techniques to define RBD-mAb interactions and then correlating these data with neutralization efficacy, structure-based approaches for developing improved vaccines and COVID-19 mAb-based therapies will be greatly accelerated.
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http://dx.doi.org/10.1021/jacs.1c03945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171107PMC
June 2021

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.

Science 2021 May 20. Epub 2021 May 20.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Neutralizing antibodies (nAbs) elicited against the receptor-binding site (RBS) of the spike protein of wild-type SARS-CoV-2 are generally less effective against recent variants of concern. RBS residues E484, K417 and N501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on ACE2 binding and K417N and E484K mutations on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternate binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.
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http://dx.doi.org/10.1126/science.abh1139DOI Listing
May 2021

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes.

Chin J Traumatol 2021 Apr 26. Epub 2021 Apr 26.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China. Electronic address:

Purpose: Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type.

Methods: A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor.

Results: A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores.

Conclusion: Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.
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http://dx.doi.org/10.1016/j.cjtee.2021.04.008DOI Listing
April 2021

Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19.

Cell Rep 2021 05 9;35(8):109173. Epub 2021 May 9.

HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Individuals with the 2019 coronavirus disease (COVID-19) show varying severity of the disease, ranging from asymptomatic to requiring intensive care. Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, we still lack an understanding of the overall landscape of B cell receptor (BCR) repertoires in individuals with COVID-19. We use high-throughput sequencing of bulk and plasma B cells collected at multiple time points during infection to characterize signatures of the B cell response to SARS-CoV-2 in 19 individuals. Using principled statistical approaches, we associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among individuals as candidates for responses specific to SARS-CoV-2. Using single-cell sequencing, we verify the reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identify the natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in some individuals. Our results provide insights important for development of rational therapies and vaccines against COVID-19.
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http://dx.doi.org/10.1016/j.celrep.2021.109173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106887PMC
May 2021

Critical Role of Lkb1 in the Maintenance of Alveolar Macrophage Self-Renewal and Immune Homeostasis.

Front Immunol 2021 22;12:629281. Epub 2021 Apr 22.

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

Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c cells led to greatly reduced AM abundance in the lung due to the impaired self-renewal of AMs but not the impeded pre-AM differentiation. Mice with Lkb1-deficient AMs exhibited deteriorated diseases during airway (. ) infection and allergic inflammation, with excessive accumulation of neutrophils and more severe lung pathology. Drug-mediated AM depletion experiments in wild type mice indicated a cause for AM reduction in aggravated diseases in Lkb1 conditional knockout mice. Transcriptomic sequencing also revealed that Lkb1 inhibited proinflammatory pathways, including IL-17 signaling and neutrophil migration, which might also contribute to the protective function of Lkb1 in AMs. We thus identified Lkb1 as a pivotal regulator that maintains the self-renewal and immune function of AMs.
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http://dx.doi.org/10.3389/fimmu.2021.629281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100336PMC
April 2021

Oyster biomineralization under ocean acidification: From genes to shell.

Glob Chang Biol 2021 May 8. Epub 2021 May 8.

The Swire Institute of Marine Science and School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR.

Biomineralization is one of the key processes that is notably affected in marine calcifiers such as oysters under ocean acidification (OA). Understanding molecular changes in the biomineralization process under OA and its heritability, therefore, is key to developing conservation strategies for protecting ecologically and economically important oyster species. To do this, in this study, we have explicitly chosen the tissue involved in biomineralization (mantle) of an estuarine commercial oyster species, Crassostrea hongkongensis. The primary aim of this study is to understand the influence of DNA methylation over gene expression of mantle tissue under decreased ~pH 7.4, a proxy of OA, and to extrapolate if these molecular changes can be observed in the product of biomineralization-the shell. We grew early juvenile C. hongkongensis, under decreased ~pH 7.4 and control ~pH 8.0 over 4.5 months and studied OA-induced DNA methylation and gene expression patterns along with shell properties such as microstructure, crystal orientation and hardness. The population of oysters used in this study was found to be moderately resilient to OA at the end of the experiment. The expression of key biomineralization-related genes such as carbonic anhydrase and alkaline phosphatase remained unaffected; thus, the mechanical properties of the shell (shell growth rate, hardness and crystal orientation) were also maintained without any significant difference between control and OA conditions with signs of severe dissolution. In addition, this study makes three major conclusions: (1) higher expression of Ca binding/signalling-related genes in the mantle plays a key role in maintaining biomineralization under OA; (2) DNA methylation changes occur in response to OA; however, these methylation changes do not directly control gene expression; and (3) OA would be more of a 'dissolution problem' rather than a 'biomineralization problem' for resilient species that maintain calcification rate with normal shell growth and mechanical properties.
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http://dx.doi.org/10.1111/gcb.15675DOI Listing
May 2021

The miR164-GhCUC2-GhBRC1 module regulates plant architecture through abscisic acid in cotton.

Plant Biotechnol J 2021 May 7. Epub 2021 May 7.

State Key Laboratory of Cotton Biology, Institute of Cotton Research of Chinese Academy of Agricultural Sciences, Anyang, China.

Branching determines cotton architecture and production, but the underlying regulatory mechanisms remain unclear. Here, we report that the miR164-GhCUC2 (CUP-SHAPED COTYLEDON2) module regulates lateral shoot development in cotton and Arabidopsis. We generated OE-GhCUC2m (overexpression GhCUC2m) and STTM164 (short tandem target mimic RNA of miR164) lines in cotton and heterologous expression lines for gh-miR164, GhCUC2 and GhCUC2m in Arabidopsis to study the mechanisms controlling lateral branching. GhCUC2m overexpression resulted in a short-branch phenotype similar to STTM164. In addition, heterologous expression of GhCUC2m led to decreased number and length of branches compared with wild type, opposite to the effects of the OE-gh-pre164 line in Arabidopsis. GhCUC2 interacted with GhBRC1 and exhibited similar negative regulation of branching. Overexpression of GhBRC1 in the brc1-2 mutant partially rescued the mutant phenotype and decreased branch number. GhBRC1 directly bound to the NCED1 promoter and activated its transcription, leading to local abscisic acid (ABA) accumulation and response. Mutation of the NCED1 promoter disrupted activation by GhBRC1. This finding demonstrates a direct relationship between BRC1 and ABA signalling and places ABA downstream of BRC1 in the control of branching development. The miR164-GhCUC2-GhBRC1-GhNCED1 module provides a clear regulatory axis for ABA signalling to control plant architecture.
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http://dx.doi.org/10.1111/pbi.13599DOI Listing
May 2021

The SLIM1 transcription factor is required for arsenic resistance in Arabidopsis thaliana.

FEBS Lett 2021 May 7. Epub 2021 May 7.

Division of Biological Sciences, Cell and Developmental Biology Section, University of California, La Jolla, CA, USA.

The transcriptional regulators of arsenic-induced gene expression remain largely unknown. Sulfur assimilation is tightly linked with arsenic detoxification. Here, we report that mutant alleles in the SLIM1 transcription factor are substantially more sensitive to arsenic than cadmium. Arsenic treatment caused high levels of oxidative stress in the slim1 mutants, and slim1 alleles were impaired in both thiol accumulation and sulfate accumulation. We further found enhanced arsenic accumulation in roots of slim1 mutants. Transcriptome analyses indicate an important role for SLIM1 in arsenic-induced tolerance mechanisms. The present study identifies the SLIM1 transcription factor as an essential component in arsenic tolerance and arsenic-induced gene expression. Our results suggest that the severe arsenic sensitivity of the slim1 mutants is caused by altered redox status.
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http://dx.doi.org/10.1002/1873-3468.14096DOI Listing
May 2021

A sample selection method specific to unknown test samples for calibration and validation sets based on spectra similarity.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 24;258:119870. Epub 2021 Apr 24.

School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:

As is known to all, the construction of calibration and validation sets is of great importance for how to select representative samples into subsets so that the calibration model can be built, evaluated and predicted effectively for model development. In this study, a method was proposed for the calibration and validation sets constructed by selecting samples maximally similar to the test samples based on the spectra data. Both the Euclidean distance and Mahalanobis distance were attempted to estimate the spectra similarity. The method to select samples for calibration is more suitable and specific to unknown test samples in practical applications, thus improving the measurement accuracy. In addition, the optimization of calibration set size was carried out to avoid the influence of unnecessary samples. Two data sets of Salvia miltiorrhiza (S. miltiorrhiza) and corn by near infrared spectroscopy (NIR) were used to test the performance of the proposed method compared with two typical sample-selection algorithms, Kennard-Stone (KS) and sample set partitioning based on joint x-y distances (SPXY). The experimental results indicated that the proposed method could select a more targeted set of samples for the unknown test samples and had the superior predictive performance to the KS and SPXY methods.
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http://dx.doi.org/10.1016/j.saa.2021.119870DOI Listing
September 2021

RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.

Cancer Sci 2021 May 4. Epub 2021 May 4.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

BCR-ABL1 gene fusion associated with additional DNA lesions involves the pathogenesis of chronic myelogenous leukemia (CML) from a chronic phase (CP) to a blast crisis of B lymphoid (CML-LBC) lineage and BCR-ABL1 acute lymphoblastic leukemia (BCR-ABL1 ALL). The recombination-activating gene RAG1 and RAG2 (collectively, RAG) proteins that assemble a diverse set of antigen receptor genes during lymphocyte development are abnormally expressed in CML-LBC and BCR-ABL1 ALL. However, the direct involvement of dysregulated RAG in disease progression remains unclear. Here, we generate human wild-type (WT) RAG and catalytically inactive RAG-expressing BCR-ABL1 and BCR-ABL1 cell lines, respectively, and demonstrate that BCR-ABL1 specifically collaborates with RAG recombinase to promote cell survival in vitro and in xenograft mice models. WT RAG-expressing BCR-ABL1 cell lines and primary CD34 bone marrow cells from CML-LBC samples maintain more double-strand breaks (DSB) compared to catalytically inactive RAG-expressing BCR-ABL1 cell lines and RAG-deficient CML-CP samples, which are measured by γ-H2AX. WT RAG-expressing BCR-ABL1 cells are biased to repair RAG-mediated DSB by the alternative non-homologous end joining pathway (a-NHEJ), which could contribute genomic instability through increasing the expression of a-NHEJ-related MRE11 and RAD50 proteins. As a result, RAG-expressing BCR-ABL1 cells decrease sensitivity to tyrosine kinase inhibitors (TKI) by activating BCR-ABL1 signaling but independent of the levels of BCR-ABL1 expression and mutations in the BCR-ABL1 tyrosine kinase domain. These findings identify a surprising and novel role of RAG in the functional specialization of disease progression in BCR-ABL1 leukemia through its endonuclease activity.
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http://dx.doi.org/10.1111/cas.14939DOI Listing
May 2021

Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2.

Cell Rep 2021 05 24;35(6):109109. Epub 2021 Apr 24.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.
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http://dx.doi.org/10.1016/j.celrep.2021.109109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064889PMC
May 2021

Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: An in vivo study.

Photodiagnosis Photodyn Ther 2021 Apr 27;34:102311. Epub 2021 Apr 27.

Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China. Electronic address:

Background And Aim: Antimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections.

Methods: The cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer.

Results: AE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald.

Conclusions: AE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102311DOI Listing
April 2021

Graphene-Based Environmental Sensors: Electrical and Optical Devices.

Molecules 2021 Apr 9;26(8). Epub 2021 Apr 9.

Department of Chemistry, Boston University, Boston, MA 02215, USA.

In this review paper, we summarized the recent progress of using graphene as a sensing platform for environmental applications. Especially, we highlight the electrical and optical sensing devices developed based on graphene and its derivatives. We discussed the role of graphene in these devices, the sensing mechanisms, and the advantages and disadvantages of specific devices. The approaches to improve the sensitivity and selectivity are also discussed.
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http://dx.doi.org/10.3390/molecules26082165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070241PMC
April 2021

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.

Cell Host Microbe 2021 05 15;29(5):806-818.e6. Epub 2021 Apr 15.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.
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http://dx.doi.org/10.1016/j.chom.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049401PMC
May 2021

Insights into Persistent Toxic Substances in Protective Cases of Mobile Phones: Occurrence, Health Risks, and Implications.

Environ Sci Technol 2021 05 15;55(9):6076-6086. Epub 2021 Apr 15.

State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China.

Despite the popularity of smartphones worldwide, persistent toxic substances (PTSs) in protective cases of mobile phones (PCMPs) and their health risks via direct skin contact have been ignored. This study investigated PTSs in PCMPs made in China with different materials and sales territory and their potential harm to human health. Polybrominated diphenyl ethers (PBDEs, 6.40 ng/g), new brominated flame retardants (NBFRs, 144 ng/g), organophosphate esters (OPEs, 10.1 μg/g), short-chain chlorinated paraffins (SCCPs, 3.58 μg/g), medium-chain chlorinated paraffins (MCCPs, 3.17 μg/g), and heavy metals (HMs, 72.3 μg/g) were detected. It was found that the different concentrations and compositions depend on the material, region, and use. Moreover, the raw materials used to fabricate PCMPs are of variable quality and may include recycled plastic waste. There are no standard quality specifications for PCMPs, and different materials have different properties, including specific surface area and adsorption ability. The risk assessment performed by Monte Carlo simulations indicated that the PTSs evaluated pose no health risks to the general population and may have adverse effects on individual high-exposure populations. According to the results of this work, it is suggested that more stringent global specifications for the selection of raw materials should be established, including the content and structural characteristics of PTSs, limitations on the use of additives in the production process, and the handling after use.
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http://dx.doi.org/10.1021/acs.est.0c07603DOI Listing
May 2021

In Vivo X-ray Triggered Catalysis of H Generation for Cancer Synergistic Gas Radiotherapy.

Angew Chem Int Ed Engl 2021 Jun 5;60(23):12868-12875. Epub 2021 May 5.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, 350108, P. R. China.

To date, hydrogen (H ) therapy has received widespread attention. However, X-ray triggered sustainable H -producing materials with controlled release for cancer treatment have not been reported. Herein, an X-ray triggered sustainable in situ H producing platform, Au NR-TiO @ZnS:Cu,Co-A(Au-TiO @ZnS), composed of Au-amorphous TiO nano-dumbbell-shaped heterostructure coated with long afterglow particles, was developed for cancer synergistic H -radiotherapy. The mechanism of H production was verified by theoretical calculations and in vitro experiments. Changes in the apoptosis pathway caused by the synergistic effect of H and radiotherapy were reported. Guided by its excellent photoacoustic imaging capabilities, mice with orthotopic liver cancer achieved excellent therapeutic effects and low inflammatory side effects, suggesting that Au-TiO @ZnS has promising application potential for cancer treatment and prognosis.
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http://dx.doi.org/10.1002/anie.202100002DOI Listing
June 2021

A protective broadly cross-reactive human antibody defines a conserved site of vulnerability on beta-coronavirus spikes.

bioRxiv 2021 Mar 31. Epub 2021 Mar 31.

We recently described CC40.8 bnAb from a COVID-19 donor that exhibits broad reactivity with human β-CoVs. Here, we show that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 Å resolution and found that the peptide adopts a mainly helical structure. Conserved residues in β-CoVs interact with the antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibits protective efficacy against SARS-CoV-2 challenge in a hamster model with reduction in weight loss and lung viral titers. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational vaccine strategies. Overall, our study describes a new target on CoV spikes for protective antibodies that may facilitate the development of pan-β-CoV vaccines.

Summary: A human mAb isolated from a COVID-19 donor defines a protective cross-neutralizing epitope promising for pan-β-CoV vaccine strategies.
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http://dx.doi.org/10.1101/2021.03.30.437769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020973PMC
March 2021

Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants.

bioRxiv 2021 Apr 1. Epub 2021 Apr 1.

The emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonals and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1101/2021.04.01.437942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020967PMC
April 2021

Conferring Ti-Based MOFs with Defects for Enhanced Sonodynamic Cancer Therapy.

Adv Mater 2021 May 1;33(18):e2100333. Epub 2021 Apr 1.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

The development of highly efficient, multifunctional, and biocompatible sonosensitizer is still a priority for current sonodynamic therapy (SDT). Herein, a defect-rich Ti-based metal-organic framework (MOF) (D-MOF(Ti)) with greatly improved sonosensitizing effect is simply constructed and used for enhanced SDT. Compared with the commonly used sonosensitizer TiO , D-MOF(Ti) results in a superior reactive oxygen species (ROS) yield under ultrasound (US) irradiation due to its narrow bandgap, which principally improves the US-triggered electron-hole separation. Meanwhile, due to the existence of Ti ions, D-MOF(Ti) also exhibits a high level of Fenton-like activity to enable chemodynamic therapy. Particularly, US as the excitation source of SDT can simultaneously enhance the Fenton-like reaction to achieve remarkably synergistic outcomes for oncotherapy. More importantly, D-MOF(Ti) can be degraded and metabolized out of the body after completion of its therapeutic functions without off-target toxicity. Overall, this work identifies a novel Ti-familial sonosensitizer harboring great potential for synergistic sonodynamic and chemodynamic cancer therapy.
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http://dx.doi.org/10.1002/adma.202100333DOI Listing
May 2021