Publications by authors named "Yi-Ting Wang"

164 Publications

Interactive rather than independent effect of and sex potentiates tau deposition in women.

Brain Commun 2021 7;3(2):fcab126. Epub 2021 Jun 7.

Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, McGill University, Montréal, QC, Canada.

The apolipoprotein E gene () is the most important genetic risk factor for sporadic Alzheimer disease, with the allele being associated with increased cerebral amyloid-β and tau pathologies. Although has been suggested to have a stronger effect in women as compared to men, there is a lack of comprehensive assessment on how the interactive effect of and sex modulates regional vulnerability to tau accumulation. We previously have shown the regional vulnerability to the interactive effect of tau and , yet the sex difference was not specifically addressed. In this study, we leveraged PET imaging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University Research Centre for Studies in Aging to elucidate the by-sex interactive effect on tau burden. We hypothesized sex-dependent regional vulnerability to tau deposition. PET radiopharmaceuticals [F]AZD4694 and [F]MK6240 were used to assess amyloid-β and tau level respectively in 277 subjects from the Translational Biomarkers in Aging and Dementia cohort. We found that the interaction between and sex, rather than their independent main effects, was associated with abnormal tau accumulation in medial temporal regions. Specifically, we found that female carriers showed significantly higher tau burden in early tau deposition regions including the hippocampus, entorhinal and parahippocampal cortices, after accounting for age, educational attainment, clinical diagnosis and neocortical amyloid load. We replicated these findings in 221 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort, in which a different tau-PET radioligand, [F]flortaucipir, was used to assess tau burden. In conclusion, this study provides evidence from two cohort studies that interactive rather than independent effect of and sex potentiates early tau deposition in women. Our results have important implications for clinical trials and practice, which should take into consideration both carriage status and sex for identifying individuals with the highest probability of developing tau accumulation and clinical progression.
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http://dx.doi.org/10.1093/braincomms/fcab126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226193PMC
June 2021

The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance.

Cancer Cell 2021 Jul 24;39(7):999-1014.e8. Epub 2021 Jun 24.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA; Department of Cell, Development, & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.

Our study details the stepwise evolution of gilteritinib resistance in FLT3-mutated acute myeloid leukemia (AML). Early resistance is mediated by the bone marrow microenvironment, which protects residual leukemia cells. Over time, leukemia cells evolve intrinsic mechanisms of resistance, or late resistance. We mechanistically define both early and late resistance by integrating whole-exome sequencing, CRISPR-Cas9, metabolomics, proteomics, and pharmacologic approaches. Early resistant cells undergo metabolic reprogramming, grow more slowly, and are dependent upon Aurora kinase B (AURKB). Late resistant cells are characterized by expansion of pre-existing NRAS mutant subclones and continued metabolic reprogramming. Our model closely mirrors the timing and mutations of AML patients treated with gilteritinib. Pharmacological inhibition of AURKB resensitizes both early resistant cell cultures and primary leukemia cells from gilteritinib-treated AML patients. These findings support a combinatorial strategy to target early resistant AML cells with AURKB inhibitors and gilteritinib before the expansion of pre-existing resistance mutations occurs.
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http://dx.doi.org/10.1016/j.ccell.2021.06.003DOI Listing
July 2021

Two new cytotoxic cycloartane triterpenoids from (Wall.) R. N. Parker.

Nat Prod Res 2021 Jun 8:1-6. Epub 2021 Jun 8.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P.R. China.

Two new cycloartane triterpenoids, (24 )-cycloartane-3,24,25,30-tetrol () and (24 )-24,25,30-trihydroxy-9,19-cycloartane-3-one (), along with three known compounds () were isolated from leaves and twigs of . The new compounds were elucidated based on comprehensive spectroscopic analysis, including 1 D, 2 D NMR and HREIMS. The in vitro cytotoxic activities evaluation of five human cancer cell lines revealed that compound exhibited cytotoxic activity on all of tested human cancer cell lines, while compound only had specific activity on SMMC-7721 cell line.
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http://dx.doi.org/10.1080/14786419.2021.1906242DOI Listing
June 2021

Construction and Validation of Novel Nomograms for Predicting Prognosis of Pancreatic Ductal Adenocarcinoma After Surgery According to Different Primary Cancer Locations.

Front Oncol 2021 23;11:646082. Epub 2021 Apr 23.

Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.

Background/aims: Pancreatic ductal adenocarcinoma (PDAC) can occur in different parts of the pancreas. This study aimed to identify clinicopathological characteristics independently correlated with the prognosis of PDAC of the pancreatic head/uncinate (PHC) or body-tail (PBTC), and to develop novel nomograms for predicting cancer-specific survival (CSS) according to different primary cancer locations.

Methods: 1160 PDAC patients were retrospectively enrolled and assigned to training and test sets with each set divided into PHC and PBTC groups. Comparative analysis of clinicopathologic characteristics, survival analysis, and multivariate analysis were performed. Independent factors were identified and used for constructing nomograms. The performance of the nomograms was validated in the test set.

Results: Primary tumor location was an independent risk factor for prognosis of PDAC after surgery. Specially, gender, fasting blood glucose, and preoperative cancer antigen 19-9 were significantly associated with prognosis of PHC, whereas age, body mass index, and lymph nodes were significantly correlated with the prognosis of PBTC. A significant difference in prognosis was found between PHC and PBTC in stage Ia and stage III. Three nomograms were established for predicting the prognosis for PDAC, PHC, and PBTC. Notably, these nomograms were calibrated modestly (c-indexes of 0.690 for PDAC, 0.669 for PHC, and 0.704 for PBTC), presented better accuracy and reliability than the 8 AJCC staging system, and achieved clinical validity.

Conclusions: PHC and PBTC share the differential clinical-pathological characteristics and survival. The nomograms show good performance for predicting prognosis in PHC and PBTC. Therefore, these nomograms hold potential as novel approaches for predicting survival of PHC and PBTC patients after surgery.
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http://dx.doi.org/10.3389/fonc.2021.646082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103839PMC
April 2021

Plasma levels of phosphorylated tau 181 are associated with cerebral metabolic dysfunction in cognitively impaired and amyloid-positive individuals.

Brain Commun 2021 15;3(2):fcab073. Epub 2021 Apr 15.

Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montréal, QC, Canada.

Alzheimer's disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer's disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [F]fluorodeoxyglucose PET in Alzheimer's disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer's Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer's disease, comparatively to PET, MRI and CSF methods.
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http://dx.doi.org/10.1093/braincomms/fcab073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088291PMC
April 2021

Facile production of chlorophyllides using recombinant CrCLH1 and their cytotoxicity towards multidrug resistant breast cancer cell lines.

PLoS One 2021 30;16(4):e0250565. Epub 2021 Apr 30.

Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.

The purity of chlorophylls plays one of the key role for the production of chlorophyllides. We have designed a facile method for chlorophyll purification by twice solvent extraction. Twice extraction causes the loss of chlorophylls, but the purity of total chlorophylls can be enhanced 182%. Then, the purified chlorophylls can be converted to relatively pure chlorophyllides facilely. The results show that higher purity of chlorophyllides could be obtained when purified chlorophylls (ethanol-hexane extract) was used as starting materials than that of crude chlorophylls (ethanol-only extract). In biocompatibility test, the results showed that the prepared chlorophyllides can be applied as biomaterials. When the prepared chlorophyllides were applied to anticancer tests, they were active both in MCF7 and MDA-MB-231 (multidrug resistant breast cancer cells) cell lines. In addition, the results suggested that the prepared chlorophyllides could be a potential candidate of combination therapy with doxorubicin to breast cancers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250565PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087012PMC
April 2021

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.

Mol Neurodegener 2021 04 26;16(1):28. Epub 2021 Apr 26.

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, 6875 Boulevard LaSalle, Montreal, H4H 1R3, Canada.

Background: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [F]BCPP-EF.

Methods: Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [F]BCPP-EF mitochondrial function, [C]PBB3 for tau deposition, and [C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed.

Results: The [F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [F]BCPP-EF SUVR and [C]PBB3 BP (R = 0.2679, p = 0.04), but not [C] PiB SUVR.

Conclusions: Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.
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http://dx.doi.org/10.1186/s13024-021-00448-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074456PMC
April 2021

Plasma pTau181 predicts cortical brain atrophy in aging and Alzheimer's disease.

Alzheimers Res Ther 2021 03 29;13(1):69. Epub 2021 Mar 29.

The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada.

Background: To investigate the association of plasma pTau181, assessed with a new immunoassay, with neurodegeneration of white matter and gray matter cross-sectionally and longitudinally, in aging and Alzheimer's disease.

Methods: Observational data was obtained from the Alzheimer's Disease Neuroimaging Initiative, in which participants underwent plasma assessment and magnetic resonance imaging. Based on their clinical diagnosis, participants were classified as cognitively unimpaired and cognitively impaired. Linear regressions and linear mixed-effect models were used to test the cross-sectional and longitudinal associations between baseline plasma pTau181 and neurodegeneration using voxel-based morphometry.

Results: We observed a negative correlation at baseline between plasma pTau181 and gray matter volume in cognitively unimpaired individuals. In cognitively impaired individuals, we observed a negative association between plasma pTau181 and both gray and white matter volume. In longitudinal analyses conducted in the cognitively unimpaired group, plasma pTau181 was negatively correlated with gray matter volume, starting 36 months after baseline assessments. Finally, in cognitively impaired individuals, plasma pTau181 concentrations were negatively correlated with both gray and white matter volume as early as 12 months after baseline, and neurodegeneration increased in an incremental manner until 48 months.

Conclusions: Higher levels of plasma pTau181 correlate with neurodegeneration and predict further brain atrophy in aging and Alzheimer's disease. Plasma pTau181 may be useful in predicting AD-related neurodegeneration, comparable to positron emission tomography or cerebrospinal fluid assessment with high specificity for AD neurodegeneration.
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http://dx.doi.org/10.1186/s13195-021-00802-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008680PMC
March 2021

[Application of different surface treatment methods in teeth restoration with nano composite resin].

Shanghai Kou Qiang Yi Xue 2020 Dec;29(6):591-595

Department of Stomatology,Haikou Third People's Hospital.Haikou 571100, Hainan Province, China.

Purpose: To investigate the effects of different surface treatments and adhesive self-etch functional monomers on the immediate repair bond strength and integrity of the repaired resin composite interface.

Methods: Ninety-eight resin composite blocks made of a nanohybrid resin composite were randomly divided into seven groups, each with 14 blocks, including positive control group: non-conditioned surface, Group A1: Gluma Comfort Bond, Group A2: Gluma Comfort Bond and sandblasting, Group B1: Tokuyama Bond Force IITM adhesive system, Group B2: Tokuyama Bond Force IITM adhesive system and sandblasting, Group C: polishing, and Group D: sandblasting. Resin composite identical to the substrate was applied and the repaired specimens were subjected to shear bond strength (SBS) testing. Representative samples from all groups received scanning electron microscopy and surface profilometry to determine their mode of failure. The data were processed with SPSS 20.0 software package.

Results: SBS of Group D was significantly higher than that of positive control group (P<0.05). SBS of Group A1, A2, B1 and B2 was significantly higher than that of Group C and D (P<0.05). Comparison of SBS among Group B1, D and A1 showed no significant difference(P>0.05). SBS between Group B2 and positive control group had no significant difference(P>0.05). Except specimens with sandblasting and the use of TBF II system, SBS of positive control group was significantly higher than that of Group A1 and C(P<0.05). The polished specimens had significantly more adhesive failures than those with sandblasted surfaces (P<0.05). Specimens treated with polishing and Gluma Comfort Bond showed significantly more adhesive failures than those treated with polishing and TBF II system (P<0.05). The sandblasted surfaces conditioned with TBF II showed significantly more cohesive failures than those treated with polishing and TBF II (P<0.05). The sandblasted specimens provided significantly more irregular and rougher surface finish than the polishing technique (P<0.05).

Conclusions: Sandblasting of the composite substrate and the use of TBF II adhesive system shows the highest repair bond strength, higher adhesive interfacial failures and fewer cohesive failures; however, it is noteworthy that the composite substrate types yield statistically higher food residue rate, which results in poor oral hygiene maintenance. Therefore, the application of this repair protocol should match up with correct oral health behaviors.
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December 2020

Integrating site-specific peptide reporters and targeted mass spectrometry enables rapid substrate-specific kinase assay at the nanogram cell level.

Anal Chim Acta 2021 Apr 20;1155:338341. Epub 2021 Feb 20.

Molecular Science and Technology Program, Taiwan International Graduate Program, Academia Sinica and National Tsing Hua University, Taiwan; Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan; Department of Chemistry, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 10617, Taiwan. Electronic address:

Dysregulation of phosphorylation-mediated signaling drives the initiation and progression of many diseases. A substrate-specific kinase assay capable of quantifying the altered site-specific phosphorylation of its phenotype-dependent substrates provides better specificity to monitor a disease state. We report a sensitive and rapid substrate-specific kinase assay by integrating site-specific peptide reporter and multiple reaction monitoring (MRM)-MS platform for relative and absolute quantification of substrate-specific kinase activity at the sensitivity of nanomolar kinase and nanogram cell lysate. Using non-small cell lung cancer as a proof-of-concept, three substrate peptides selected from constitutive phosphorylation in tumors (HDGF-S165, RALY-S135, and NRD1-S94) were designed to demonstrate the feasibility. The assay showed good accuracy (<15% nominal deviation) and reproducibility (<15% CV). In PC9 cells, the measured activity for HDGF-S165 was 3.2 ± 0.2 fmol μg min, while RALY-S135 and NRD1-S94 showed 4- and 20-fold higher activity at the sensitivity of 25 ng and 5 ng lysate, respectively, suggesting different endogenous kinases for each substrate peptide. Without the conventional shotgun phosphoproteomics workflow, the overall pipeline from cell lysate to MS data acquisition only takes 3 h. The multiplexed analysis revealed differences in the phenotype-dependent substrate phosphorylation profiles across six NSCLC cell lines and suggested a potential association of HDGF-S165 and NRD1-S94 with TKI resistance. With the ease of design, sensitivity, accuracy, and reproducibility, this approach may offer rapid and sensitive assays for targeted quantification of the multiplexed substrate-specific kinase activity of small amounts of sample.
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http://dx.doi.org/10.1016/j.aca.2021.338341DOI Listing
April 2021

Phenanthridine Derivative Host Heat Shock Cognate 70 Down-Regulators as Porcine Epidemic Diarrhea Virus Inhibitors.

J Nat Prod 2021 04 24;84(4):1175-1184. Epub 2021 Mar 24.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.

Porcine epidemic diarrhea virus (PEDV) has become increasingly problematic around the world, not only for its hazards to livestock but also due to the possibility that it is a zoonotic disease. Although vaccine therapy has made some progress toward PEDV control, additional effective therapeutic strategies against PEDV are needed, such as the development of chemotherapeutic agents. The aim of this work was to identify novel anti-PEDV agents by designing and synthesizing a series of phenanthridine derivatives. Among them, three compounds (compounds , , and ) were identified as potent anti-PEDV agents exhibiting suppression of host cell heat shock cognate 70 (Hsc70) expression. Mechanism studies revealed that host Hsc70 is involved in the replication of PEDV, and its expression can be suppressed by destabilization of the mRNA, resulting in inhibition of PEDV replication. Activity against PEDV in vivo in PEDV-infected piglets suggested that phenanthridine derivatives are the first host-acting potential anti-PEDV agents.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01252DOI Listing
April 2021

Metagenome Sequencing Reveals the Midgut Microbiota Makeup of and Its Possible Relationship With Insecticide Resistance.

Front Microbiol 2021 25;12:625539. Epub 2021 Feb 25.

State Key Laboratory of Pathogen and Biosecurity, Beijing Key Laboratory of Vector Borne and Natural Focus Infectious Disease, Institute of Microbiology and Epidemiology, Beijing, China.

Midgut microbiota can participate in the detoxification and metabolism processes in insects, but there are few reports on the relationship between midgut microbiota and insecticide resistance in mosquitoes. In this study, we performed metagenomic sequencing on a susceptible strain (SS), a field-collected Hainan strain (HN), and a deltamethrin-resistant strain (RR) of to understand the diversity and functions of their midgut microbiota. The results revealed differences in midgut microbiota among the three strains of . At the phylum level, Proteobacteria was the most prominent, accounting for nearly 70% of their midgut microbes. At the genus level, made up the highest proportion. In addition, , , , , , and showed significant differences between strains. At the species level, , sp. 4DZ3-17B2, sp. CNQ329, and some species of and were more abundant in the two resistant strains. Principal component analysis (PCA) showed that the SS strain had significantly different metagenomic functions than the two deltamethrin-resistant strains (HN and RR strain). The HN and RR strains differed from the SS strain in more than 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The analysis of species abundance and functional diversity can provide directions for future studies.
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http://dx.doi.org/10.3389/fmicb.2021.625539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948229PMC
February 2021

A Review of Bacteriochlorophyllides: Chemical Structures and Applications.

Molecules 2021 Feb 27;26(5). Epub 2021 Feb 27.

Department of Biological Science and Technology, College of Medicine, I-Shou University, No.8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan.

Generally, bacteriochlorophyllides were responsible for the photosynthesis in bacteria. Seven types of bacteriochlorophyllides have been disclosed. Bacteriochlorophyllides // could be synthesized from divinyl chlorophyllide . The other bacteriochlorophyllides /// could be synthesized from chlorophyllide . The chemical structure and synthetic route of bacteriochlorophyllides were summarized in this review. Furthermore, the potential applications of bacteriochlorophyllides in photosensitizers, immunosensors, influence on bacteriochlorophyll aggregation, dye-sensitized solar cell, heme synthesis and for light energy harvesting simulation were discussed.
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http://dx.doi.org/10.3390/molecules26051293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957641PMC
February 2021

Surfactant-assisted one-pot sample preparation for label-free single-cell proteomics.

Commun Biol 2021 03 1;4(1):265. Epub 2021 Mar 1.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.

Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for 'all-in-one' one-pot sample preparation. This 'all-in-one' method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.
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http://dx.doi.org/10.1038/s42003-021-01797-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921383PMC
March 2021

A simple, one-pot and ultrasensitive DNA sensor via Exo III-Assisted target recycling and 3D DNA walker cascade amplification.

Anal Chim Acta 2021 Feb 21;1147:15-22. Epub 2020 Dec 21.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang, 110819, China.

Rapid, sensitive, and user-friendly nucleic acid detection is of growing importance in early clinical diagnosis. Here, we construct a simple, one-pot and ultrasensitive DNA sensor via exonuclease III (Exo III)-assisted target recycling amplification (ERA) combined with 3D DNA walker cascade amplification. In the presence of single-stranded DNA target, the ERA process is activated to generate numerous walker strands (WS). Thereafter, Exo III-powered WSs autonomously move along magnetic bead (MB)-based 3D track to release numerous AgNCs into the supernatant as an amplified signal output. This biosensor had a low detection limit of 18 fM and an analytical range of 40 fM to 1 pM. Furthermore, the practical application potential of this biosensor was also confirmed by the spiking experiments of p53 into human serum and urine samples.
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http://dx.doi.org/10.1016/j.aca.2020.12.026DOI Listing
February 2021

The fission yeast Pin1 peptidyl-prolyl isomerase promotes dissociation of Sty1 MAPK from RNA polymerase II and recruits Ssu72 phosphatase to facilitate oxidative stress induced transcription.

Nucleic Acids Res 2021 01;49(2):805-817

Institute of Molecular & Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.

Pin1 is a peptidyl-prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II (Pol II) through interaction with the C-terminal domain (CTD) of Rpb1, the largest subunit of Pol II. We demonstrated that this function is important for cellular response to oxidative stress in the fission yeast Schizosaccharomyces pombe. In response to oxidative stress, the Atf1 transcription factor targets Sty1, the mitogen-activated protein kinase (MAPK), to specific stress-responsive promoters. Anchored Sty1 recruits Pol II through direct association with Rpb1-CTD and phosphorylates the reiterated heptad sequence at Serine 5. Pin1 binds phosphorylated CTD to promote dissociation of Sty1 from it, and directly recruits Ssu72 phosphatase to facilitate dephosphorylation of CTD for transcription elongation. In the absence of Pin1, the association of Sty1-Atf1 with Rpb1 persists on stress-responsive promoters failed to generate transcripts of the corresponding genes effectively. The identified characteristic features of the fission yeast Pin1 are conserved in humans. We demonstrated that elevated Pin1 level in cancer cells might help to sustain survival under oxidative stress generated from their altered metabolic pathways. Together, these results suggest a conserved function of Pin1 in cellular response to oxidative stress among eukaryotic cells that might have clinical implication.
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http://dx.doi.org/10.1093/nar/gkaa1243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826279PMC
January 2021

Trends in the Immunomodulatory Effects of : Total Extracts, Polysaccharides and Cordycepin.

Front Pharmacol 2020 30;11:575704. Epub 2020 Nov 30.

Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.

() is a fungus with a long history of widespread use in folk medicine, and its biological and medicinal functions are well studied. A crucial pharmacological effect of is immunomodulation. In this review, we catalog the immunomodulatory effects of different extracts of , namely total extracts, polysaccharides and cordycepin Total extracts obtained using water or 50% ethyl alcohol and polysaccharides from were discovered to tend to promote type 1 immunity, whereas total extracts obtained using 70-80% ethyl alcohol and cordycepin from were more likely to promote type 2 immunity. This article is the first to classify the immunomodulatory effects of different extracts of . In addition, we discovered a relationship between different segments or extracts and differing types of immunity. This review can provide the readers a comprehensive understanding on the immunomodulatory effects of the precious folk medicine and guidance on its use for both health people and those with an immunodeficiency.
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http://dx.doi.org/10.3389/fphar.2020.575704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735063PMC
November 2020

Carbon nitride nanoparticles as ultrasensitive fluorescent probes for the detection of α-glucosidase activity and inhibitor screening.

Analyst 2021 Feb 9;146(3):1016-1022. Epub 2020 Dec 9.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang 110819, China.

In recent years, α-glucosidase inhibitors (AGIs) have played a significant role in the treatment of type II diabetes (T2D), so it is necessary to develop a reliable and sensitive method to find new AGIs. Herein, we establish a novel method based on fluorescent carbon nitride nanoparticles (CNNPs) for the sensitive detection of the activity of α-glucosidase (α-glu) and the screening of its inhibitors. A CNNP-based fluorescent probe is synthesized from green raw materials, urea and lysine, by a one-pot method. In the presence of α-glu, the substrate 4-nitrophenyl-α-d-glucopyranoside (pNPG) is hydrolyzed to generate 4-nitrophenol (pNP), leading to the fluorescence (FL) quenching of CNNPs due to the inner filter effect (IFE). On the other hand, the activity of α-glu is inhibited after the addition of AGIs, which turns on the FL of CNNPs. In this way, the detection of α-glu activity and the screening of AGIs are achieved. The linear range is 1.25-10.00 U L with a limit of detection as low as 0.17 U L and the IC values of two typical inhibitors (gallic acid and acarbose) are 813 μM and 465 μM, respectively. The CNNP probe is further applied for the determination of α-glu activity in human serum samples with satisfactory results.
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http://dx.doi.org/10.1039/d0an02079fDOI Listing
February 2021

Site-Selective Alkenylation of Unactivated C(sp )-H Bonds Mediated by Compact Sulfate Radical.

Angew Chem Int Ed Engl 2021 Feb 14;60(7):3545-3550. Epub 2020 Dec 14.

Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka, 599-8531, Japan.

A broad variety of unactivated acyclic and alicyclic substrates cleanly undergo site-selective alkenylation of unactivated C(sp )-H bonds with 1,2-bis(phenylsulfonyl)ethene in the presence of persulfate. This simple transformation furnishes (E)-2-alkylvinylphenylsulfones in up to 88 % yield. In contrast with the previously reported decatungstate protocol, the current method is applicable to alkenylation of sterically hindered C-H bonds. This important advantage significantly broadens the substrate scope, and is attributed to the compact size of the sulfate radical employed in the C-H activation and cleavage.
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http://dx.doi.org/10.1002/anie.202011992DOI Listing
February 2021

Sexually Inactive Status in Women With Pelvic Organ Prolapse Before Colpocleisis and Postoperative Satisfaction and Regret Rate.

Female Pelvic Med Reconstr Surg 2020 Oct 26. Epub 2020 Oct 26.

From the Peking University Third Hospital, Beijing.

Purpose: The aim of the study was to investigate the sexually inactive status of patients with pelvic organ prolapse before colpocleisis and postoperative satisfaction and regret rate.

Methods: A retrospective study of patients with pelvic organ prolapse who underwent colpocleisis was conducted in our hospital from January 2007 to April 2019. Records were reviewed before surgery for general clinical characteristics, duration, and reasons for being sexually inactive. Follow-up was conducted by telephone about patient satisfaction, Patient Global Impression of Improvement score, and regret rate after surgery.

Results: The mean age of the 247 patients was 73.8 ± 5.58 years. A total of 76.9% (190/247) described the duration of being sexually inactive, and the mean time was 12.6 ± 8.69 years. The 247 patients gave the following reasons for being sexually inactive: 52.2% (129/247) were widowed and 37.2% (92/247) reported the physical health factors of their spouses or sexual partners. The first male factor was nervous system disease (37.0%, 34/92). A total of 5.3% (13/247) were patient-related factors and 5.3% (13/247) were factors of both the male and female. A total of 195 patients underwent follow-up, the rate was 78.9% (195/247), and the follow-up time was 39.7 ± 37.5 (2-140) months. A total of 98.5% (192/195) of patients were very satisfied. A total of 98.9% (193/195) of patients were very much improved or improved in Patient Global Impression of Improvement score. A total of 1.02% (2/195) of patients regretted having colpocleisis nearly 2 years later.

Conclusions: The main reason for being sexually inactive was having been widowed. Colpocleisis was associated with high satisfaction rates and low regret rate.
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http://dx.doi.org/10.1097/SPV.0000000000000974DOI Listing
October 2020

M13 phage-based nanoprobe for SERS detection and inactivation of Staphylococcus aureus.

Talanta 2021 Jan 15;221:121668. Epub 2020 Sep 15.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang, 110819, China. Electronic address:

Rapid and sensitive diagnosis of bacterial infections at early stage is of great significance for food safety monitoring as well as clinical treatment. Herein, we construct a surface-enhanced Raman scattering (SERS) nanoprobe based on M13 phages for the selective detection and inactivation of Staphylococcus aureus (S. aureus). M13 phage with specific S. aureus-binding heptapeptide displayed on the N-terminal of pIII protein is selected from phage display peptide library. The S. aureus-specific SERS probe is thus constructed by in situ growth of gold nanoparticles (AuNPs) on M13 phage surface, followed by modification with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) as SERS active molecule. Upon the addition of this SERS probe, M13 phage selectively binds with S. aureus to induce anchoring of AuNPs on S. aureus surface, and the SERS probe-labeled S. aureus cells are collected by centrifugation for SERS detection. For the quantification of S. aureus, a linear range of 10-10 cfu mL is achieved in aqueous medium. It is further demonstrated by spiking recovery in soft drinks. Furthermore, this SERS probe exhibits bactericidal capabilities towards S. aureus, which shows promising potential to serve as a multifunctional platform for simultaneous detection and inactivation of S. aureus.
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http://dx.doi.org/10.1016/j.talanta.2020.121668DOI Listing
January 2021

Proteomic Analysis of Exosomes for Discovery of Protein Biomarkers for Prostate and Bladder Cancer.

Cancers (Basel) 2020 Aug 19;12(9). Epub 2020 Aug 19.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.

Extracellular vesicles (EVs) are released by nearly all cell types as part of normal cell physiology, transporting biological cargo, including nucleic acids and proteins, across the cell membrane. In pathological states such as cancer, EV-derived cargo may mirror the altered state of the cell of origin. Exosomes are the smaller, 50-150 nanometer-sized EVs released from fusion of multivesicular endosomes with the plasma membrane. Exosomes play important roles in cell-cell communication and participate in multiple cancer processes, including invasion and metastasis. Therefore, proteomic analysis of exosomes is a promising approach to discover potential cancer biomarkers, even though it is still at an early stage. Herein, we critically review the advances in exosome isolation methods and their compatibility with mass spectrometry (MS)-based proteomic analysis, as well as studies of exosomes in pathogenesis and progression of prostate and bladder cancer, two common urologic cancers whose incidence rates continue to rise annually. As urological tumors, both urine and blood samples are feasible for noninvasive or minimally invasive analysis. A better understanding of the biological cargo and functions of exosomes via high-throughput proteomics will help provide new insights into complex alterations in cancer and provide potential therapeutic targets and personalized treatment for patients.
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http://dx.doi.org/10.3390/cancers12092335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564640PMC
August 2020

Group C Streptococcus dysgalactiae infection in fish.

J Fish Dis 2020 Sep 13;43(9):963-970. Epub 2020 Jul 13.

Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan.

Streptococcus dysgalactiae subsp. dysgalactiae (GCSD) is a Gram-positive, facultative anaerobic bacterium and mostly non-β-haemolytic with Lancefield group C antigen. GCSD infection has been identified in various vertebrates. From 2002 to the present, GCSD infection of fish has been reported to cause severe economic losses in aquaculture farms around the world. Moreover, GCSD isolates from teleosts have been identified in patients with ascending upper limb cellulitis. Therefore, the economic and clinical significance of GCSD has increased in aquaculture, livestock and human health. Many studies have been presented, from the first report of isolated GCSD in fish, to the pathogenesis, characterization, immune responses and vaccine development. In this review, we present the current knowledge of GCSD in teleosts.
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http://dx.doi.org/10.1111/jfd.13211DOI Listing
September 2020

Three-Dimensional DNA Nanomachine Biosensor by Integrating DNA Walker and Rolling Machine Cascade Amplification for Ultrasensitive Detection of Cancer-Related Gene.

Anal Chem 2020 08 29;92(16):11111-11118. Epub 2020 Jul 29.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang 110819, China.

Stochastic DNA walkers capable of traversing on three-dimensional (3D) tracks have received great deal of attention. However, DNA walker-based biosensors exhibit limited amplification efficiency because of their slow walking kinetics and low processivity. Herein, by taking advantage of the high processivity of a DNA rolling machine, a sensitive ratiometric DNA nanomachine biosensor is designed. The biosensor is constructed with hairpin-loaded Au nanoparticles (NPs) ([email protected]) as a DNA walker and AgNCs-decorated magnetic NPs ([email protected]) as a DNA rolling machine. In the presence of target DNA, exonuclease III (Exo III)-powered DNA walker is activated to accomplish first-stage amplification via a burnt-bridge mechanism, generating a great deal of toehold-loaded AuNPs ([email protected]) to hybridize with magnetic nanoparticles loaded with silver-nanoclusters-labeled DNA ([email protected]) with the assistance of Exo III. These trigger rapid rolling of AuNPs on the [email protected] surface and release free AgNCs, converting the biological signal into a mass spectrometric signal ratio (Ag/Au) with detection by ICP-MS. A linear range of 0.5-500 fmol L is achieved with a detection limit of 119 amol L for the gene. The practical applicability of the biosensor has been demonstrated in the accurate assay of the gene in the human blood.
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http://dx.doi.org/10.1021/acs.analchem.0c01074DOI Listing
August 2020

Long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse.

Int Urogynecol J 2021 Apr 29;32(4):879-884. Epub 2020 Jun 29.

Peking University Third Hospital, No. 49 North Garden Road, Beijing, 100191, Haidian district, China.

Introduction And Hypothesis: The objective was to investigate the long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse.

Methods: This was a retrospective study of patients who underwent Le Fort colpocleisis from January 2007 to August 2018 in our hospital. Follow-up was conducted via outpatient visits or the telephone. Records were reviewed for anatomical recurrence, complications, urinary and intestinal symptoms post-operation, reoperation rate, patient satisfaction, Patient Global Impression of Improvement (PGI-I) score, regret rate etc. RESULTS: A total of 208 patients underwent follow-up. The follow-up time was 60.7 ± 34.18 (12-140) months. There were no intraoperative complications. Postoperative urinary retention occurred in 3.8% of patients (8 out of 208). There was no anatomical recurrence. New or more severe urinary symptoms occurred in 8.7% of patients (18 out of 208); new or more severe intestinal symptoms occurred in 1.9% of patients (4 out of 208). The reoperation rate was 1.44% (3 out of 208). Three cases of reoperation occurred for the following reasons: a case of severe stress urinary incontinence, a case of abscess in the vaginal septum, and a case of uterine malignancy after 2 years of colpocleisis. Patient satisfaction was as follows: 98.6% (205 out of 208) of patients were very satisfied. The PGI-I score was very much improved or improved in 99.5% (207 out of 208) of patients. A total of 0.96% (2 out of 208) of patients regretted undergoing colpocleisis.

Conclusions: The long-term follow-up results showed that Le Fort colpocleisis was a safe and effective surgical procedure associated with high satisfaction. There was a very low regret rate, but the procedure should be taken seriously.
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http://dx.doi.org/10.1007/s00192-020-04380-8DOI Listing
April 2021

Hyperbranched Poly(amido amine) Entrapped Tetraphenylethene as a Fluorescence Probe for Sequential Quadruple-Target Detection and Its Potential as a Chemical Logic Gate.

Anal Chem 2020 07 1;92(14):9755-9763. Epub 2020 Jul 1.

Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin 300354, People's Republic of China.

Fluorescence sensors exhibit great potential as molecular logic gates to perform computation on a nanometer scale. For achieving the more complex artificial intelligence activities, developing complex logic gates using multitarget sensing systems with multi-input characteristics is highly desirable. Herein, a water-soluble quadruple-target fluorescence sensor that embeds a small amount (4.1 wt %) of tetraphenylethene (TPE) units into hyperbranched poly(amido amine) (TPE-HPA) has been designed. The nonfluorescent TPE-HPA could experience the fluorescence "off-on-off-on-off" by sequential addition of sodium hexametaphosphate (SHMP), Fe, ascorbic acid (AA), and HO. The as-prepared quadruple-target sensor showed good sensitivity and selectivity to SHMP, Fe, AA, and HO, and the limit of detection values were 29 nM, 20 nM, 0.66 μM, and 0.78 μM, respectively. On the basis of the multitarget sensing nature of TPE-HPA, chemical or electrochemical-induced logic gates were constructed, including YES, NOT, OR, NOR, NAND, INHIBIT, IMP, and higher logic systems.
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http://dx.doi.org/10.1021/acs.analchem.0c01155DOI Listing
July 2020

Detection of Head and Neck Cancer Based on Longitudinal Changes in Serum Protein Abundance.

Cancer Epidemiol Biomarkers Prev 2020 08 12;29(8):1665-1672. Epub 2020 Jun 12.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington.

Background: Approximately 85% of the U.S. military active duty population is male and less than 50 years of age, with elevated levels of known risk factors for oropharyngeal squamous cell carcinoma (OPSCC), including smoking, excessive use of alcohol, and greater numbers of sexual partners, and elevated prevalence of human papilloma virus (HPV). Given the recent rise in incidence of OPSCC related to the HPV, the Department of Defense Serum Repository provides an unparalleled resource for longitudinal studies of OPSCC in the military for the identification of early detection biomarkers.

Methods: We identified 175 patients diagnosed with OPSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature.

Results: Using a Random Forest machine learning approach, we derived a 13-protein signature that distinguishes cases versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The AUC for the derived Random Forest classifier was 0.90.

Conclusions: This 13-protein classifier is highly promising for detection of OPSCC prior to overt symptoms.

Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0192DOI Listing
August 2020

Aphananoid A is an Anti-Inflammatory Limonoid with a New 5/6/5 Fused Ring Featuring a C Carbon Skeleton from .

J Org Chem 2020 07 17;85(13):8597-8602. Epub 2020 Jun 17.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

Aphananoid A, a limonoid which features a rare C appendage and new 5/6/5 fused-ring framework, was obtained from . The planar structure as well as the absolute configuration was identified based on extensive spectroscopic analysis and electronic circular dichroism calculations. The biogenetic pathway of aphananoid A was also speculated, which arises from the triterpene by the 3,4--7,8--6,8 -7,30- key pattern. In addition, bioassays indicated that aphananoid A inhibited NO production in the RAW264.7 cell line (46.80 ± 1.93%).
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http://dx.doi.org/10.1021/acs.joc.0c00922DOI Listing
July 2020

Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression.

Cancers (Basel) 2020 May 17;12(5). Epub 2020 May 17.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.
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http://dx.doi.org/10.3390/cancers12051268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281161PMC
May 2020

Risk of ankylosing spondylitis following human papillomavirus infection: A nationwide, population-based, cohort study.

J Autoimmun 2020 09 13;113:102482. Epub 2020 May 13.

School of Health Policy and Management, Chung Shan Medical University, Taichung, Taiwan. Electronic address:

Objective: To assess the incidence rate and risk of ankylosing spondylitis (AS) in patients with previous human papillomavirus (HPV) infection compared with those without HPV infection.

Methods: All patients with HPV infection (n = 66,314) in the NHIRD (2003-2013) were individually matched with up to four control subjects without HPV infection by age and sex (n = 265,256). All of the patients were tracked until an AS event was noted. Chi-square test was used to analyze the distribution of sociodemographic characteristics in the HPV cohort and non-HPV cohort. Cox proportional hazards regression was used to calculate the HRs for the development of AS, adjusting for age, sex, urbanization, length of hospital stay, medications, and comorbidities adjustment. The Kaplan-Meier method was used to plot the cumulative incidence curves.

Results: The HPV cohort had a 1.329 (95% C.I. = 1.138-1.552) times higher risk of AS than that of the non-HPV cohort after adjusting for sex, age, urbanization, length of hospital stay, comorbidities, and medications. Additionally, we applied propensity score weighting to reconfirm the accuracy of our analysis, and the results showed a 1.348 (95% C.I. = 1.153-1.575) times greater risk of AS in the HPV cohort compared with the non-HPV cohort. The cumulative incidence curves plotted by the Kaplan-Meier method revealed that after 120 follow-up months, the HPV cohort displayed a higher cumulative incidence of AS than that of the non-HPV cohort. (Log-rank test p < 0.0001).

Conclusions: Patients with HPV infection had a higher risk of developing AS compared with non-HPV patients.
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http://dx.doi.org/10.1016/j.jaut.2020.102482DOI Listing
September 2020
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