Publications by authors named "Feng Wang"

4,906 Publications

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Clinical value of tumor-associated antigens and autoantibody panel combination detection in the early diagnostic of lung cancer.

Cancer Biomark 2021 Jun 19. Epub 2021 Jun 19.

Background: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer.

Methods: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer.

Results: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 211) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%.

Conclusions: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer.
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http://dx.doi.org/10.3233/CBM-210099DOI Listing
June 2021

High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma.

J Cancer 2021 4;12(15):4655-4660. Epub 2021 Jun 4.

Department of Gastroenterology, Shanghai Tenth people's hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai, 200072, P.R. China.

Despite recent improvements in the diagnosis and therapy of intrahepatic cholangiocarcinoma (ICC), the prognosis for ICC patients remains poor. Therefore, it is needed to identify new biological indicators for ICC progression. Immunohistochemistry was engaged to inspect the ecto-5'-nucleotidase (CD73) and CD8 expressions in tissue microarrays including tissues from 140 ICC patients. Then, the association between the level of CD73/CD8 and clinicopathologic characteristics of ICC was analysed. Finally, the prognostic value of CD73 and CD8 levels in ICC patients was assessed by Kaplan-Meier and multivariate and univariate analyses. The CD73 expression was evidently upregulated in ICC tissues compared to the corresponding peritumoral tissues. The elevated CD73 expression was positively related to the lymphatic metastasis (p=0.049). While the level of tumour-infiltrating CD8 T cells in tumour tissues was negatively associated with serum AFP (p=0.019), tumor size (p=0.028), and lymphatic metastasis (p=0.039). Additionally, patients with elevated CD73 expression or low tumour-infiltrating CD8 T cells exhibited shorter overall survival (OS) and higher disease-free survival (DFS) rates than patients with low CD73 expression and/or high tumour-infiltrating CD8 T cells. Notably, the overexpression of CD73 or low tumour-infiltrating CD8 T cells was an independent indicator for predicting the OS and DFS of ICC patients. We revealed that CD73 expression and low tumour-infiltrating CD8T cells are valuable predictors of survival and recurrence in patients with ICC.
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http://dx.doi.org/10.7150/jca.51038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210563PMC
June 2021

The application of aptamer Apt-236 targeting PvpA protein in the detection of antibodies against .

Anal Methods 2021 Jun 18. Epub 2021 Jun 18.

Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China.

Mycoplasma gallisepticum (M. gallisepticum) is the primary agent of chronic respiratory disease causing important economic losses in the poultry industry. Compared to antibodies, aptamers used to diagnose M. gallisepticum have many advantages, such as being chemically, animal-free produced and easily modifiable without affecting their affinity. Herein, a single-stranded DNA (ssDNA) aptamer Apt-236 which can specifically bind to PvpA protein of M. gallisepticum with a Kd of 1.30 ± 0.18 nM was selected successfully. An indirect blocking ELAA (ib-ELAA) for M. gallisepticum antibodies detection was also developed using Apt-236, in which M. gallisepticum antibodies would block the binding-position of aptamers. Therefor positive sera would prevent color development whereas negative sera will allow a strong color reaction. The ib-ELAA was consistent with other three widely used assays in terms of the growth and decline of the antibody response to M. gallisepticum, and showed substantial agreement with the results obtained using a commercial ELISA kit in clinical chicken sera samples. Therefore, the ib-ELAA developed in this study was a new format for aptamer application and would be an alternative method for the surveillance of M. gallisepticum.
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http://dx.doi.org/10.1039/d1ay00515dDOI Listing
June 2021

Therapeutic Exosomes in Prognosis and Developments of Coronary Artery Disease.

Front Cardiovasc Med 2021 31;8:691548. Epub 2021 May 31.

Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Exosomes, with an diameter of 30~150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD). Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.
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http://dx.doi.org/10.3389/fcvm.2021.691548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200468PMC
May 2021

N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver Tumorigenesis Differentially Regulating Ubiquitination of Targets.

Front Oncol 2021 31;11:681366. Epub 2021 May 31.

Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: A tremendous amount of studies have suggested that post-translational modifications (PTMs) play pivotal roles during tumorigenesis. Compared to other PTMs, lipid modification is less studied. Recently, N-myristoylation, one type of lipid modification, has been paid attention to the field of cancer. However, whether and how N-myristoylation exerts its roles in liver tumorigenesis still remains unclear.

Methods: Parallel reaction monitoring (PRM) was conducted to evaluate the expression of protein modification enzymes in paired tissues. Liver conditionally knocking NMT1 out mice model was used to assess the critical roles of N-myristoylation during liver tumorigenesis. Proteomics isobaric tags for relative and absolute quantification (iTraq) was performed to identify proteins that changed while NMT1 was knocked down. The click chemistry assay was used to evaluate the N-myristoylation levels of proteins.

Results: Here, N-myristolyation and its enzyme NMT1, but not NMT2, were found to be critical in liver cancer. Two categories of proteins, i.e., N-myristolyation down-regulated proteins (NDP, including LXN, RPL29, and FAU) and N-myristolyation up-regulated proteins (NUP, including AHSG, ALB, and TF), were revealed negatively and positively regulated by NMT1, respectively. Both NDP and NUP could be N-myristolyated by NMT1 indispensable of POTEE. However, N-myristolyation decreased and increased stability of NDP and NUP, respectively. Mechanistically, NDP-specific binding protein RPL7A facilitated HIST1H4H, which has ubiquitin E3 ligase function, to ubiquitinate NDP. By contrast, NUP-specific binding protein HBB prevented NUP from ubiquitination by HIST1H4H. Notably, function of RPL7A and HBB was all NMT1-dependent. Moreover, NDP suppressed while NUP stimulated transformative phenotypes. Clinically, higher levels of NMT1 and NUP with lower levels of NDP had worse prognostic outcome.

Conclusion: Collectively, N-myristolyation by NMT1 suppresses anti-tumorigenic NDP, whereas it stimulates pro-tumorigenic NUP by interfering their ubiquitination to finally result in a pro-tumorigenic outcome in liver cancer. Targeting N-myristolyation and NMT1 might be helpful to treat liver cancer.
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http://dx.doi.org/10.3389/fonc.2021.681366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201403PMC
May 2021

Donor clonal hematopoiesis increases risk of acute graft versus host disease after matched sibling transplantation.

Leukemia 2021 Jun 16. Epub 2021 Jun 16.

Department of Genomics Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.

Clonal hematopoiesis (CH) is associated with older age and an increased risk of myeloid malignancies and cardiovascular complications. We analyzed donor DNA samples in patients with AML/MDS who underwent first allogeneic stem cell transplant (SCT) to investigate the association between donor CH and transplant outcomes. We performed targeted deep sequencing of 300 genes on donor blood samples and identified CH with the minimum variant allele frequency of 2%. Among 363 donors, 65 (18%) had CH. The most frequently mutated genes were DNMT3A (31 of 65; 48%), TET2 (16 of 65; 25%), PPM1D (5 of 65, 8%), and ASXL1 (7 of 65; 11%). Transplant outcomes: time to neutrophil and platelet recovery, relapse incidence, transplant-related mortality and progression-free survival, were comparable by donor CH. However, risk of grade II-IV and III-IV acute graft versus host disease (aGvHD) at 6 months after transplant was higher with donor CH vs. without donor CH (hazard ratio (HR) = 2.4, 95% Confidence Interval (CI) = 1.6-3.6, p < 0.001 and HR = 3.8, 95% CI = 1.6-8.9, p = 0.003). In this homogenous population of AML/MDS patients, donor CH was associated with increased risk of grade II-IV and III-IV aGvHD. Further studies to investigate the mechanisms of increased aGvHD and therapeutic interventions to improve aGvHD in the context of donor CH are warranted.
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http://dx.doi.org/10.1038/s41375-021-01312-3DOI Listing
June 2021

Oxidation induced by dielectric barrier discharge (DBD) plasma treatment reduces IgG/IgE binding capacity and improves the functionality of glycinin.

Food Chem 2021 Jun 12;363:130300. Epub 2021 Jun 12.

College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China. Electronic address:

The effect of dielectric barrier discharge (DBD) plasma treatment times from 2 to 5 min at 40 kV on IgG/IgE binding capacity and functionality of soybean glycinin was examined. A substantial reduction in the binding capacity (91.64% for IgG and 81.49% for IgE) was obtained after 5 min of plasma treatment, as determined by western-blot and ELISA analyses. Further studies demonstrated that the elimination of antigenicity and allergenicity of glycinin was directly related to plasma-induced structural changes on two aspects. A conformational alteration caused by oxidation of peptide bond amino groups, accompanied with an oxidation of Trp, Tyr, and Phe amino acid residues, which was confirmed by surface hydrophobicity, multi-spectroscopic analysis, and amino acid analysis. The cleavage of polypeptide chains inevitably partially diminished the linear epitopes, resulting in a primary decline in IgG/IgE binding capacity. Additionally, an increase in the solubility from 10.78 ± 0.35 to 65.96 ± 1.86% and significant increase in the emulsifying ability from 21.08 ± 2.64 to 160.29 ± 4.12 m/g were observed after treatment of the plasma for 2 min. The present results confirm the potential use of DBD for the production of hypoallergenic soy protein-based products and improving their technical functions such as solubility and emulsifying ability.
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http://dx.doi.org/10.1016/j.foodchem.2021.130300DOI Listing
June 2021

Urinary triclosan in south China adults and implications for human exposure.

Environ Pollut 2021 Jun 9;286:117561. Epub 2021 Jun 9.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, China. Electronic address:

Triclosan (TCS) is widely applied in personal care products (PCPs) as an antimicrobial preservative. Due to its toxicity and potential risk to human health, TCS has attracted mounting concerns in recent years. However, biomonitoring of TCS in large human populations remains limited in China. In this study, 1163 adults in South China were recruited and urinary TCS concentrations were determined. TCS was detected in 99.5% of urine samples, indicating broad exposure in the study population. Urinary concentrations of TCS ranged from below the limit of detection (LOD) to 270 μg/L, with a median value of 3.67 μg/L. Urinary TCS concentrations from individuals were all lower than the Biomonitoring Equivalents reference dose, suggesting relatively low health risk in the participants. TCS concentrations did not differ significantly between sexes or education levels (p > 0.05). Nevertheless, marital status and age were found to be positively influence TCS levels (p < 0.001). After adjustment for body mass index (BMI), age was determined to be positively associated with TCS concentrations (p < 0.05), particularly in the age group from 31 to 51 years old. This study provides a baseline of urinary TCS exposure in South China general adult populations.
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http://dx.doi.org/10.1016/j.envpol.2021.117561DOI Listing
June 2021

Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells.

Med Sci Monit 2021 Jun 14;27:e930083. Epub 2021 Jun 14.

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).

BACKGROUND Helenalin is a pseudoguaianolide natural product with anti-cancer activities. This study investigated the underlying mechanism of the anti-prostate cancer effects of helenalin in vitro. MATERIAL AND METHODS CCK-8 assay was performed to detect the optimal concentrations of helenalin in DU145 and PC-3 cells. After exposure to helenalin and/or reactive oxygen species (ROS) inhibitor, ROS production was assessed by DCFH-DA staining. Thioredoxin reductase-1 (TrxR1) expression was detected by RT-qPCR and western blot. Moreover, apoptosis and cell cycle were evaluated by flow cytometry. Following TrxR1 knockdown or overexpression, TrxR1 expression, ROS generation, apoptosis, cell cycle, migration, and invasion were examined in cells co-treated with helenalin. RESULTS Helenalin distinctly repressed the viability of prostate cancer cells in a concentration-dependent manner. We chose 8 μM and 4 μM as the optimal concentrations of helenalin for DU145 and PC-3 cells, respectively. Helenalin treatment markedly triggered ROS production and lowered TrxR1 expression, which was ameliorated by ROS inhibitor. Exposure to helenalin facilitated apoptosis as well as G0/G1 cell cycle arrest, which was reversed by ROS inhibitor. Helenalin relieved the inhibitory effect of TrxR1 on ROS production. Furthermore, helenalin ameliorated the decrease in apoptosis rate and the shortening of G0/G1 phase as well as the increase in migration and invasion induced by TrxR1 overexpression. CONCLUSIONS Our findings revealed that helenalin accelerated ROS-mediated apoptosis and cell cycle arrest via targeting TrxR1 in human prostate cancer cells.
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http://dx.doi.org/10.12659/MSM.930083DOI Listing
June 2021

Comprehensive Analysis and Identification of Key Driver Genes for Distinguishing Between Esophageal Adenocarcinoma and Squamous Cell Carcinoma.

Front Cell Dev Biol 2021 28;9:676156. Epub 2021 May 28.

Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

Esophageal cancer (EC) is one of the deadliest cancers in the world. However, the mechanism that drives the evolution of EC is still unclear. On this basis, we identified the key genes and molecular pathways that may be related to the progression of esophageal adenocarcinoma and squamous cell carcinoma to find potential markers or therapeutic targets. GSE26886 were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) among normal samples, EA, and squamous cell carcinoma were determined using R software. Then, potential functions of DEGs were determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The STRING software was used to identify the most important modules in the protein-protein interaction (PPI) network. The expression levels of hub genes were confirmed using UALCAN database. Kaplan-Meier plotters were used to confirm the correlation between hub genes and outcomes in EC. In this study, we identified 1,098 genes induced in esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC), and 669 genes were reduced in EA and ESCC, suggesting that these genes may play an important role in the occurrence and development of EC tumors. Bioinformatics analysis showed that these genes were involved in cell cycle regulation and p53 and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In addition, we identified 147 induced genes and 130 reduced genes differentially expressed in EA and ESCC. The expression of ESCC in the EA group was different from that in the control group. By PPI network analysis, we identified 10 hub genes, including GNAQ, RGS5, MAPK1, ATP1B1, HADHA, HSDL2, SLC25A20, ACOX1, SCP2, and NLN. TCGA validation showed that these genes were present in the dysfunctional samples between EC and normal samples and between EA and ESCC. Kaplan-Meier analysis showed that MAPK1, ACOX1, SCP2, and NLN were associated with overall survival in patients with ESCC and EA. In this study, we identified a series of DEGs between EC and normal samples and between EA and ESCC samples. We also identified 10 key genes involved in the EC process. We believe that this study may provide a new biomarker for the prognosis of EA and ESCC.
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http://dx.doi.org/10.3389/fcell.2021.676156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194272PMC
May 2021

The Interaction Between Microglia and Macroglia in Glaucoma.

Front Neurosci 2021 28;15:610788. Epub 2021 May 28.

Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.
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http://dx.doi.org/10.3389/fnins.2021.610788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193936PMC
May 2021

[Tc]Tc-Galacto-RGD integrin αβ-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data.

EJNMMI Res 2021 Jun 13;11(1):59. Epub 2021 Jun 13.

Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [Tc]Tc-Galacto-RGD single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αβ expression, and neovascularization in lung cancer subtypes was also addressed.

Methods: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [Tc]Tc-Galacto-RGD imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [Tc]Tc-Galacto-RGD was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αβ, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours.

Results: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [Tc]Tc-Galacto-RGD SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αβ expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αβ expression. Integrin αβ expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αβ expression.

Conclusions: [Tc]Tc-Galacto-RGD SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.
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http://dx.doi.org/10.1186/s13550-021-00801-xDOI Listing
June 2021

Linking genomic and physiological characteristics of psychrophilic Arthrobacter to metagenomic data to explain global environmental distribution.

Microbiome 2021 Jun 12;9(1):136. Epub 2021 Jun 12.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, 2052, China.

Background: Microorganisms drive critical global biogeochemical cycles and dominate the biomass in Earth's expansive cold biosphere. Determining the genomic traits that enable psychrophiles to grow in cold environments informs about their physiology and adaptive responses. However, defining important genomic traits of psychrophiles has proven difficult, with the ability to extrapolate genomic knowledge to environmental relevance proving even more difficult.

Results: Here we examined the bacterial genus Arthrobacter and, assisted by genome sequences of new Tibetan Plateau isolates, defined a new clade, Group C, that represents isolates from polar and alpine environments. Group C had a superior ability to grow at -1°C and possessed genome G+C content, amino acid composition, predicted protein stability, and functional capacities (e.g., sulfur metabolism and mycothiol biosynthesis) that distinguished it from non-polar or alpine Group A Arthrobacter. Interrogation of nearly 1000 metagenomes identified an over-representation of Group C in Canadian permafrost communities from a simulated spring-thaw experiment, indicative of niche adaptation, and an under-representation of Group A in all polar and alpine samples, indicative of a general response to environmental temperature.

Conclusion: The findings illustrate a capacity to define genomic markers of specific taxa that potentially have value for environmental monitoring of cold environments, including environmental change arising from anthropogenic impact. More broadly, the study illustrates the challenges involved in extrapolating from genomic and physiological data to an environmental setting. Video Abstract.
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http://dx.doi.org/10.1186/s40168-021-01084-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196931PMC
June 2021

A risk score system for predicting complicated appendicitis and aid decision-making for antibiotic therapy in acute appendicitis.

Ann Palliat Med 2021 May 24. Epub 2021 May 24.

Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.

Background: Exclusive antibiotic therapy is a feasible treatment option for uncomplicated appendicitis, but the pre-treatment diagnosis of uncomplicated appendicitis is challenging. This study aimed to develop a risk score system to predict complicated appendicitis and aiding decision-making regarding antibiotic therapy for acute appendicitis.

Methods: The risk score system for predicting complicated appendicitis was constructed and validated by a surgical therapy cohort (n=543). Furthermore, we applied an independent antibiotic treatment cohort (n=169) to verify whether the risk score system could guide antibiotic treatment decision-making in patients with acute appendicitis (AA).

Results: A total of 543 patients were included in the surgical therapy cohort and was split into the primary (n=375) and validation (n=168) cohorts with repeated random sampling. In the primary cohort, multivariate analysis confirmed that periappendiceal fat stranding (PFS, P<0.001, OR =67.80), the C-reactive protein level (CRP ≥38 mg/L, P<0.001, OR =5.77) and the neutrophil-to-lymphocyte ratio (NLR ≥7, P<0.001, OR =3.51) were independent risk factors for complicated appendicitis. The PFS, CRP and NLR scores were 10.0, 4.0 and 3.0 points, respectively. Fourteen patients (3.7%, 14/375) and seven patients (4.2%, 7/168) with pathologically confirmed complicated appendicitis were classified as having uncomplicated appendicitis in the primary and validation cohorts based on the risk score system, respectively. In the independent antibiotic treatment cohort (n=169), the failure rate of antibiotic treatment was 49.2% and 5.3% for the risk score system predicted complicated AA and uncomplicated AA. Furthermore, the predictive accuracy of the risk score system for antibiotic treatment failure as measured by the area under the curve (AUC) was 0.823 (95% CI: 0.757-0.878).

Conclusions: We found that the proposed risk score system based on biological and CT features not only enables the accurate identification of complicated appendicitis patients before pre-treatment but also serves to guide antibiotic treatment decisions.
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http://dx.doi.org/10.21037/apm-21-26DOI Listing
May 2021

Managing Defects Density and Interfacial Strain via Underlayer Engineering for Inverted CsPbI Br Perovskite Solar Cells with All-Layer Dopant-Free.

Small 2021 Jun 12:e2101902. Epub 2021 Jun 12.

Soochow Institute for Energy and Materials Innovation (SIEMIS), School of Energy, Soochow University, Suzhou, 215006, China.

Inorganic perovskite CsPbI Br has advantages of excellent thermal stability and reasonable bandgap, which make it suitable for top layer of tandem solar cells. Nevertheless, solution-processed all-inorganic perovskites generally suffer from high-density defects as well as significant tensile strain near underlayer/perovskite interface, both leading to compromised device efficiency and stability. In this work, the defect density as well as interfacial tensile strain in inverted CsPbI Br perovskite solar cells (PeSCs) is remarkably reduced by using a bilayer underlayer composed of dopant-free 2,2',7,7'-tetrakis(N,N-dip-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) and copper phthalocyanine 3,4',4″,4'″-tetrasulfonated acid tetrasodium salt (TS-CuPc) nanoparticles. As compared to control devices with pristine Spiro-OMeTAD, devices based on Spiro-OMeTAD/TS-CuPc exhibit remarkably improved photovoltaic performance and enhanced thermal/humidity stability due to the better perovskite crystallization, improved interfacial passivation, and hole-collection as well as efficient interfacial strain release. As a result, a champion efficiency of 14.85% can be achieved, which is approaching to the best reported for dopant-free and inverted all-inorganic PeSCs. The work thus provides an efficient strategy to simultaneously regulate the defects density and strain issue related to inorganic perovskites.
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http://dx.doi.org/10.1002/smll.202101902DOI Listing
June 2021

Clonal Dynamics and clinical implications of Post-Remission Clonal Hematopoiesis in Acute Myeloid Leukemia (AML).

Blood 2021 Jun 3. Epub 2021 Jun 3.

The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.

While clonal hematopoiesis (CH) can precede the development of acute myeloid leukemia (AML), it can also persist after achieving remission. Long-term clonal dynamics and clinical implications of persistent CH are not well understood. Here, we studied the prevalence, dynamics and clinical implications of post-remission CH in 164 AML patients who attained complete remission after induction chemotherapies. Post-remission CH was identified in 79 (49%) patients. Post-remission CH persisted long-term in 91% of the trackable patients despite treatment with various types of consolidation and maintenance therapies. Post-remission CH was eradicated in 20 out of 21 (95%) patients who underwent allogeneic stem cell transplant. While patients with post-remission CH as a group had comparable hematopoiesis with those without it, patients with persistent TET2 mutations showed significant neutropenia long-term. Post-remission CH had little impact on relapse risk, non-relapse mortality, and incidence of atherosclerotic cardiovascular disease, although the clinical impact of post-CR CH was heterogeneous among different mutations. These data suggest that while residual clonal hematopoietic stem cells (HSCs) are generally resistant to consolidation and maintenance therapies, they retain the ability to maintain normal hematopoiesis and have little impact on clinical outcomes, although larger study is needed to dissect the gene-specific heterogeneity.
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http://dx.doi.org/10.1182/blood.2020010483DOI Listing
June 2021

Clinical Outcomes of Immediate Implant Loading with Fixed Prostheses in Edentulous Maxillae: A Systematic Review.

Int J Oral Maxillofac Implants 2021 May-Jun;36(3):503-519

Purpose: To review the evidence from the clinical outcomes of immediately loaded implants with fixed prostheses in edentulous maxillae.

Materials And Methods: An electronic search was performed in PubMed/MEDLINE, Embase, and Cochrane to identify studies investigating the outcome of implants subjected to immediate loading with fixed dental prostheses in edentulous maxillae. Only clinical studies with more than 10 patients and a mean follow-up time of more than 12 months were included. Meta-analysis was utilized to compare the clinical outcomes between immediately loaded implants and conventionally loaded implants. For immediately loaded implants, a cumulative implant survival rate (ISR) was weighted by the duration of follow-up and number of implants. The weighted marginal bone loss (MBL) was also assessed.

Results: A total of 33 studies (16 retrospective studies and 17 prospective studies) were included, which involved 2,635 patients and 12,480 implants. Meta-analysis did not reveal a significant difference of ISR or MBL between the two loading groups. For immediately loaded implants, the weighted cumulative ISR was 95.53% (median: 97.50%) with a mean follow-up of 46.07 months (SD: 30.92). Fourteen studies reported on the MBL of implants, and the mean MBL was 1.19 mm (SD: 0.88) with a mean period of 57.70 months (SD: 32.56). The results should be interpreted with caution due to the lack of randomized controlled trials (RCTs) and the heterogeneity of the data.

Conclusion: Despite the lack of RCTs, immediate implant loading with a fixed prosthesis in the edentulous maxilla seems to be a reliable treatment alternative with a high ISR, when appropriate inclusion/exclusion criteria are followed.
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http://dx.doi.org/10.11607/jomi.8509DOI Listing
June 2021

Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy.

J Nanobiotechnology 2021 Jun 10;19(1):175. Epub 2021 Jun 10.

Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

Background: Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies.

Methods: We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (Cu-NOTA-DBCO) using bioorthogonal chemistry. Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi).

Results: CTLs can be stably radiolabeled with Cu with a minimal effect on cell viability. PET imaging of Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms.

Conclusion: These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens.
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http://dx.doi.org/10.1186/s12951-021-00924-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194184PMC
June 2021

Emodin inhibits lipid accumulation and inflammation in adipose tissue of high-fat diet-fed mice by inducing M2 polarization of adipose tissue macrophages.

FASEB J 2021 Jul;35(7):e21730

Department of Nutrition and Food Hygiene & Department of Health Education and Health Management, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi'an, China.

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD-fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin-treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin-induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.
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http://dx.doi.org/10.1096/fj.202100157RRDOI Listing
July 2021

[The feasibility of zygomatic implant quad approach in patients with tooth agenesis: a radiographic analysis].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):196-200

Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology. Shanghai 200011, China.

Purpose: The aim of this study was to analyze the feasibility of zygomatic implant quad approach in patients with tooth agenesis.

Methods: Based on the data from cone-beam CT (CBCT), twenty one patients with tooth agenesis who were planned to receive zygomatic implant quad approach were enrolled. The radiographic bone-to-implant contact (rBIC) of each zygomatic implant placed virtually in patients' zygomatic segment was measured. SPSS 25.0 software package was used for statistical analysis.

Results: Twenty patients' plans of zygomatic implant quad approach were completed (12 men and 8 women). A total of 80 zygomatic implants were placed virtually and the average rBIC of zygomatic segment was (13.85±3.29) mm. The rBIC values of 40 mesial zygomatic implants and 40 distal zygomatic implants were (13.80±3.74) mm and (13.90±2.81) mm, respectively(P>0.05). The average rBIC in male of 24 mesial zygomatic implants and 24 distal zygomatic implants were(14.21±4.08) mm and(14.31±3.18) mm, respectively, slightly higher than those in female of 16 mesial zygomatic implants and 16 distal zygomatic implants, which were (13.18±3.18) mm and (13.29±2.10) mm, respectively. There was no significant difference between the two groups (P>0.05). The average rBIC of 15 extra sinus zygomatic implants, 46 against sinus lateral wall zygomatic implants and 19 intra-sinus zygomatic implants were (16.27±2.95), (13.87±3.10) and (11.88±2.78) mm, respectively. There was significant difference between the extra sinus zygomatic implants and the other two(P<0.05).

Conclusions: It is feasible to plan zygomatic implant quad approach for patients with tooth agenesis. Zygomatic implants can get adequate rBIC in zygomatic segment and to provide sufficient support and retention of the superstructure.
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April 2021

Structural and Electrochemical Investigation of Crystallite Size Controlled Zinc Ferrite (ZnFe2O4).

Nanotechnology 2021 Jun 9. Epub 2021 Jun 9.

Department of Materials Science & Engineering, Stony Brook University, Stony Brook, New York, UNITED STATES.

Zinc ferrite, ZnFe2O4 (ZFO), is a promising electrode material for next generation Li-ion batteries because of its high theoretical capacity and low environmental impact. In this report, synthetic control of crystallite size from nanometer to submicron scale enabled probing of the relationships between ZFO size and electrochemistry. A facile two-step coprecipitation and annealing method was used to prepare ZFO with sizes ranging ~9 nm to > 200 nm. Complementary synchrotron and electron microscopy techniques were used to characterize the materials. Increasing the annealing temperature increased crystallinity and decreased microstrain, while local structural ordering was maintained independent of crystallite size. Electrochemical characterization revealed that the smaller sized materials delivered higher capacities during initial lithiation. Larger sized particles exhibited a lack of distinct electrochemical signatures above 1.0 V, suggesting that the longer diffusion length associated with greater crystallite size causes the lithiation process to proceed via non-discrete lithium insertion, cation migration, and conversion processes. Notably, larger particles exhibited enhanced electrochemical reversibility over 50 cycles at a C/2 rate. This intriguing result was probed through XAS and XPS measurements of the cycled electrodes. XAS revealed that the larger crystallite size materials do not completely convert to Fe0 during the first lithiation and that independent of size, delithiation results in the formation of nanocrystalline FeO and ZnO phases rather than ZnFe2O4. After 20 cycles, the larger crystallites showed reversibility between partially oxidized FeO in the charged state and Fe0 in the discharged state, while the smaller sized material was electrochemically inactive as Fe0. XPS analysis revealed more significant SEI formation on the cycled electrodes utilizing ZFO with smaller crystallite size. This finding suggests that excessive SEI buildup on the smaller sized, higher surface area ZFO particles contributes to their reduced electrochemical reversibility relative to the larger crystallite size materials.
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http://dx.doi.org/10.1088/1361-6528/ac09a9DOI Listing
June 2021

Graphene Electric Field Sensor Enables Single Shot Label-Free Imaging of Bioelectric Potentials.

Nano Lett 2021 Jun 8. Epub 2021 Jun 8.

Department of Physics, University of California Berkeley, Berkeley, California 94720, United States.

The measurement of electrical activity across systems of excitable cells underlies current progress in neuroscience, cardiac pharmacology, and neurotechnology. However, bioelectricity spans orders of magnitude in intensity, space, and time, posing substantial technological challenges. The development of methods permitting network-scale recordings with high spatial resolution remains key to studies of electrogenic cells, emergent networks, and bioelectric computation. Here, we demonstrate single-shot and label-free imaging of extracellular potentials with high resolution across a wide field-of-view. The critically coupled waveguide-amplified graphene electric field (CAGE) sensor leverages the field-sensitive optical transitions in graphene to convert electric potentials into the optical regime. As a proof-of-concept, we use the CAGE sensor to detect native electrical activity from cardiac action potentials with tens-of-microns resolution, simultaneously map the propagation of these potentials at tissue-scale, and monitor their modification by pharmacological agents. This platform is robust, scalable, and compatible with existing microscopy techniques for multimodal correlative imaging.
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http://dx.doi.org/10.1021/acs.nanolett.1c00543DOI Listing
June 2021

Facile Synthesis of Polyphenothiazine as a High-Performance p-Type Cathode.

ChemSusChem 2021 Jun 8. Epub 2021 Jun 8.

Wuhan University, Bayi Road, CHINA.

p-Type electroactive polymers are promising cathodes for dual-ion batteries but cost-effective candidates are still lacking. Herein, we have synthesized a novel p-type polymer, namely polyphenothiazine (PPTZ), by a facile one-step oxidation polymerization from the low-cost phenothiazine (PTZ) monomer. As a cathode for rechargeable lithium batteries, PPTZ showed superior electrochemical performance to previously reported PTZ-based polymers with complicated structure and synthesis. For instance, it achieved a high reversible capacity of 157 mAh g -1 within 2.5-4.3 V vs. Li + /Li with an average discharge voltage of 3.5 V, and a high capacity retention of 77% after 500 cycles. The highly reversible one-electron redox mechanism of PPTZ was also detailedly investigated by electrochemical tests, ex-situ FT-IR and XPS characterizations, and DFT calculations. We believe PPTZ will become an attractive p-type cathode material toward practical applications, and the facile synthesis may be also extended to other polymer cathodes based on N-heteroaromatic units.
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http://dx.doi.org/10.1002/cssc.202101008DOI Listing
June 2021

Optimal Implantation Site of Orthodontic Micro-Screws in the Mandibular Anterior Region Based on CBCT.

Front Physiol 2021 20;12:630859. Epub 2021 May 20.

The Sixth Medical Center of PLA General Hospital, Beijing, China.

To determine the optimal implantation site of orthodontic micro-screws based on cone beam computed tomography (CBCT) analysis in the mandibular anterior tooth region, provide a theoretical basis for orthodontic implant placement and improve post-implantation stability. Forty patients who underwent CBCT scanning were selected for this study. CBCT scanning was applied to measure the interradicular distance, buccolingual dimension, labial cortical bone thickness and lingual cortical bone thickness between mandibular anterior teeth at planes 2, 4, 6, and 8 mm below the alveolar ridge crest. The data were measured and collected to obtain a comprehensive evaluation of the specific site conditions of the alveolar bone. The interradicular distance, buccolingual dimension and labial cortical bone thickness between the mandibular anterior teeth were positively correlated with the distance below the alveolar ridge crest (below 8 mm). The interradicular distance, buccolingual dimension, labial cortical bone thickness, and lingual cortical bone thickness were all greater than those in other areas between the lateral incisor root and canine incisor root 4, 6, and 8 mm below the alveolar ridge crest. The area between the lateral incisor root and the canine incisor root in planes 4, 6, and 8 mm from the alveolar ridge crest can be used as safe sites for implantation, while 8 mm below the alveolar ridge crest can be the optimal implantation site. An optimal implantation site can be 8 mm below the alveolar ridge crest between the lateral incisor root and the canine incisor root.
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http://dx.doi.org/10.3389/fphys.2021.630859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173216PMC
May 2021

Analgesia effects of IPACK block added to multimodal analgesia regiments after total knee replacement: A systematic review of the literature and meta-analysis of 5 randomized controlled trials.

Medicine (Baltimore) 2021 Jun;100(22):e25884

Department of Orthopedics, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China.

Background: Currently, no meta-analysis exists elucidate the analgesic effect of adding IPACK block to our current multimodal analgesia regimen after total knee replacement (TKR). The purpose of this study is to systematically review the level I evidence in the literature to ascertain whether IPACK block can bring additional analgesic benefits to existing multimodal analgesia regimens.

Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Only level I randomized controlled trials (RCTs) were included in our study. The primary outcome was the pain scores with rest and activity. Secondary outcomes included cumulative opioid consumption, cumulative distance ambulated, and length of stay (LOS).

Results: Five RCTs with a total of 467 patients were included. The most important finding in our study was that although IPACK block supplementation improved pain scores at 12 hours with rest or activity after surgery, no such benefit was observed at subsequent time points during the postoperative period. Interestingly, IPACK supplementation did not reduce opioid consumption, especially in the first 24 hours after surgery. Furthermore, other postoperative outcomes, including cumulative distance ambulated and LOS, were also not improved by the addition of an IPACK.

Conclusions: The addition of an IPACK block to multimodal analgesia regiments does not reduce the postoperative opioid consumption nor improve functional performance. However, it may be an appropriate method to improve immediate analgesic effects after TKR.
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http://dx.doi.org/10.1097/MD.0000000000025884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183733PMC
June 2021

Palladium-Catalyzed C-H Allylation of Electron-Deficient Polyfluoroarenes with gem-Difluorinated Cyclopropanes.

Org Lett 2021 Jun 4;23(12):4920-4924. Epub 2021 Jun 4.

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453000, P. R. China.

A palladium-catalyzed C-H allylation of electron-deficient polyfluoroarenes with gem-difluorinated cyclopropanes is reported. It provides a useful and facile approach to 2-fluoroallylic polyfluoroarenes in moderate to excellent yields with high Z-selectivity. In addition, this new approach has good functional group compatibility and broad substrate scope.
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http://dx.doi.org/10.1021/acs.orglett.1c01699DOI Listing
June 2021

PLEK2 promotes osteosarcoma tumorigenesis and metastasis by activating the PI3K/AKT signaling pathway.

Oncol Lett 2021 Jul 18;22(1):534. Epub 2021 May 18.

Department of Orthopedics, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.

Increasing evidence suggest that pleckstrin-2 (PLEK2) acts as an oncogene in several malignancies. The present study aimed to investigate the effects of PLEK2 on osteosarcoma (OS) tumorigenesis and metastasis. PLEK2 expression in OS was analyzed via bioinformatics, reverse transcription-quantitative PCR, western blot and immunohistochemistry analyses. The Cell Counting Kit-8 (CCK-8), colony formation and EdU assays were performed to assess the role of PLEK2 in OS cell proliferation. The pro-metastatic effects of PLEK2 were assessed via the Transwell and wound healing assays. In addition, the PLEK2 downstream pathway was analyzed via bioinformatics analysis and verified via western blot analysis. The results demonstrated that PLEK2 expression was upregulated in both OS cell lines and specimens. The results of the CCK-8, colony formation and EdU assays demonstrated that PLEK2 promoted OS cell proliferation . The experiments further demonstrated that PLEK2 knockdown significantly suppressed OS growth. In addition, the Transwell and wound healing assays indicated that PLEK2 promoted OS invasiveness , which was induced by the activation of the epithelial-to-mesenchymal transition process. Bioinformatics analysis revealed that PLEK2 can activate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, which was verified via western blot analysis. Taken together, the results of the present study suggest that PLEK2 may play a tumor-promoting role in OS via the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.3892/ol.2021.12795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161470PMC
July 2021

An enhanced open sandwich immunoassay by molecular evolution for noncompetitive detection of Alternaria mycotoxin tenuazonic acid.

Food Chem 2021 Nov 13;361:130103. Epub 2021 May 13.

Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Open sandwich enzyme-linked immunosorbent assay (OS-ELISA), a novel noncompetitive immunoassay format, has shown great potential in rapid detection for small molecules compared with traditional competitive format. Here, an enhanced OS-ELISA towards the mycotoxin tenuazonic acid (TeA) was developed for the first time based on heavy chain variable region (V) and light chain variable region (V) from the hybridoma cells (3F10) producing anti-TeA monoclonal antibody (mAb). The established OS-ELISA exhibited a limit of detection of 0.08 ng/mL, and was 13 times more sensitive than mAb-based indirect competitive ELISA (ic-ELISA). The proposed assay was also applied to detect TeA contents in juice, flour and tomato ketchup samples with satisfactory recoveries of 87.6%-111.3%. Finally, the great accuracy of the established OS-ELISA method was validated by the standard ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS).
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http://dx.doi.org/10.1016/j.foodchem.2021.130103DOI Listing
November 2021

Plasmonic-doped melanin-mimic for CXCR4-targeted NIR-II photoacoustic computed tomography-guided photothermal ablation of orthotopic hepatocellular carcinoma.

Acta Biomater 2021 May 31. Epub 2021 May 31.

Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Institute of Digital Intelligence of Zhujiang Hospital of Southern Medical University, Guangzhou, 510280, China; Guangdong Provincial Clinical and Engineering Technology Center of Digital Medicine, Guangzhou, 510280, China. Electronic address:

Effective and noninvasive diagnosis and prompt treatment of early-stage hepatocellular carcinoma (HCC) are urgently needed to reduce its mortality rate. Herein, the integration of high-resolution diagnostic second near-infrared (NIR-II) photoacoustic computed tomography (PACT) and imaging-guided targeted photothermal ablation of orthotopic small HCC (SHCC) is presented for the first time, which was enabled by a plasmonic platinum (Pt)-doped polydopamine melanin-mimic nanoagent. As designed, an antibody-modified nanoagent (designated [email protected]) with a plasmonic blackbody-like NIR absorption and superior photothermal conversion efficiency (71.3%) selectively targeted and killed CXCR4-overexpressing HCC (HepG2) cells, which was validated in in vitro experiments. The targeted accumulation properties of [email protected] in vivo were previously recognized by demonstrating effective NIR-II PA imaging and photothermal ablation in a subcutaneous HCC mouse model. Subsequently, with real-time quantitative guidance by PACT for the accurate diagnosis of intraabdominal SHCC (approximately 4 mm depth), the effective and noninvasive photothermal ablation of SHCCs was successfully demonstrated in an orthotopic tumor-bearing mouse model without damaging adjacent liver tissues. These results show a great potential of NIR-II PACT-guided noninvasive photothermal therapy as an innovative phototheranostic approach and expand the biomedical applications of melanin-mimic materials. STATEMENT OF SIGNIFICANCE: In this paper, we report the first diagnostic NIR-II photoacoustic computed tomography (PACT)-guided noninvasive photothermal ablation of small hepatocellular carcinoma (SHCC) located in deep tissues in orthotopic tumor-bearing mice; this process is empowered by a polydopamine-based melanin-mimic tumor-targeting nanoagent doped with plasmonic platinum that provides superior NIR-II (1064 nm) absorption and photothermal conversion efficiency of 71.3%. Following surface modification with anti-CXCR4 antibodies, the nanoagent (namely [email protected]) can selectively target CXCR4-overexpressed HepG2 carcinoma cells and tumor lesions, and serve as the theranostic agent for both NIR-II PACT-based diagnosis of orthotopic SHCC (diameter less than 5 mm) and efficient NIR-II PTT in vivo. This study may also extend the potential of melanin-derived blackbody materials for optical-biomedical and water distillation applications.
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http://dx.doi.org/10.1016/j.actbio.2021.05.034DOI Listing
May 2021

[F]FEDAC translocator protein positron emission tomography-computed tomography for early detection of mitochondrial dysfunction secondary to myocardial ischemia.

Ann Nucl Med 2021 Jun 3. Epub 2021 Jun 3.

Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.

Background: This study aimed to evaluate the biodistribution and kinetics of [F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI).

Methods: The radiochemical purity and stability of [F]FEDAC were analyzed by radio-high-performance liquid chromatography (radio-HPLC). Its biodistribution and kinetics were evaluated by dissection and dynamic imaging using micro-positron emission tomography-computed tomography (micro-PET-CT) in healthy mice. [F]FEDAC was also applied in an MI rat model and in sham-operated controls. Mitochondrial changes were observed by immunohistochemical staining and electron microscopy.

Results: Radioactivity levels (%ID/g) in the myocardium in normal mice, determined by [F]FEDAC, were 8.32 ± 0.80 at 5 min and 2.40 ± 0.10 at 60 min. PET showed significantly decreased uptake by injured cardiac tissue in MI rats, with maximal normal-to-ischemic uptake ratios of 10.47 ± 3.03 (1.5 min) and 3.92 ± 1.12 (27.5 min) (P = 0.025). Immunohistochemistry confirmed that TSPO expression was decreased in MI rats. Mitochondrial ultrastructure demonstrated significant swelling and permeability.

Conclusion: [F]FEDAC uptake is reduced in the injured myocardium, consistent with mitochondrial dysfunction. These results may provide new evidence to aid the early detection of mitochondrial dysfunction associated with myocardial ischemic injury.
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http://dx.doi.org/10.1007/s12149-021-01630-7DOI Listing
June 2021