Publications by authors named "Ya-Ting Chen"

83 Publications

Impact of the COVID-19 pandemic on adolescent vaccinations: projected time to reverse deficits in routine adolescent vaccination in the United States.

Curr Med Res Opin 2021 Sep 20. Epub 2021 Sep 20.

Merck & Co, Inc, Kenilworth, NJ, USA.

Objective: The COVID-19 pandemic has led to significant reductions in the administration of routinely recommended vaccines among adolescents in the US including tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal (ACWY); and human papillomavirus (HPV) vaccines. The extent to which these deficits could persist in 2021 and beyond is unclear. To address this knowledge gap, this study estimated the cumulative deficits of routine vaccine doses among US adolescents during the COVID-19 pandemic, and estimated the time and effort needed to recover from those deficits. : Monthly reductions in Tdap, meningococcal, and HPV doses administered to US adolescents during the COVID-19 pandemic were quantified using MarketScan Commercial Claims and Encounters data. The time and effort required to reverse the vaccination deficit under various catch-up scenarios were estimated. : Annual doses administered of Tdap, meningococcus, and HPV vaccines decreased by 21.2%, 20.8%, and 24.0%, respectively, in 2020 compared to 2019. For 2021, the reduction in doses administered is projected to be 6%-21% compared to 2019 under different scenarios. The deficit of missed doses is expected to be cleared between winter 2023 and fall 2031. : Administration rates of routine vaccines decreased significantly among US adolescents during COVID-19. Reversing these deficits to mitigate long-term health and economic consequences will require a sustained increase in vaccination rates over multiple years.
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http://dx.doi.org/10.1080/03007995.2021.1981842DOI Listing
September 2021

Evaluation of Chemical Compositions, Antioxidant Capacity and Intracellular Antioxidant Action in Fish Bone Fermented with .

Molecules 2021 Aug 31;26(17). Epub 2021 Aug 31.

Department of Chemical and Materials Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 80778, Taiwan.

Fish bones (FBs) are aquatic by-products that are sources of antioxidant-active peptides, calcium dietary supplements, and biomedical materials. Usually, fermentation of these by-products via microorganisms brings desirable changes, enhancing their value. This study investigates the value addition of FB when fermented with (MP) for different time intervals, such as 3 days (F3) and 6 days (F6). The results indicate that the soluble protein, peptide, amino acid and total phenol content, as well as the antioxidant capacity (DPPH, ABTS radical scavenging activity, and relative reducing power), of F3 and F6 were significantly increased after fermentation. Furthermore, the ROS contents of F3 and F6 were reduced to a greater extent than that of hydrogen peroxide (HO) in Clone-9 cells. The MMP integrity, as well as the SOD, CAT, and GPx activity, of F3 and F6 were also increased significantly compared to the HO in Clone-9 cells. Notably, F3 and F6 displayed significant reductions in ROS content, as well as elevate, SOD activity and MMP integrity in Clone-9 cells, when compared with the native FB. These results indicate that the FBs fermented with MP for 3 days (F3), and 6 days (F6) have antioxidant capacity, with possible applications as natural food supplements.
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http://dx.doi.org/10.3390/molecules26175288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434028PMC
August 2021

Genetic characterization of a novel HIV-1 second-generation recombinant form originating from CRF86_BC and a unique recombinant form in Yunnan, China.

AIDS Res Hum Retroviruses 2021 Aug 31. Epub 2021 Aug 31.

Gannan Medical University, 74554, Department of Pathogenic Biology, School of Basic Medical Sciences, 1 Hexie Avenue, Ganzhou, Jiangxi, China, 341000;

Yunnan is the first place where HIV-1 became prevalent in China, and it is also the place with the most complicated HIV-1 genetic diversity in China. On October 23, 2019, a patient newly diagnosed with acquired immunodeficiency syndrome from a hospital in Baosan, Yunnan, was recruited for genetic analysis. Near full-length genome of HIV-1 was amplified from the plasma sample. Phylogenetic analysis revealed that this sequence (BS6F24) has a close relationship with CRF86_BC and a unique recombinant form (KY406739), which was formed by recombination of subtypes B and C. Bootscan analysis confirmed that the first part (HXB2:1022-5832) and last part (HXB2:5833-9120) genomes of BS6F24 had the same recombinant structures as KY406739 and CRF86_BC, respectively. A second-generation recombinant form that originated from CRF86_BC and a unique recombinant form were reported for the first time. This indicates the need for continuous monitoring of the genetic diversity of HIV-1 in Yunnan, China.
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http://dx.doi.org/10.1089/AID.2021.0121DOI Listing
August 2021

The Anti-Obesity Effects of Lemon Fermented Products in 3T3-L1 Preadipocytes and in a Rat Model with High-Calorie Diet-Induced Obesity.

Nutrients 2021 Aug 16;13(8). Epub 2021 Aug 16.

Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan.

Lemon () has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon fermented product (LFP) which is lemon fermented with OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3-L1 adipocytes is examined using a Wistar rat model fed a high-fat diet to verify the anti-obesity efficacy and mechanism of LFP. Here, it was observed that LFP reduced cell proliferation and inhibited the lipid accumulation (8.3%) of 3T3-L1 adipocytes. Additionally, LFP reduced body weight (9.7%) and fat tissue weight (25.7%) of rats; reduced serum TG (17.0%), FFA (17.9%), glucose (29.3%) and ketone body (6.8%); and increased serum HDL-C (17.6%) and lipase activity (17.8%). LFP regulated the mRNA expression of genes related to lipid metabolism (PPARγ, C/EBPα, SREBP-1c, HSL, ATGL, FAS, and AMPK). Therefore, LFP reduces body weight and lipid accumulation by regulating the mRNA expression of genes related to lipid metabolism. Overall, our results implicate LFP as a potential dietary supplement for the prevention of obesity.
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http://dx.doi.org/10.3390/nu13082809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398352PMC
August 2021

Distribution characteristics of drug resistance mutations of HIV CRF01_AE, CRF07_BC and CRF08_BC from patients under ART in Ganzhou, China.

J Antimicrob Chemother 2021 Aug 17. Epub 2021 Aug 17.

Department of Pathogenic Biology, School of Basic Medical Sciences, Gannan Medical University, Ganzhou, China.

Background: Drug resistance mutation (DRM)-associated virological failure has become a critical issue for ART and the elimination of HIV.

Objectives: To investigate the distribution characteristics of DRMs of HIV CRF01_AE, CRF07_BC and CRF08_BC, the predominant subtypes in China.

Methods: Patients receiving ART up to 31 August 2020 in Ganzhou in China were recruited. Full-length sequences of the HIV pol gene were amplified from patients with virological failure. DRMs and antiretroviral susceptibility were explored using the Stanford University HIV Drug Resistance Database HIVdb Program.

Results: Overall, 279 of 2204 patients under ART were found to have virological failure. Nine HIV subtypes were identified among 211 sequences that were amplified successfully and CRF08_BC (37.0%), CRF01_AE (26.1%) and CRF07_BC (25.6%) were the most prevalent, with mutation frequencies of 44.9% (35/78), 52.7% (29/55) and 35.2% (19/54), respectively. The most common DRMs of these three subtypes were K103N and M184V, while the mutation frequencies of M41L, D67N, K70R, K101E, V106M, Y181C, K219E, H221Y and N348I were obviously different among subtypes. The resistance levels and frequencies for antiretroviral drugs for these three subtypes were similar and resistances to nevirapine, efavirenz, lamivudine and emtricitabine were the most frequently observed. Compared with CRF01_AE and CRF07_BC, CRF08_BC had higher proportions of DRMs for NRTIs and lower frequencies of resistance to NRTIs and NNRTIs.

Conclusions: The distribution characteristics of DRMs of HIV CRF01_AE, CRF07_BC and CRF08_BC were inconsistent and should be considered when selecting antiretroviral strategies, developing new drugs and controlling HIV strains containing DRMs.
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http://dx.doi.org/10.1093/jac/dkab296DOI Listing
August 2021

Effect of polyethylene microplastics on oxidative stress and histopathology damages in Litopenaeus vannamei.

Environ Pollut 2021 Jul 17;288:117800. Epub 2021 Jul 17.

Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, 81157, Taiwan. Electronic address:

There has been a significant increase in the microplastic (MP) polluting the ocean in recent time which is regarded as toxic for living organisms. In this study, Fluorescent red polyethylene microspheres (FRPE) were administered intramuscularly to Litopenaeus vannamei juveniles at the concentration of 0.1, 0.2, 0.5 and 1.0 μg (g shrimp), and the survival rate was recorded. Analysis of the hepatopancreas for antioxidant enzyme activity and gene expression were done after seven days. Further tissue morphology and accumulation of FRPE was analysed. The results showed that FRPE at 0.5 and 1.0 μg (g shrimp) reduce the survival rate of L. vannamei. FRPE at 0.5 and 1.0 μg (g shrimp) reduced superoxide dismutase (SOD) activity; FRPE at different concentrations reduced catalase (CAT) activity; FRPE at 0.2, 0.5 and 1.0 μg (g shrimp) increased the lipid peroxide thiobarbituric acid (TBARS) content. FRPE at 0.1, 0.2, and 0.5 μg (g shrimp) significantly affect the performance of SOD and CAT genes; FRPE at 0.2 and 0.5 μg (g shrimp) significantly improves GPx gene performance; FRPE at 1.0 μg (g shrimp) significantly reduced the expression of GPx genes. Analysis of tissue morphology shows that FRPE cause muscle, midgut gland, and hepatopancreas, and gill damage at different concentrations. In the results of accumulation of microplastic, FRPE accumulated in gill tissue at 0.2 and 0.5 μg (g shrimp); FRPE accumulated in gill, muscle and hepatopancreas tissue at 1.0 μg (g shrimp). Based on the above results, FRPE at 0.5 and 1.0 μg (g shrimp) can regulate the antioxidant enzymes of L. vannamei, increase lipid peroxide content, cause tissue damage by accumulating in the tissues. The rate of survival decreased in L. vannamei, and the impact of FRPE at 1.0 μg (g shrimp) was significant.
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http://dx.doi.org/10.1016/j.envpol.2021.117800DOI Listing
July 2021

Distal Gracilis Tear in an Equestrian: A Case Report.

Am J Phys Med Rehabil 2021 Jul 27. Epub 2021 Jul 27.

Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA.

Abstract: A 61-year-old female equestrian presented after two weeks of left medial thigh pain which developed suddenly while exiting a car. She denied any history of recent trauma or falls. On examination she was found to have tenderness at the left distal medial thigh with a palpable region of decreased tissue volume at the gracilis myotendinous junction. Point-of-care ultrasound and MRI confirmed a high-grade partial thickness tear of the left distal gracilis at the myotendinous junction, as well as pes anserine bursal distention. She received physical therapy and underwent a one-time ultrasound-guided corticosteroid injection to the left pes anserine bursa. At follow-up, her symptoms had significantly improved, and she had returned to horseback riding after 12 weeks. Isolated gracilis myotendinous tear is a rare condition and this is a unique case with an atypical mechanism of injury as gracilis injuries have only been reported during vigorous exercise-related activities rather than transitional movements. This case illustrates the potential increased risk of distal gracilis injury after repetitive corticosteroid injections (genicular nerve blocks and radiofrequency lesioning) in a patient who was also likely predisposed to gracilis microtrauma due to her equestrian activities. Gracilis injury should be considered in the differential diagnosis of distal medial thigh pain, especially in cases with similar interventional and recreational profiles.
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http://dx.doi.org/10.1097/PHM.0000000000001854DOI Listing
July 2021

Deciphering Symbiotic Interactions of " Aenigmarchaeota" with Inferred Horizontal Gene Transfers and Co-occurrence Networks.

mSystems 2021 Aug 27;6(4):e0060621. Epub 2021 Jul 27.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.

" Aenigmarchaeota" (" Aenigmarchaeota") represents one of the earliest proposed evolutionary branches within the , , , , and (DPANN) superphylum. However, their ecological roles and potential host-symbiont interactions are still poorly understood. Here, eight metagenome-assembled genomes (MAGs) were reconstructed from hot spring ecosystems, and further in-depth comparative and evolutionary genomic analyses were conducted on these MAGs and other genomes downloaded from public databases. Although with limited metabolic capacities, we reported that " Aenigmarchaeota" in thermal environments harbor more genes related to carbohydrate metabolism than " Aenigmarchaeota" in nonthermal environments. Evolutionary analyses suggested that members from the , , , and (TACK) superphylum and contribute substantially to the niche expansion of " Aenigmarchaeota" via horizontal gene transfer (HGT), especially genes related to virus defense and stress responses. Based on co-occurrence network results and recent genetic exchanges among community members, we conjectured that " Aenigmarchaeota" may be symbionts associated with one MAG affiliated with the genus , though host specificity might be wide and variable across different " Aenigmarchaeota" organisms. This study provides significant insight into possible DPANN-host interactions and ecological roles of " Aenigmarchaeota." Recent advances in sequencing technology promoted the blowout discovery of super tiny microbes in the , , , , and (DPANN) superphylum. However, the unculturable properties of the majority of microbes impeded our investigation of their behavior and symbiotic lifestyle in the corresponding community. By integrating horizontal gene transfer (HGT) detection and co-occurrence network analysis on " Aenigmarchaeota" (" Aenigmarchaeota"), we made one of the first attempts to infer their putative interaction partners and further decipher the potential functional and genetic interactions between the symbionts. We revealed that HGTs contributed by members from the , , , and (TACK) superphylum and conferred " Aenigmarchaeota" with the ability to survive under different environmental stresses, such as virus infection, high temperature, and oxidative stress. This study demonstrates that the interaction partners might be inferable by applying informatics analyses on metagenomic sequencing data.
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http://dx.doi.org/10.1128/mSystems.00606-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407114PMC
August 2021

Comparative Genomics Reveals Thermal Adaptation and a High Metabolic Diversity in " Bathyarchaeia".

mSystems 2021 Aug 20;6(4):e0025221. Epub 2021 Jul 20.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.

" Bathyarchaeia" is a phylogenetically diverse and widely distributed lineage often in high abundance in anoxic submarine sediments; however, their evolution and ecological roles in terrestrial geothermal habitats are poorly understood. In the present study, 35 . Bathyarchaeia metagenome-assembled genomes (MAGs) were recovered from hot spring sediments in Tibet and Yunnan, China. Phylogenetic analysis revealed all MAGs of . Bathyarchaeia can be classified into 7 orders and 15 families. Among them, 4 families have been first discovered in the present study, significantly expanding the known diversity of . Bathyarchaeia. Comparative genomics demonstrated . Bathyarchaeia MAGs from thermal habitats to encode a large variety of genes related to carbohydrate degradation, which are likely a metabolic adaptation of these organisms to a lifestyle at high temperatures. At least two families are potential methanogens/alkanotrophs, indicating a potential for the catalysis of short-chain hydrocarbons. Three MAGs from Family-7.3 are identified as alkanotrophs due to the detection of an Mcr complex. Family-2 contains the largest number of genes relevant to alkyl-CoM transformation, indicating the potential for methylotrophic methanogenesis, although their evolutionary history suggests the ancestor of . Bathyarchaeia was unable to metabolize alkanes. Subsequent lineages have acquired the ability via horizontal gene transfer. Overall, our study significantly expands our knowledge and understanding of the metabolic capabilities, habitat adaptations, and evolution of . Bathyarchaeia in thermal environments. . Bathyarchaeia MAGs from terrestrial hot spring habitats are poorly revealed, though they have been studied extensively in marine ecosystems. In this study, we uncovered the metabolic capabilities and ecological role of . Bathyarchaeia in hot springs and give a comprehensive comparative analysis between thermal and nonthermal habitats to reveal the thermal adaptability of . Bathyarchaeia. Also, we attempt to determine the evolutionary history of methane/alkane metabolism in . Bathyarchaeia, since it appears to be the first archaea beyond which contains the genes. The reclassification of . Bathyarchaeia and significant genomic differences among different lineages largely expand our knowledge on these cosmopolitan archaea, which will be beneficial in guiding the future studies.
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http://dx.doi.org/10.1128/mSystems.00252-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407382PMC
August 2021

Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass.

Ann Transl Med 2021 May;9(9):786

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Current diagnostic strategies for acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) are nonspecific and limited. Previously, we demonstrated that circulating microparticles (MPs) in patients with valve heart disease (VHD) and congenital heart diseases (CHD) induce endothelial dysfunction and neutrophil chemotaxis, which may result in kidney injury. We also found that circulating MPs increase after cardiac surgery with CPB and are related to cardiac function. However, the relationship between circulating MPs and AKI after CPB is unknown.

Methods: Eighty-five patients undergoing cardiac surgery with CPB were enrolled. Patients were divided into AKI and non-AKI groups based on the serum creatinine levels at 12 h and 3 d post-CPB. Circulating MPs were isolated from plasma, and their levels including its subtypes were detected by flow cytometer. Independent risk factors for the CPB-associated AKI (CPB-AKI) were determined by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to measure the prognostic potential of CPB-AKI.

Results: The morbidity of AKI at 12 h and 3 d after cardiac surgery with CPB was 40% and 31.76%, respectively. The concentrations of total MPs and platelet-derived MPs (PMP) remained unchanged at 12 h and then increased at 3 d post-CPB, while that of endothelial-derived MPs (EMP) increased at both time points. In patients with AKI, PMP and EMP were elevated compared with the patients without AKI. However, no significant change was detected on monocyte-derived MPs (MMP) at 12 h and 3 d post-CPB. The logistic regression analysis showed that EMP was the independent risk factor for AKI both at 12 h and 3 d post-CPB. The area under ROC for the concentrations of EMP at 12 h and 3 d post-CPB was 0.86 and 0.91, with the specificity up to 0.88 and 0.91, respectively.

Conclusions: Circulating EMP may serve as a potential biomarker of AKI after cardiac surgery with CPB.
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http://dx.doi.org/10.21037/atm-20-7828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246187PMC
May 2021

Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by increasing tetrahydrobiopterin via regulation of GTP-cyclohydrolase 1 and reducing uncoupled endothelial nitric oxide synthase activity.

Atherosclerosis 2021 07 31;328:83-91. Epub 2021 May 31.

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, PR China; Guangdong Provincial Key Laboratory of Brain Function and Disease,Guangzhou, 510080, PR China. Electronic address:

Background And Aims: The apolipoprotein A-I mimetic peptide D-4F, among its anti-atherosclerotic effects, improves vasodilation through mechanisms not fully elucidated yet.

Methods: Low-density lipoprotein (LDL) receptor null (LDLr) mice were fed Western diet with or without D-4F. We then measured atherosclerotic lesion formation, endothelial nitric oxide synthase (eNOS) phosphorylation and its association with heat shock protein 90 (HSP90), nitric oxide (NO) and superoxide anion (O) production, and tetrahydrobiopterin (BH4) and GTP-cyclohydrolase 1 (GCH-1) concentration in the aorta. Human umbilical vein endothelial cells (HUVECs) and aortas were treated with oxidized LDL (oxLDL) with or without D-4F; subsequently, BH4 and GCH-1 concentration, NO and O production, eNOS association with HSP90, and endothelium-dependent vasodilation were measured.

Results: Unexpectedly, eNOS phosphorylation, eNOS-HSP90 association, and O production were increased, whereas BH4 and GCH-1 concentration and NO production were reduced in atherosclerosis. D-4F significantly inhibited atherosclerosis, eNOS phosphorylation, eNOS-HSP90 association, and O generation but increased NO production and BH4 and GCH-1 concentration. OxLDL reduced NO production and BH4 and GCH-1 concentration but enhanced O generation and eNOS association with HSP90, and impaired endothelium-dependent vasodilation. D-4F inhibited the overall effects of oxLDL.

Conclusions: Hypercholesterolemia enhanced uncoupled eNOS activity by decreasing GCH-1 concentration, thereby reducing BH4 levels. D-4F reduced uncoupled eNOS activity by increasing BH4 levels through GCH-1 expression and decreasing eNOS phosphorylation and eNOS-HSP90 association. Our findings elucidate a novel mechanism by which hypercholesterolemia induces atherosclerosis and D-4F inhibits it, providing a potential therapeutic approach.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.019DOI Listing
July 2021

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-FeO Nanotherapy Drugs.

Materials (Basel) 2021 Apr 7;14(8). Epub 2021 Apr 7.

Department of Chemistry, National Sun Yat-sen University, 70 Lien-Hai Rd., Kaohsiung 80424, Taiwan.

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both FeO and doxorubicin (DOX) with agar as the drug carrier to obtain [email protected] The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, [email protected] reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.
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http://dx.doi.org/10.3390/ma14081824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067861PMC
April 2021

Simvastatin inhibits POVPC-mediated induction of endothelial-to-mesenchymal cell transition.

J Lipid Res 2021 Mar 10;62:100066. Epub 2021 Mar 10.

National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, People's Republic of China; NHC key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, People's Republic of China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, People's Republic of China; Division of Hypertension and Vascular Diseases, Department of Cardiology, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Endothelial-to-mesenchymal transition (EndMT), the process by which an endothelial cell (EC) undergoes a series of molecular events that result in a mesenchymal cell phenotype, plays an important role in atherosclerosis. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), derived from the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine, is a proinflammatory lipid found in atherosclerotic lesions. Whether POVPC promotes EndMT and how simvastatin influences POVPC-mediated EndMT remains unclear. Here, we treated human umbilical vein ECs with POVPC, simvastatin, or both, and determined their effect on EC viability, morphology, tube formation, proliferation, and generation of NO and superoxide anion (O). Expression of specific endothelial and mesenchymal markers was detected by immunofluorescence and immunoblotting. POVPC did not affect EC viability but altered cellular morphology from cobblestone-like ECs to a spindle-like mesenchymal cell morphology. POVPC increased O generation and expression of alpha-smooth muscle actin, vimentin, Snail-1, Twist-1, transforming growth factor-beta (TGF-β), TGF-β receptor II, p-Smad2/3, and Smad2/3. POVPC also decreased NO production and expression of CD31 and endothelial NO synthase. Simvastatin inhibited POVPC-mediated effects on cellular morphology, production of O and NO, and expression of specific endothelial and mesenchymal markers. These data demonstrate that POVPC induces EndMT by increasing oxidative stress, which stimulates TGF-β/Smad signaling, leading to Snail-1 and Twist-1 activation. Simvastatin inhibited POVPC-induced EndMT by decreasing oxidative stress, suppressing TGF-β/Smad signaling, and inactivating Snail-1 and Twist-1. Our findings reveal a novel mechanism of atherosclerosis that can be inhibited by simvastatin.
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http://dx.doi.org/10.1016/j.jlr.2021.100066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063863PMC
March 2021

Inpatient Virtual Vision Clinic Improves Access to Vision Rehabilitation Before and During the COVID-19 Pandemic.

Arch Rehabil Res Clin Transl 2021 Mar 19;3(1):100100. Epub 2020 Dec 19.

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

Objective: To describe and evaluate a secure video call system combined with a suite of iPad vision testing apps to improve access to vision rehabilitation assessment for inpatients.

Design: Retrospective.

Setting: Two acute care inpatient rehabilitation hospitals and 1 long-term acute care (LTAC) hospital.

Participants: Records of inpatients seen by the vision service.

Interventions: Records from a 1-year telemedicine pilot performed at acute rehabilitation (AR) hospital 1 and then expanded to AR hospital 2 and LTAC hospital during coronavirus disease 2019 (COVID-19) were reviewed. In the virtual visits, an occupational therapist measured the patients' vision with the iPad applications and forwarded results to the off-site Doctor of Optometry (OD) for review prior to a video visit. The OD provided diagnosis and education, press-on prism application supervision, strategies and modifications, and follow-up recommendations. Providers completed the telehealth usability questionnaire (10-point scale).

Main Outcome Measures: Vision examinations per month at AR hospital 1 before and with telemedicine.

Results: With telemedicine at AR hospital 1, mean visits per month significantly increased from 10.7±5 to 14.9±5 (=.002). Prism was trialed in 40% of cases of which 83% were successful, similar to previously reported in-person success rates. COVID-19 caused only a marginal decrease in visits per month (=.08) at AR1, whereas the site without an established program (AR hospital 2) had a 3-4 week gap in care while the program was initiated. Cases at the LTAC hospital tended to be more complex and difficult to manage virtually. The telehealth usability questionnaire median category scores were 7 for , 8 for , 6 for , and 9 for .

Conclusions: The virtual vision clinic process improved inpatient access to eye and visual neurorehabilitation assessment before and during the COVID-19 quarantine and was well accepted by providers and patients.
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http://dx.doi.org/10.1016/j.arrct.2020.100100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749728PMC
March 2021

Potential impact of COVID-19 pandemic on vaccination coverage in children: A case study of measles-containing vaccine administration in the United States (US).

Vaccine 2021 02 9;39(8):1201-1204. Epub 2020 Dec 9.

Merck & Co., Inc., Kenilworth, NJ, USA.

Background: The COVID-19 pandemic and stay-at-home orders have caused an unprecedented decrease in the administration of routinely recommended vaccines. However, the impact of this decrease on overall vaccination coverage in a specific birth cohort is not known.

Methods: We projected measles vaccination coverage for the cohort of children becoming one year old in 2020 in the United States, for different durations of stay-at-home orders, along with varying catch-up vaccination efforts.

Results: A 15% sustained catch-up rate outside stay-at-home orders (compared to what would be expected via natality information) may be necessary to achieve projected vaccination coverage similar to previous years. Permanent decreases in vaccine administration could lead to projected vaccination coverage levels below 80%.

Conclusion: Modeling measles vaccination coverage under a range of scenarios provides useful information about the potential magnitude and impact of under-immunization. Sustained catch-up efforts are needed to assure that measles vaccination coverage remains high.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723783PMC
February 2021

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients.

Redox Biol 2020 09 9;36:101642. Epub 2020 Jul 9.

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, PR China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, PR China. Electronic address:

Normal high-density lipoprotein (nHDL) in normal, healthy subjects is able to promote angiogenesis, but the mechanism remains incompletely understood. HDL from patients with coronary artery disease may undergo a variety of oxidative modifications, rendering it dysfunctional; whether the angiogenic effect is mitigated by such dysfunctional HDL (dHDL) is unknown. We hypothesized that dHDL compromises angiogenesis. The angiogenic effects of nHDL and dHDL were assessed using endothelial cell culture, endothelial sprouts from cardiac tissue from C57BL/6 mice, zebrafish model for vascular growth and a model of impaired vascular growth in hypercholesterolemic low-density lipoprotein receptor null(LDLr)mice. MiRNA microarray and proteomic analyses were used to determine the mechanisms. Lipid hydroperoxides were greater in dHDL than in nHDL. While nHDL stimulated angiogenesis, dHDL attenuated these responses. Protein and miRNA profiles in endothelial cells differed between nHDL and dHDL treatments. Moreover, nHDL suppressed miR-24-3p expression to increase vinculin expression resulting in nitric oxide (NO) production, whereas dHDL delivered miR-24-3p to inhibit vinculin expression leading to superoxide anion (O) generation via scavenger receptor class B type 1. Vinculin was required for endothelial nitric oxide synthase (eNOS) expression and activation and modulated the PI3K/AKT/eNOS and ERK1/2 signaling pathways to regulate nHDL- and VEGF-induced angiogenesis. Vinculin overexpression or miR-24-3p inhibition reversed dHDL-impaired angiogenesis. The expressions of vinculin and eNOS and angiogenesis were decreased, but the expression of miR-24-3p and lipid hydroperoxides in HDL were increased in the ischemic lower limbs of hypercholesterolemic LDLr mice. Overexpression of vinculin or miR-24-3p antagomir restored the impaired-angiogenesis in ischemic hypercholesterolemic LDLr mice. Collectively, nHDL stimulated vinculin and eNOS expression to increase NO production by suppressing miR-24-3p to induce angiogenesis, whereas dHDL inhibited vinculin and eNOS expression to enhance O generation by delivering miR-24-3p to impair angiogenesis, and that vinculin and miR-24-3p may be therapeutic targets for dHDL-impaired angiogenesis.
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http://dx.doi.org/10.1016/j.redox.2020.101642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364160PMC
September 2020

Novel Syntrophic Isovalerate-Degrading Bacteria and Their Energetic Cooperation with Methanogens in Methanogenic Chemostats.

Environ Sci Technol 2020 08 24;54(15):9618-9628. Epub 2020 Jul 24.

College of Architecture and Environment, Sichuan University, No. 24, South Section 1, First Ring Road, Chengdu, Sichuan 610065, China.

Isovalerate is an important intermediate in anaerobic degradation of proteins/amino acids. Little is known about how this compound is degraded due to challenges in cultivation and characterization of isovalerate-degrading bacteria, which are thought to symbiotically depend on methanogenic archaea. In this study, we successfully enriched novel syntrophic isovalerate degraders (uncultivated Clostridiales and Syntrophaceae members) through operation of mesophilic and thermophilic isovalerate-fed anaerobic reactors. Metagenomics- and metatranscriptomics-based metabolic reconstruction of novel putative syntrophic isovalerate metabolizers uncovered the catabolic pathway and byproducts (i.e., acetate, H, and formate) of isovalerate degradation, mechanisms for electron transduction from isovalerate degradation to H and formate generation (via electron transfer flavoprotein; ETF), and biosynthetic metabolism. The identified organisms tended to prefer formate-based interspecies electron transfer with methanogenic partners. The byproduct acetate was further converted to CH and CO by either (mesophilic) and (thermophilic), which employed different approaches for acetate degradation. This study presents insights into novel mesophilic and thermophilic isovalerate degraders and their interactions with methanogens.
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http://dx.doi.org/10.1021/acs.est.0c01840DOI Listing
August 2020

Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine.

Am J Physiol Endocrinol Metab 2020 07 9;319(1):E217-E231. Epub 2020 Jun 9.

Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

We previously demonstrated that circulating extracellular vesicles (EVs) from patients with valvular heart disease (VHD; vEVs) contain inflammatory components and inhibit endothelium-dependent vasodilation. Neutrophil chemotaxis plays a key role in renal dysfunction, and dexmedetomidine (DEX) can reduce renal dysfunction in cardiac surgery. However, the roles of vEVs in neutrophil chemotaxis and effects of DEX on vEVs are unknown. Here, we investigated the impact of vEVs on neutrophil chemotaxis in kidneys and the influence of DEX on vEVs. Circulating EVs were isolated from healthy subjects and patients with VHD. The effects of EVs on chemokine generation, forkhead box protein O3a (FOXO3a) pathway activation and neutrophil chemotaxis on cultured human umbilical vein endothelial cells (HUVECs) and kidneys in mice and the influence of DEX on EVs were detected. vEVs increased FOXO3a expression, decreased phosphorylation of Akt and FOXO3a, promoted FOXO3a nuclear translocation, and activated the FOXO3a signaling pathway in vitro. DEX pretreatment reduced vEV-induced CXCL4 and CCL5 expression and neutrophil chemotaxis in cultured HUVECs via the FOXO3a signaling pathway. vEVs were also found to suppress Akt phosphorylation and activate FOXO3a signaling to increase plasma levels of CXCL4 and CCL5 and neutrophil accumulation in kidney. The overall mechanism was inhibited in vivo with DEX pretreatment. Our data demonstrated that vEVs induced CXCL4-CCL5 to stimulate neutrophil infiltration in kidney, which can be inhibited by DEX via the FOXO3a signaling. Our findings reveal a unique mechanism involving vEVs in inducing neutrophils chemotaxis and may provide a novel basis for using DEX in reducing renal dysfunction in valvular heart surgery.
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http://dx.doi.org/10.1152/ajpendo.00062.2020DOI Listing
July 2020

Microparticles (Exosomes) and Atherosclerosis.

Curr Atheroscler Rep 2020 05 28;22(6):23. Epub 2020 May 28.

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China.

Purpose Of Review: This review summarizes the effects of microparticles and exosomes in the progression of atherosclerosis and the prospect for their diagnostic and therapeutic potentials.

Recent Findings: Microparticles and exosomes can induce endothelial dysfunction, vascular inflammation, coagulation, thrombosis, and calcification via their components of proteins and noncoding RNAs, which may promote the progression of atherosclerosis. The applications of microparticles and exosomes become the spotlight of clinical diagnosis and therapy. Microparticles and exosomes are members of extracellular vesicles, which are generated in various cell types by different mechanisms of cell membrane budding and multivesicular body secretion, respectively. They are important physiologic pathways of cell-to-cell communication in vivo and act as messengers accelerating or alleviating the process of atherosclerosis. Microparticles and exosomes may become diagnostic biomarkers and therapeutic approaches of atherosclerosis.
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http://dx.doi.org/10.1007/s11883-020-00841-zDOI Listing
May 2020

Acclimation Improves Methane Production from Molasses Wastewater with High Salinity in an Upflow Anaerobic Filter Reactor: Performance and Microbial Community Dynamics.

Appl Biochem Biotechnol 2020 May 4;191(1):397-411. Epub 2020 Feb 4.

College of Architecture and Environment, Sichuan University, Chengdu, 610065, China.

This study evaluated the performance of an upflow anaerobic filter (UAF) reactor in the thermophilic methane fermentation of hypersaline molasses wastewater. The high salinity (~ 45 mS/cm) of the undiluted wastewater completely inhibited the biogas production. An acclimation strategy involving gradient dilution of the molasses wastewater was implemented to gradually increase the salt stress. Consequently, the biogas production was recovered, inhibited only slightly by the high salinity of the undiluted wastewater. The reactor steadily achieved a high total organic carbon (TOC) loading rate of 5 g/L/day, with approximately 60% TOC removal efficiency. Acclimation to the gradually increased salt stress leads to a relative abundance of some halotolerant microbes, such as bacteria from Arcobacter, Tissierella, and Ruminococcaceae, which increased as their hydrolytic and acidogenic abilities adjusted to the incremental increase in salinity. Additionally, hydrogenotrophic methanogens, especially Methanoculleus, showed greater resistance to hypersalinity than aceticlastic methanogens. These results suggest that acclimation of the fermentation microbial community to hypersalinity is an effective strategy to improve methane production from hypersaline molasses wastewater in thermophilic UAF reactors.
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http://dx.doi.org/10.1007/s12010-020-03236-7DOI Listing
May 2020

Different Interspecies Electron Transfer Patterns during Mesophilic and Thermophilic Syntrophic Propionate Degradation in Chemostats.

Microb Ecol 2020 Jul 25;80(1):120-132. Epub 2020 Jan 25.

College of Architecture and Environment, Sichuan University, No. 24, South Section 1, First Ring Road, Chengdu, 610065, Sichuan, China.

Propionate is one of the major intermediates in anaerobic digestion of organic waste to CO and CH. In methanogenic environments, propionate is degraded through a mutualistic interaction between symbiotic propionate oxidizers and methanogens. Although temperature heavily influences the microbial ecology and performance of methanogenic processes, its effect on syntrophic interaction during propionate degradation remains poorly understood. In this study, metagenomics and metatranscriptomics were employed to compare mesophilic and thermophilic propionate degradation communities. Mesophilic propionate degradation involved multiple syntrophic organisms (Syntrophobacter, Smithella, and Syntrophomonas), pathways, interactions, and preference toward formate-based electron transfer to methanogenic partners (i.e., Methanoculleus). In thermophilic propionate degradation, one syntrophic organism predominated (Pelotomaculum), interspecies H transfer played a major role, and phylogenetically and metabolically diverse H-oxidizing methanogens were present (i.e., Methanoculleus, Methanothermobacter, and Methanomassiliicoccus). This study showed that microbial interactions, metabolic pathways, and niche diversity are distinct between mesophilic and thermophilic microbial communities responsible for syntrophic propionate degradation.
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http://dx.doi.org/10.1007/s00248-020-01485-xDOI Listing
July 2020

Response of Isovalerate-Degrading Methanogenic Microbial Community to Inhibitors.

Appl Biochem Biotechnol 2020 Jul 17;191(3):1010-1026. Epub 2020 Jan 17.

College of Architecture and Environment, Sichuan University, No. 24, South Section 1, First Ring Road, Chengdu, 610065, Sichuan, China.

Isovalerate is one of the key intermediates during anaerobic digestion treating protein-containing waste/wastewater. Investigating the effect of different kinds of inhibitors on isovalerate-degrading microbial community is necessary to develop measures for improving the effectiveness of the treatment plants. In the present study, dynamic changes in the isovalerate-degrading microbial community in presence of inhibitors (ammonium, sulfide, mixed ammonium and sulfide, and chlortetracycline (CTC)) were investigated using high-throughput sequencing of 16S rRNA gene. Our observations showed that the isovalerate-degrading microbial community responded differently to different inhibitors and that the isovalerate degradation and gas production were strongly repressed by each inhibitor. We found that sulfide inhibited both isovalerate oxidation followed by methanogenesis, while ammonium, mixed ammonium and sulfide, and CTC mainly inhibited isovalerate oxidation. Genera classified into Proteobacteria and Chloroflexi were less sensitive to inhibitors. The two dominant genera, which are potential syntrophic isovalerate oxidizers, exhibited different responses to inhibitors that the unclassified_Peptococcaceae_3 was more sensitive to inhibitors than the unclassified_Syntrophaceae. Upon comparison to acetoclastic methanogen Methanosaeta, hydrogenotrophic methanogens Methanoculleus and Methanobacterium were less sensitive to inhibitors.
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http://dx.doi.org/10.1007/s12010-020-03234-9DOI Listing
July 2020

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines.

Neurosci Bull 2020 May 11;36(5):530-544. Epub 2019 Dec 11.

State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.
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http://dx.doi.org/10.1007/s12264-019-00451-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186293PMC
May 2020

A novel 40kDa N-terminal truncated carboxypeptidase E splice variant: cloning, cDNA sequence analysis and role in regulation of metastatic genes in human cancers.

Genes Cancer 2019 ;10(5-6):160-170

Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Carboxypeptidase E (CPE), a prohormone processing enzyme, is a 476- amino acid protein with a signal peptide in its N-terminus and is expressed in the nervous and the endocrine systems. Recent evidence indicate CPE plays various non-enzymatic roles in the endocrine and nervous systems and in various cancers. Besides wild type (WT) CPE, a 40-kDa CPE protein that localizes in the nucleus and cytoplasm has been described in embryonic mouse brain. In this study we have cloned this CPE variant encoding the 40kDa CPE-ΔN protein from human cancer cells. RACE assay and sequence analysis confirmed existence of this CPE variant mRNA, which has 198 nucleotides removed within the first exon and 589 nucleotides from the 3'-UTR, respectively, compared to WT-CPE mRNA. Bioinformatic analysis revealed that this CPE variant mRNA has a shortened open reading frame, which starts coding from the 3rd ATG relative to WT-CPE mRNA and encodes a 40kDa N-terminus truncated CPE protein. RT-PCR and Western blot analysis showed that 40kDa CPE-ΔN is expressed in multiple cancer cell lines and tumor tissues. Overexpression of this 40kDa CPE-ΔN variant up-regulated expression of multiple metastatic genes encompassing different signaling pathways, suggesting potentially an important role of CPE-ΔN in tumor metastasis.
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http://dx.doi.org/10.18632/genesandcancer.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872665PMC
January 2019

Insights into the ecological roles and evolution of methyl-coenzyme M reductase-containing hot spring Archaea.

Nat Commun 2019 10 8;10(1):4574. Epub 2019 Oct 8.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, 510275, Guangzhou, PR China.

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.
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http://dx.doi.org/10.1038/s41467-019-12574-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783470PMC
October 2019

A nonsense mutant of the hepatitis B virus large S protein antagonizes multiple tumor suppressor pathways through c-Jun activation domain-binding protein1.

PLoS One 2019 14;14(3):e0208665. Epub 2019 Mar 14.

Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.

Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Previous studies have identified recurrent nonsense mutations in the HBV large S (LHBs) gene from the liver from HBV core antigen-positive HCC patients. These nonsense mutants have been shown to be oncogenic in mouse xenograft models using a mouse embryonic fibroblast cell line. Here, we expressed in a liver cell line Huh-7 a carboxy terminally truncated protein from a nonsense mutant of the LHBs gene, sW182* (stop codon at tryptophane-182). Although the sW182* protein appeared not to be very stable in the cultured liver cells, we confirmed that the protein can be highly expressed and retained for a prolonged period of time in the hepatocytes in the mouse liver, indicating its stable nature in the physiological condition. In the Huh-7 cells, the sW182* mutant downregulated tumor suppressors p53 and Smad4. This downregulation was reversed by a proteasome inhibitor MG132, implying the involvement of proteasome-based protein degradation in the observed regulation of the tumor suppressors. On the other hand, we found that c-Jun activation domain-binding protein 1 (Jab1) physically interacts with the sW182*, but not wild-type LHBs. RNA interference (RNAi) of Jab1 restored the levels of the downregulated p53 and Smad4. The sW182* mutant inhibited the promoter activity of downstream target genes of the tumor suppressors. Consistently, Jab1 RNAi reversed the inhibition. These results suggest that the LHBs nonsense mutant antagonizes the tumor suppressor pathways through Jab1 in the liver contributing to HCC development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208665PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417713PMC
November 2019

An Ultrasensitive Colorimetric Strategy for Detection of Cadmium Based on the Peroxidase-like Activity of G-Quadruplex-Cd(II) Specific Aptamer.

Anal Sci 2019 Mar 2;35(3):277-282. Epub 2018 Nov 2.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology.

We rationally designed an ultrasensitive and label-free sensing platform for determination of cadmium (Cd). The sensing platform contains G-quadruplex-Cd(II) specific aptamer (GCDSA) constructed by incorporating G-rich sequence at the end of 5' and the critical domain of the Cd-4 aptamer. GCDSA designed act as both a special recognition sequence for Cd and a signal DNAzyme. In absence of Cd, GCDSA may mainly exist in a random coil sequence. Upon addition of Cd, GCDSA could probably be induced to fold into a G-quadruplex structure. The generation of plentiful active G-quadruplex interacts with hemin to form a peroxidase-like DNAzyme, leading to increased absorbance signal of the sensing system. ΔA was directly proportional to the two segments of concentrations for Cd, with the detection of limit of 0.15 nM. The proposed method avoids the labeled oligonucleotides and allows directly quantitative analysis of the samples by cheap instruments, with an excellent dynamic range.
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http://dx.doi.org/10.2116/analsci.18P248DOI Listing
March 2019

as a Potential Metastasis Suppressor Gene in Human Colorectal Cancer.

Int J Mol Sci 2018 May 3;19(5). Epub 2018 May 3.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Monocyte chemotactic protein induced protein 3 (MCPIP3) belongs to the Cys⁻Cys⁻Cys⁻His (CCCH)-zinc finger protein family and contains a highly conserved CCCH-zinc finger domain and a Nedd4-BP1 YacP nuclease (NYN) domain. Previous studies showed that MCPIP3 inhibits the expression of proinflammatory genes, such as vascular cell adhesion molecule ()-1, in human endothelial cells, but the roles and functions of MCPIP3 in cancer cells are still unknown. In human colorectal cancer specimens, we found that the messenger RNA expression of was significantly downregulated in cancer tissues compared to adjacent normal tissues (18/25; average fold change of 8.18). Two cell models were used to demonstrate the anti-migration activity of MCPIP3. First, Tet-on T-REx-293/HA-MCPIP3 cells were used to examine whether MCPIP3 can change epithelial⁻mesenchymal transition (EMT)-related gene expressions. Second, we used two human colorectal cancer cell lines, SW620 and HCT116, to prove the role of MCPIP3 in regulating EMT-related gene expressions. We found that overexpression of MCPIP3 inhibited cell migration according to a wound-healing assay and Transwell invasion assay and vimentin expression, and increased -cadherin expression in these two cell lines. These results suggest that MCPIP3 might play a negative role in cell migration of human colorectal cancer cells.
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http://dx.doi.org/10.3390/ijms19051350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983627PMC
May 2018

High intensity lifestyle intervention and long-term impact on weight and clinical outcomes.

PLoS One 2018 18;13(4):e0195794. Epub 2018 Apr 18.

HMR Weight Management Services Corp., Boston, Massachusetts, United States of America.

Background: Obesity increases the risk for diabetes and cardiovascular events, with a corresponding growth in medical costs. High intensity lifestyle intervention (HILI) is the cornerstone for weight management. We assessed the effectiveness of clinic-based HILI on weight loss and associated clinical outcomes by duration of program participation and comorbid conditions.

Methods: This was a retrospective cohort study of patients who enrolled in HILI weight management programs at Health Management Resources (HMR) clinics located across the U.S. Patients completed health risk assessments (HRA) and were enrolled for up to 24 months at the time of follow-up HRA. HMR programs provide weekly group coaching to achieve reduced calorie intake, increased fruit/vegetable intake, and physical activity ≥2,000 kcal/wk. A Markov model predicted avoidance of diabetes and cardiovascular events and projected cost savings due to weight loss.

Results: Of the 500 patients included in the analysis, 67% were female and mean age was 54.1 years (s.d. 11.6). The baseline weight and BMI were 243.5 lbs (range 144.0-545.0) and 38.8 kg/m2 (range 25.4-85.0), respectively. Overall, patients lost an average of 47.4 lbs (18.9% of initial body weight [IBW]); the amount of weight loss was consistent among those with diabetes/pre-diabetes (50%), high/moderate risk for dyslipidemia (60%), hypertension/pre-hypertension (86%), and severe obesity (37%). The mean IBW lost was 16.4%, 19.3%, 20.7% for ≤6 months (n = 165), 7-12 months (n = 140), 13-24 months (n = 195) of program participation, respectively. The simulation model estimated 22 diabetes and 30 cardiovascular events and $1,992,370 medical costs avoided over 5 years in the 500 patients evaluated.

Conclusion: Patients in the HMR clinic-based HILI program achieved substantial weight loss regardless of duration of program participation, risk profile and comorbid status. The HMR program could be an effective strategy to prevent costly diabetes and cardiovascular events, particularly in high risk patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195794PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905976PMC
July 2018

Functional but Inefficient Kinesthetic Motor Imagery in Adolescents with Autism Spectrum Disorder.

J Autism Dev Disord 2018 03;48(3):784-795

School of Occupational Therapy, College of Medicine, National Taiwan University, F4, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 100, Taiwan.

Whether action representation in individuals with autism spectrum disorder (ASD) is deficient remains controversial, as previous studies of action observation or imitation report conflicting results. Here we investigated the characteristics of action representation in adolescents with ASD through motor imagery (MI) using a hand rotation and an object rotation task. Comparable with the typically-developing group, the individuals with ASD were able to spontaneously use kinesthetic MI to perform the hand rotation task, as manifested by the significant biomechanical effects. However, the ASD group performed significantly slower only in the hand rotation task, but not in the object rotation task. The findings suggest that the adolescents with ASD showed inefficient but functional kinesthetic MI, implicating that their action representation might be preserved.
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http://dx.doi.org/10.1007/s10803-017-3367-yDOI Listing
March 2018
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