Publications by authors named "Pengfei Wang"

719 Publications

Hydrogen-Bonding Controlled Nickel-Catalyzed Regioselective Cyclotrimerization of Terminal Alkynes.

Org Lett 2021 May 10. Epub 2021 May 10.

Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China.

Herein we report a hydrogen-bonding controlled nickel-catalyzed regioselective cyclotrimerization of terminal alkynes in moderate to excellent yields with high regioselectivities toward 1,3,5-trisubstituted benzenes. This method features a cheap catalyst, mild reaction conditions, and excellent functional group compatibility. The Ni-B(OH) complex generated from NiCl·DME and tetrahydroxydiboron might act as an active catalyst. After three consecutive -additions of terminal alkynes, internal migratory insertion cyclization, and β-boron elimination induced aromatization, 1,3,5-trisubstituted benzenes were selectively established.
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http://dx.doi.org/10.1021/acs.orglett.1c01095DOI Listing
May 2021

Effects of miR-204 on apoptosis and inflammatory response of Clostridium perfringens beta2 toxin induced IPEC-J2 cells via targeting BCL2L2.

Microb Pathog 2021 May 6:104906. Epub 2021 May 6.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Research Center for Swine Production Engineering and Technology, Lanzhou, 730070, China. Electronic address:

Clostridium perfringens beta2 (CPB2) toxin can cause intestinal damage and inflammatory responses in a variety of animals, which seriously endanger the healthy development of animal husbandry. Increasing evidence has demonstrated that microRNAs (miRNAs) can play an important regulatory role in the process of pathogenic infection. In our previous study, we found that miR-204 was highly expressed in the ileum tissues of the susceptible group diarrhea piglets after infection with Clostridium perfringens (C. perfringens) type C. In this study, we found that miR-204 was also up-regulated in different time points after CPB2 toxin treatment. Overexpression of miR-204 promoted apoptosis and inflammatory response of intestinal porcine epithelial cells (IPEC-J2), whereas the opposite results were displayed after transfected with miR-204 inhibitor. Furthermore, the luciferase reporter assays confirmed that BCL2L2 was a direct target gene of miR-204. Interestingly, we found that overexpression BCL2L2 attenuated the apoptosis and inflammatory response of CPB2 toxin induced IPEC-J2 cells. In conclusion, these results find that miR-204 promotes the apoptosis and intensify inflammatory response of CPB2 toxin induced IPEC-J2 cells via targeting BCL2L2. These data provide a valuable reference for the piglets resistance diarrhea at the molecular level.
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http://dx.doi.org/10.1016/j.micpath.2021.104906DOI Listing
May 2021

Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex.

Sci Rep 2021 05 7;11(1):9803. Epub 2021 May 7.

Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.
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http://dx.doi.org/10.1038/s41598-021-89379-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105332PMC
May 2021

Self-assembly of Amphiphilic Porphyrins to Construct Nanoparticles for Highly Efficient Photodynamic Therapy.

Chemistry 2021 May 7. Epub 2021 May 7.

Chinese Academy of Sciences, Techn. Inst. Phys & Chem, No.29, Zhongguancun East Road, Haidian District, 100190, Beijing, CHINA.

Hydrophobic photosensitizers greatly affect the cell permeability and enrichment in tumours. They cannot be used directly for clinical applications because they always reunite in water, preventing their circulation in the blood and accumulation in tumour cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, we propose an efficient synthesis strategy that converts small molecules into nanoparticles in 100% aqueous solution via the molecular assemble without addition of any foreign species. Three photosensitizers with triphenylphosphine units and different lengths of ethylene glycol chains are synthesized as TPP-PPh 3 , TPP-PPh 3 -2PEG and TPP-PPh 3 -4PEG to improve amphiphilicity. Among of three photosensitizers, TPP-PPh3-4PEG is the most efficient (singlet oxygen yield: 0.89) for tumour photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.
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http://dx.doi.org/10.1002/chem.202101199DOI Listing
May 2021

Parameters Indicating Development of Influenza-Associated Acute Necrotizing Encephalopathy: Experiences from a Single Center.

Med Sci Monit 2021 May 2;27:e930688. Epub 2021 May 2.

Department of Pediatric Neurology, Guangzhou Women's and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.
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http://dx.doi.org/10.12659/MSM.930688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101270PMC
May 2021

Enhanced 3.9  µm emission from diode pumped Ho/Eu codoped fluoroindate glasses.

Opt Lett 2021 May;46(9):2031-2034

The use of codoping for enhancing the :→ emission in fluoroindate glasses shows that could depopulate the lower laser state : while having little effect on the upper state :, resulting in greater population inversion. The / codoped glass has high spontaneous transition probability (6.31) together with large emission cross section (7.68×10). This study indicates that codoping of with is a feasible alternative to quench the lower energy level of the 3.9 µm emission and the / codoped fluoroindate glass is a promising material for efficient 3.9 µm fiber lasers.
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http://dx.doi.org/10.1364/OL.423399DOI Listing
May 2021

Exploring the Species Diversity of Edible Mushrooms in Yunnan, Southwestern China, by DNA Barcoding.

J Fungi (Basel) 2021 Apr 17;7(4). Epub 2021 Apr 17.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming 650032, China.

Yunnan Province, China, is famous for its abundant wild edible mushroom diversity and a rich source of the world's wild mushroom trade markets. However, much remains unknown about the diversity of edible mushrooms, including the number of wild edible mushroom species and their distributions. In this study, we collected and analyzed 3585 mushroom samples from wild mushroom markets in 35 counties across Yunnan Province from 2010 to 2019. Among these samples, we successfully obtained the DNA barcode sequences from 2198 samples. Sequence comparisons revealed that these 2198 samples likely belonged to 159 known species in 56 different genera, 31 families, 11 orders, 2 classes, and 2 phyla. Significantly, 51.13% of these samples had sequence similarities to known species at lower than 97%, likely representing new taxa. Further phylogenetic analyses on several common mushroom groups including 1536 internal transcribed spacer (ITS) sequences suggested the existence of 20 new (cryptic) species in these groups. The extensive new and cryptic species diversity in wild mushroom markets in Yunnan calls for greater attention for the conservation and utilization of these resources. Our results on both the distinct barcode sequences and the distributions of these sequences should facilitate new mushroom species discovery and forensic authentication of high-valued mushrooms and contribute to the scientific inventory for the management of wild mushroom markets.
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http://dx.doi.org/10.3390/jof7040310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074183PMC
April 2021

[Brain tissue microstructure parameters estimation method based on proximal gradient network].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Apr;38(2):333-341

Institute of Electric Engineering, Yanshan University, Qinhuangdao, Hebei 066004, P.R.China.

Diffusion tensor imaging technology can provide information on the white matter of the brain, which can be used to explore changes in brain tissue structure, but it lacks the specific description of the microstructure information of brain tissue. The neurite orientation dispersion and density imaging make up for its shortcomings. But in order to accurately estimate the brain microstructure, a large number of diffusion gradients are needed, and the calculation is complex and time-consuming through maximum likelihood fitting. Therefore, this paper proposes a kind of microstructure parameters estimation method based on the proximal gradient network, which further avoids the classic fitting paradigm. The method can accurately estimate the parameters while reducing the number of diffusion gradients, and achieve the purpose of imaging quality better than the neurite orientation dispersion and density imaging model and accelerated microstructure imaging via convex optimization model.
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http://dx.doi.org/10.7507/1001-5515.202004043DOI Listing
April 2021

Identification of Seven-Gene Hypoxia Signature for Predicting Overall Survival of Hepatocellular Carcinoma.

Front Genet 2021 9;12:637418. Epub 2021 Apr 9.

Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.

Background: Hepatocellular carcinoma (HCC) is ranked fifth among the most common cancer worldwide. Hypoxia can induce tumor growth, but the relationship with HCC prognosis remains unclear. Our study aims to construct a hypoxia-related multigene model to predict the prognosis of HCC.

Methods: RNA-seq expression data and related clinical information were download from TCGA database and ICGC database, respectively. Univariate/multivariate Cox regression analysis was used to construct prognostic models. KM curve analysis, and ROC curve were used to evaluate the prognostic models, which were further verified in the clinical traits and ICGC database. GSEA analyzed pathway enrichment in high-risk groups. Nomogram was constructed to predict the personalized treatment of patients. Finally, real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expressions of KDELR3 and SCARB1 in normal hepatocytes and 4 HCC cells. The expressions of SCARB1 in hepatocellular carcinoma tissue in 46 patients were detected by immunohistochemistry, and the correlation between its expressions and disease free survival of patient was calculated.

Results: Through a series of analyses, seven prognostic markers related to HCC survival were constructed. HCC patients were divided into the high and low risk group, and the results of KM curve showed that there was a significant difference between the two groups. Stratified analysis, found that there were significant differences in risk values of different ages, genders, stages and grades, which could be used as independent predictors. In addition, we assessed the risk value in the clinical traits analysis and found that it could accelerate the progression of cancer, while the results of GSEA enrichment analysis showed that the high-risk group patients were mainly distributed in the cell cycle and other pathways. Then, Nomogram was constructed to predict the overall survival of patients. Finally, RT-qPCR showed that KDELR3 and SCARB1 were highly expressed in HepG2 and L02, respectively. Results of IHC staining showed that SCARB1 was highly expressed in cancer tissues compared to adjacent normal liver tissues and its expression was related to hepatocellular carcinoma differentiation status. The Kaplan-Meier survival showed a poor percent survival in the SCARB1 high group compared to that in the SCARB1 low group.

Conclusion: This study provides a potential diagnostic indicator for HCC patients, and help clinicians to deepen the comprehension in HCC pathogenesis so as to make personalized medical decisions.
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http://dx.doi.org/10.3389/fgene.2021.637418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075060PMC
April 2021

Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization.

Cell Host Microbe 2021 Apr 18. Epub 2021 Apr 18.

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address:

The emergence of SARS-CoV-2 variants has raised concerns about altered sensitivity to antibody-mediated immunity. The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been recently investigated. We report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies but also more resistant to neutralization by convalescent plasma and vaccinee sera. The magnitude of resistance is greater for monoclonal antibodies than vaccinee sera and evident with both pseudovirus and authentic P.1 virus. The cryoelectron microscopy structure of a soluble prefusion-stabilized spike reveals that the P.1 trimer adopts exclusively a conformation in which one of the receptor-binding domains is in the "up" position, which is known to facilitate binding to entry receptor ACE2. The functional impact of P.1 mutations thus appears to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so protective vaccine efficacy.
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http://dx.doi.org/10.1016/j.chom.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053237PMC
April 2021

A DNA-binding, albumin-targeting fusion protein promotes the cellular uptake and bioavailability of framework DNA nanostructures.

Nanoscale 2021 Mar 19;13(12):6038-6042. Epub 2021 Mar 19.

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Framework DNA nanostructures exhibit unique characteristics such as precisely controllable physicochemical properties (i.e. size, shape, and surface functionality) and have been used as carriers for the delivery of a variety of therapeutics. Nevertheless, pristine DNA nanostructures encounter challenges such as low cellular uptake efficiency and short in vivo retention time that largely hinder their biomedical applications. Here in this report, a fusion protein is designed to complex with a tetrahedral DNA nanostructure (TDN) to circumvent these challenges by recruiting serum albumins. This bi-functional fusion protein (ABS) is composed of an albumin-binding domain (ABD) and a DNA-binding domain (Sso-7d), which can serve as a linker to bridge the TDN with albumin. It was revealed that ABS-tethered TDN can readily recruit serum albumins to achieve significantly enhanced uptake in cancer cells and longer retention time in mice, suggesting that ABS may serve as a potent agent to facilitate the biological applications of DNA nanostructures.
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http://dx.doi.org/10.1039/d0nr07967gDOI Listing
March 2021

d-Glucose Isomerization with PAMAM Dendrimers as Environmentally Friendly Catalysts.

J Agric Food Chem 2021 May 21;69(17):5105-5112. Epub 2021 Apr 21.

Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.

The isomerization of d-glucose to d-fructose plays a key role in the biochemical and chemical conversion of biomass, and it is therefore desirable to develop and improve catalysts for this reaction. In this study, the environmentally friendly polymer poly(amidoamine) (PAMAM) dendrimer's properties as catalysts for this isomerization are investigated. The experimental results showed that the PAMAM dendrimers, which have basic terminal groups, can effectively promote the d-glucose isomerization reaction. Under the optimized reaction conditions, d-fructose was generated with a 20% maximum yield and above 90% selectivity. C and H isotope experiments by NMR were carried out to explore the reaction mechanism. When the reaction was performed in DO, the C1 signal of d-fructose changed to a triplet, which confirmed that the C1 carbon binds to a deuterium atom, i.e., isotopic exchange. It was also found that the deuterium atom at the C2 position of d-glucose-2-d cannot transfer to d-fructose. These data indicate that PAMAM dendrimers catalyze d-glucose isomerization through a mechanism, which includes deprotonation, formation of ene-diol intermediate, and proton exchange with the solvent.
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http://dx.doi.org/10.1021/acs.jafc.1c01088DOI Listing
May 2021

Ultrasound-Enhanced Self-Exciting Photodynamic Therapy Based on Hypocrellin B.

Chem Asian J 2021 Apr 21. Epub 2021 Apr 21.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials and CityU-CAS Joint Laboratory of Functional Materials and Devices, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment.
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http://dx.doi.org/10.1002/asia.202100205DOI Listing
April 2021

Optimising glyphosate tolerance in rapeseed (Brassica napus L.) by CRISPR/Cas9-based geminiviral donor DNA replicon system with Csy4-based single-guide RNA processing.

J Exp Bot 2021 Apr 19. Epub 2021 Apr 19.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, China.

Rapeseed (Brassica napus L.) is an important oil crop worldwide, and effective weed control can protect its yields and quality. Farmers can benefit from tolerant cultivars when using herbicides, such as glyphosate. Amino acid substitutions in enolpyruvylshikimate-3-phosphate synthase (EPSPS) render the plant less sensitive to glyphosate. Therefore, we aimed to optimise the glyphosate tolerance trait in rapeseed via endogenous EPSPS modification. To achieve effective gene replacement in B. napus L., we employed a CRISPR/Cas9 system expressing single-guide RNAs (sgRNAs) cleaved by the CRISPR-associated RNA endoribonuclease Csy4 from Pseudomonas aeruginosa for targeted induction of double-strand breaks. Both the donor template and a geminiviral replicon harbouring an sgRNA expression cassette were introduced into plant cells. Using sgRNAs targeting adjacent donor DNA template containing synonymous mutations in sgRNA sites, we achieved precise gene replacements in the endogenous B. napus EPSPS gene, BnaC04EPSPS, resulting in TIPS and LFGAAGMCRL amino acid substitutions at frequencies up to 20%. Rapeseed seedlings harbouring EPSPSmTIPS or EPSPSmLFGAAGMCRL were glyphosate tolerant. Furthermore, modifications in BnaC04EPSPS were precisely transmitted to the next generation. Our genome editing strategy enables highly efficient gene targeting and the induction of glyphosate tolerance in oilseed rape.
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http://dx.doi.org/10.1093/jxb/erab167DOI Listing
April 2021

CDK14/β-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo.

J Gene Med 2021 Apr 19:e3343. Epub 2021 Apr 19.

Department of Post-anesthetic ICU, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Introduction: Chemotherapy and radiotherapy have been reported to be basically ineffective for pancreatic ductal adenocarcinoma (PDAC) patients; thus, gene therapy might provide a novel approach for them. CDK14, a new oncogenic member of CDK family involving in pancreatic cancer cell response to Gemcitabine (GEM) treatment, has been reported to be regulated by miRNAs. In this study, we aimed to investigate whether miR-26b regulated CDK14 expression to affect the phenotype of pancreatic cancer cells.

Methods: Overexpression or knockdown of CDK14 or miR-26b was generated in pancreatic cancer cell lines and determined the function of CDK14 and miR-26b on cell phenotype and Wnt signaling pathway using MTT, EdU, transwell assays, xenograft model and westernblot. The predicted binding site between 3'UTR of CDK14 and miR-26b, miR-26b promoter and TCF4 was verified by luciferase assays or CHIP assays.

Results: CDK14 overexpression inhibited the p-GSK3β while promoted the p-LRP6, the nuclear translocation of β-catenin, and the transactivation of the TCF4 transcription factor, thus promoting pancreatic cancer cell aggressiveness. miR-26b directly targeted CDK14 and inhibited CDK14 expression. In vitro and vivo, miR-26b overexpression inhibited, whereas CDK14 overexpression promoted cancer cell aggressiveness; CDK14 overexpression partially attenuated miR-26b overexpression effects on cancer cells. The effects of miR-26b overexpression on tumor growth and the Wnt/β-catenin/TCF4 signaling were partially reversed by CDK14 overexpression. TCF4 inhibited the expression of miR-26b via targeting its promoter region.

Conclusion: CDK14, β-catenin, TCF4, and miR-26b form a positive feedback regulation to modulate pancreatic cancer cell phenotypes in vitro and tumor growth in vivo.
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http://dx.doi.org/10.1002/jgm.3343DOI Listing
April 2021

Achieving high singlet-oxygen generation by applying the heavy-atom effect to thermally activated delayed fluorescent materials.

Chem Commun (Camb) 2021 Apr 19. Epub 2021 Apr 19.

Center of Super-Diamond and Advanced Films (COSDAF) and Department of Chemistry, City University of Hong Kong, Hong Kong, 999077, P. R. China. and Joint Laboratory of Nano-Organic Functional Materials and Devices (TIPC and CityU), City University of Hong Kong, Kowloon, Hong Kong SAR, P. R. China.

A bromine-substituted thermally activated delayed fluorescent (TADF) molecule AQCzBr2 is designed with both small singlet-triplet splitting (ΔEST) and increased spin-orbit coupling (SOC) to boost intersystem crossing (ISC) for singlet oxygen generation. AQCzBr2 nanoparticles (NPs) demonstrate high productivity of singlet oxygen generation (ΦΔ = 0.91) which allows highly efficient photodynamic therapy toward cancer cells.
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http://dx.doi.org/10.1039/d0cc08323bDOI Listing
April 2021

An Immuno-Cardiac Model for Macrophage-Mediated Inflammation in COVID-19 Hearts.

Circ Res 2021 Apr 15. Epub 2021 Apr 15.

Surgery, Cornell University Medical Center, UNITED STATES.

While respiratory failure is a frequent and clinically significant outcome of COVID-19, cardiac complications are a common feature in hospitalized COVID-19 patients and are associated with worse patient outcomes. The cause of cardiac injury in COVID-19 patients is not yet known. Case reports of COVID-19 autopsy heart samples have demonstrated abnormal inflammatory infiltration of macrophages in heart tissues. Generate an immuno-cardiac co-culture platform to model macrophage-mediated hyper-inflammation in COVID-19 hearts and screen for drugs that can block the macrophage-mediated inflammation. We systematically compared autopsy samples from non-COVID-19 donors and COVID-19 patients using RNA-seq and immunohistochemistry. We observed strikingly increased expression levels of CCL2 as well as macrophage infiltration in heart tissues of COVID-19 patients. We generated an immuno-cardiac co-culture platform containing human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) and macrophages. We found that macrophages induce increased reactive oxygen species (ROS) and apoptosis in CMs by secreting IL-6 and TNF-α after SARS-CoV-2 exposure. Using this immuno-cardiac co-culture platform, we performed a high content screen and identified ranolazine and tofacitinib as compounds that protect CMs from macrophage-induced cardiotoxicity. We established an immuno-host co-culture system to study macrophage-induced host cell damage following SARS-CoV-2 infection and identified FDA-approved drug candidates that alleviate the macrophage-mediated hyper-inflammation and cellular injury.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319060DOI Listing
April 2021

Anti-CLL1 Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed/Refractory Acute Myeloid Leukemia.

Clin Cancer Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, P.R. China.

Purpose: The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR T in AML treatment. This study aimed to test the safety and efficacy of CAR T-cell therapy in R/R-AML.

Patients And Methods: Four pediatric patients with R/R-AML were enrolled in the ongoing phase I/II anti-CLL1 CAR T-cell therapy trial. The CAR design was based on an apoptosis-inducing gene, FKBP-caspase 9, to establish a safer CAR (4SCAR) application. Anti-CLL1 CAR was transduced into peripheral blood mononuclear cells of the patients via lentivector 4SCAR, followed by infusion into the recipients after lymphodepletion chemotherapy. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other adverse events were documented. Treatment response was evaluated by morphology and flow cytometry-based minimal residual disease assays.

Results: Three patients with R/R-AML achieved complete remission and minimal residual disease negativity, while the other patient remained alive for 5 months. All these patients experienced low-grade and manageable adverse events.

Conclusions: On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4543DOI Listing
April 2021

Natural and Synthetic Saponins as Vaccine Adjuvants.

Authors:
Pengfei Wang

Vaccines (Basel) 2021 Mar 5;9(3). Epub 2021 Mar 5.

Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1/Th2 immunity, which is valuable to a broad scope of applications in combating various microbial pathogens, cancers, and other diseases. It has recently been approved for use in human vaccines as a key component of combination adjuvants, e.g., AS01b in Shingrix for herpes zoster. Despite its usefulness in research and clinic, the cellular and molecular mechanisms of QS-21 and other saponin adjuvants are poorly understood. Extensive efforts have been devoted to studies for understanding the mechanisms of QS-21 in different formulations and in different combinations with other adjuvants, and to medicinal chemistry studies for gaining mechanistic insights and development of practical alternatives to QS-21 that can circumvent its inherent drawbacks. In this review, we briefly summarize the current understandings of the mechanism underlying QS-21's adjuvanticity and the encouraging results from recent structure-activity-relationship (SAR) studies.
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http://dx.doi.org/10.3390/vaccines9030222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001307PMC
March 2021

Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.

Cell Rep 2021 04 19;35(1):108950. Epub 2021 Mar 19.

Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address:

Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determine the structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three use VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy-chain N53I-enhancing binding and light-chain tyrosines recognizing F486. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD-a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.
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http://dx.doi.org/10.1016/j.celrep.2021.108950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972811PMC
April 2021

High-sensitivity, fast-response ethanol gas optical sensor based on a dual microfiber coupler structure with the Vernier effect.

Opt Lett 2021 Apr;46(7):1558-1561

A high-sensitivity ethanol gas sensor based on two microfiber couplers and the Vernier effect is examined in this Letter using the unique variation rate conversion point characteristics. The output spectrum of the two couplers connected in parallel are superimposed to form a symmetrical envelope curve, showing high responsivity to variations in the external environment. Ethanol sensitivity was achieved by coating the waist region of the coupler with a mixture of Nile red and polymethyl methacrylate. When the concentration of ethanol gas changes, the envelope spectrum shifts. Experimental results show that a high responsivity of 160 pm/ppm can be obtained by tracing the reference peaks in the envelope curve and that the response and recovery times are on the order of seconds.
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http://dx.doi.org/10.1364/OL.418953DOI Listing
April 2021

Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.

Cell Host Microbe 2021 Mar 12. Epub 2021 Mar 12.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address:

Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite.
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http://dx.doi.org/10.1016/j.chom.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953435PMC
March 2021

Arsenic speciation and bioaccessibility in raw and cooked seafood: Influence of seafood species and gut microbiota.

Environ Pollut 2021 Mar 17;280:116958. Epub 2021 Mar 17.

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 101408, China; Research Center for Eco-environmental Sciences, Chinese Academy of Science, Beijing, 100085, China. Electronic address:

Seafood is an important source of arsenic (As) exposure for humans. In this study, 34 seafood samples (fishes, shellfishes, and seaweeds) collected from different markets in China were analysed for total and speciated As before and after boiling. Furthermore, the As bioaccessibility was also assessed using a physiologically based extraction test combined with the Simulator of Human Intestinal Microbial Ecosystems. The results showed that the total As (tAs) contents of seaweeds (raw: 44.12; boiled: 31.13, μg·g dw) were higher than those of shellfishes (raw: 8.34; boiled: 5.14, μg·g dw) and fishes (raw: 6.01; boiled: 3.25, μg·g dw). Boiling significantly decreased the As content by 22.24% for seaweeds, 32.27% for shellfishes, and 41.42% in fishes, respectively (p < 0.05). During in vitro digestion, the bioaccessibility of tAs and arsenobetaine (AsB) significantly varied between the investigated species of seafood samples in gastric (G) and small intestinal phases (I) (p < 0.05). Higher tAs bioaccessibility (G: 68.6%, I: 81.9%) were obtained in fishes than shellfishes (G: 40.9%, I: 52.5%) and seaweeds (G: 31%, I: 53.6%). However, there was no significant differences in colonic phase (C) (p > 0.05). With the effect of gut microbiota, arsenate (As) was transformed into monomethylarsonic acid (MMA) and arsenite (As) in C. Moreover, as for seaweeds, an unknown As compound was produced.
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http://dx.doi.org/10.1016/j.envpol.2021.116958DOI Listing
March 2021

Effect of gut microbiota on in vitro bioaccessibility of heavy metals and human health risk assessment from ingestion of contaminated soils.

Environ Pollut 2021 Jun 15;279:116943. Epub 2021 Mar 15.

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 101408, PR China; Research Center for Eco-Environment Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China. Electronic address:

To identify the role of gut microbiota in human health risk assessment, the bioaccessibility of heavy metals in 14 soil samples were determined in simulated gastrointestinal fluids. Compared to the small intestinal phase, the bioaccessibility values of the colon phase varied, either increased by 3.5-fold for As, by 2.2-fold for Cr, and by 1.6-fold for Ni, or reduced by 4.4-fold for Cu, respectively. The colon incubation with adult gut microbiota yielded higher bioaccessibility value of As (1.3 times) and Fe (3.4 times) than that of the child in most soil samples. Colon bioaccessibility was about 60% greater of Cd for the adult and 30% higher of Cr for the child. Congruent data on the bioaccessibility of Cu and Ni was observed. In addition, correlation analysis indicated that in vitro bioaccessibility was primarily related to total concentrations of heavy metals in soils, followed by soil pH and active Fe/Mn oxide. Significantly, risk assessment calculated based on colon bioaccessibility indicated that the target hazard quotient (THQ > 1) of As was presented in 3 soil samples for the adult (1.05-3.35) and in 9 soil samples for the child (1.06-26.93). The hazard index (HI) of the child was 4.00 on average, greater than that of the adult (0.62), primarily due to the contribution of As and Cd. It suggested non-carcinogenic risks are likely to occur in children through typical hand-to-mouth behavior. The adjustment of colon bioaccessibility will result in more accurate risk assessment of human exposure to heavy metals from oral ingestion of contaminated soils.
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http://dx.doi.org/10.1016/j.envpol.2021.116943DOI Listing
June 2021

Compact all-fiber thermo-optic modulator based on a Michelson interferometer coated with NaNdF nanoparticles.

Opt Express 2021 Mar;29(5):6854-6862

We propose and investigate an all-fiber thermo-optic modulator based on a side-polished twin-core fiber (TCF) Michelson interferometer (MI) coated with NaNdF nanoparticles. The MI was fabricated by tapering the splicing point between the TCF and a single mode fiber (SMF). A short suspended core fiber (SCF) is spliced to one core of the TCF to introduce a fixed optical phase difference (OPD). The side-polished core is coated with photo-thermal material NaNdF. Owing to the ohmic heating of NaNdF nanoparticles under 808 nm pump laser, the effective refractive index of the polished core is changed, resulting in a phase shift of the MI. The MI has a significant modulation phase shift with 2.9 π near the wavelength of 1260 nm and can obtain an optical switching with a rise (fall) time of 152 (50) ms. The proposed device will have a great application potential in optical modulators due to compact structure and strong robustness.
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http://dx.doi.org/10.1364/OE.419621DOI Listing
March 2021

Water-Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR-II Photothermal Anti-Bacterial Therapy.

Angew Chem Int Ed Engl 2021 May 16;60(21):11758-11762. Epub 2021 Apr 16.

Center of Super-Diamond and Advanced Films (COSDAF) & Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, P. R. China.

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.
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http://dx.doi.org/10.1002/anie.202101406DOI Listing
May 2021

Combination CTLA-4 immunoglobulin treatment and ultrasound microbubble-mediated exposure improve renal function in a rat model of diabetic nephropathy.

Aging (Albany NY) 2021 03 10;13(6):8524-8540. Epub 2021 Mar 10.

Department of Ultrasonic Diagnosis, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.

Objective: This study explored the therapeutic impact of combined cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA-4-Ig) treatment and microbubble-mediated exposure in a rat model of diabetic nephropathy (DN).

Method: We treated rats using CTLA-4-Ig and/or microbubble exposure. At 8 weeks post-intervention, key parameters were evaluated including blood biochemistry, damage to renal tissue, renal parenchymal elasticity, ultrastructural changes in podocytes, and renal parenchymal expression of CD31, CD34, IL-6, Fn, Collagen I, Talin, Paxillin, α3β1, podocin, nephrin, and B7-1.

Result: We found that renal function in the rat model of DN can be significantly improved by CTLA-4-Ig and CTLA-4-Ig + ultrasound microbubble treatment. Treatment efficacy was associated with reductions in renal parenchymal hardness, decreases in podocyte reduction, decreased IL-6, Fn and Collagen I expression, increased Talin, Paxillin and α3β1 expression, elevated podocin and nephrin expression, and decreased B7-1 expression. In contrast, these treatments did not impact CD31 or CD34 expression within the renal parenchyma.

Conclusion: These findings clearly emphasize that CTLA-4-Ig can effectively prevent podocyte damage, inhibiting inflammation and fibrosis, and thereby treating and preventing DN. In addition, ultrasound microbubble exposure can improve the ability of CTLA-4-Ig to pass through the glomerular basement membrane in order to access podocytes such that combination CTLA-4-Ig + microbubble exposure treatment is superior to treatment with CTLA-4-Ig only.
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http://dx.doi.org/10.18632/aging.202664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034886PMC
March 2021

Friendly mediates membrane depolarization-induced mitophagy in Arabidopsis.

Curr Biol 2021 May 11;31(9):1931-1944.e4. Epub 2021 Mar 11.

School of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address:

The oxidative environment within the mitochondria makes them particularly vulnerable to proteotoxic stress. To maintain a healthy mitochondrial network, eukaryotes have evolved multi-tiered quality control pathways. If the stress cannot be alleviated, defective mitochondria are selectively removed by autophagy via a process termed mitophagy. Despite significant advances in metazoans and yeast, in plants, the molecular underpinnings of mitophagy are largely unknown. Here, using time-lapse imaging, electron tomography, and biochemical assays, we show that uncoupler treatments cause loss of mitochondrial membrane potential and induce autophagy in Arabidopsis. The damaged mitochondria are selectively engulfed by autophagosomes that are labeled by ATG8 proteins in an ATG5-dependent manner. Friendly, a member of the clustered mitochondria protein family, is recruited to the damaged mitochondria to mediate mitophagy. In addition to the stress, mitophagy is also induced during de-etiolation, a major cellular transformation during photomorphogenesis that involves chloroplast biogenesis. De-etiolation-triggered mitophagy is involved in cotyledon greening, pointing toward an inter-organellar crosstalk mechanism. Altogether, our results demonstrate how plants employ mitophagy to recycle damaged mitochondria during stress and development.
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http://dx.doi.org/10.1016/j.cub.2021.02.034DOI Listing
May 2021

Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization.

bioRxiv 2021 Mar 2. Epub 2021 Mar 2.

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies, but also more resistant to neutralization by convalescent plasma (6.5 fold) and vaccinee sera (2.2-2.8 fold). The P.1 variant threatens current antibody therapies but less so the protective efficacy of our vaccines.
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http://dx.doi.org/10.1101/2021.03.01.433466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941628PMC
March 2021

Correction to: A cable-driven distal end-effector mechanism for single-port robotic surgery.

Int J Comput Assist Radiol Surg 2021 Apr;16(4):705

School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

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http://dx.doi.org/10.1007/s11548-021-02331-2DOI Listing
April 2021