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arXiv 2022年

作者： Ali Heydari, A. Davalos, Oscar A. Hoyer, Katrina K. Sindi, Suzanne S. Department of Applied Mathematics University of California United States Health Sciences Research Institute Quantitative and Systems Biology Graduate Program Department of Molecular and Cell Biology University of California Merced United States

Single-cell RNA sequencing (scRNAseq) is rapidly advancing our understanding of cellular composition within complex tissues and organisms. A major limitation in most scRNAseq analysis pipelines is the reliance on manual annotations to determine cell identities, which are time consuming, subjective, and require expertise. Given the surge in cell sequencing, supervised methods–especially deep learning models–have been developed for automatic cell type identification (ACTI), which achieve high accuracy and scalability. However, all existing deep learning frameworks for ACTI lack interpretability and are used as "black-box" models. We present N-ACT (Neural-Attention for Cell Type identification): the first-of-its-kind interpretable deep neural network for ACTI utilizing neural attention to detect salient genes for use in cell-types identification. We compare N-ACT to conventional annotation methods on two previously manually annotated data sets, demonstrating that N-ACT accurately identifies marker genes and cell types in an unsupervised manner, while performing comparably on multiple data sets to current state-of-the-art model in traditional supervised ACTI. © 2022, CC BY.

关键词： Genes

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Baccharis trimera aqueous extract modulates inflammation and nociception in mice

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Clinical Phytoscience 2021年第1期7卷 1-10页

作者： de Almeida, Natiely Silveira Ferraz, Alexandre de Barros Falcão Pedron, Claudia Correa, Dione Silva Vieira, Luciene Bruno Antunes, Flavia Tasmim Techera de Souza, Alessandra Hubner Graduate Program in Genetics and Toxicology (PPGGTA) Lutheran University of Brazil Canoas Brazil Graduate Program in Cellular and Molecular Biology Applied to Health Lutheran University of Brazil Canoas Brazil Departamento de Farmacologia ICB Universidade Federal de Minas Gerais Belo Horizonte Brazil

The aerial parts of Baccharis trimera (Less.) are frequently used as a tea to treat several diseases. Therefore, the aim of this study was to identify the constituents of an aqueous extract of B. trimera, focusing on their antioxidant, anti-inflammation, and antinociception activities and properties. For that, the researchers performed in vivo assays using the formalin test and Freund’s Complete Adjuvant (FCA) to measure the acute and chronic inflammatory pain in mice. Moreover, the myeloperoxidase enzyme (MPO) was analyzed in the subcutaneous tissue after the FCA injection, together with the counting of lymphocytes in the peripheral blood of the mice. The qualitative phytochemical analysis indicated the presence of flavonoids and saponins in the B. trimera aqueous extract. The high-performance liquid chromatography (HPLC) analyses showed the presence of phenolic compounds, such as chlorogenic acid, ellagic acid, rosmarinic acid, as well as flavonoids, such as rutin, quercetin, and luteolin. The DPPH assay was used in order to measure the antioxidant activity of the aqueous extract of B. trimera and this showed an IC50 of 118.18 ± 1.02 μg/mg. The data from the formalin test demonstrated that a single dose of the aqueous extract of B. trimera was not able to decrease the nociceptive behavior during the neurogenic phase, at any of the tested doses (20, 40, or 80 mg/kg p.o.). However, during the inflammatory phase of this test, the aqueous extract of B. trimera at 80 mg/kg (p.o.) significantly decreased the nociceptive behavior, showing more effectiveness when compared to the other tested doses (p < 0.05). Importantly, in the chronic inflammatory model on the 5th day of treatment, the aqueous extract of B. trimera (80 mg/kg p.o.) significantly reduced mechanical allodynia (p < 0.01), heat thermal hyperalgesia (p < 0.001), and paw edema (p < 0.05). There were no changes in the MPO activity, but the data exhibited an equivalent decrease in the number of lymph

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New candidate genes potentially involved in Zika virus teratogenesis

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Computers in Biology and Medicine 2024年 173卷 108259-108259页

作者： Ferrão Maciel-Fiuza, Miriãn Rengel, Bruna Duarte Wachholz, Gabriela Elis do Amaral Gomes, Julia de Oliveira, Maikel Rosa Kowalski, Thayne Woycinck Roehe, Paulo Michel Luiz Vianna, Fernanda Sales Schüler-Faccini, Lavínia Mayer, Fabiana Quoos Varela, Ana Paula Muterle Fraga, Lucas Rosa Graduate Program in Genetics and Molecular Biology Universidade Federal do Rio Grande do Sul Porto Alegre Brazil Instituto Nacional de Genética Médica Populacional Porto Alegre Brazil Genomics Medicine Laboratory Center of Experimental Research Hospital de Clínicas de Porto Alegre Porto Alegre Brazil Department of Morphological Sciences Institute of Health Sciences Universidade Federal do Rio Grande do Sul Porto Alegre Brazil Graduate Program in Medicine: Medical Sciences Universidade Federal do Rio Grande do Sul Porto Alegre Brazil Teratogen Information System Medical Genetics Service Hospital de Clínicas de Porto Alegre Porto Alegre Brazil Bioinformatics Core Hospital de Clínicas de Porto Alegre Porto Alegre Brazil Centro Universitário CESUCA Cachoeirinha Brazil Department of Microbiology Immunology and Parasitology Institute of Health Sciences Universidade Federal do Rio Grande do Sul Porto Alegre Brazil Graduate Program in Molecular and Cellular Biology Biotechnology Center Universidade Federal do Rio Grande do Sul Porto Alegre Brazil Graduate Program in Biosciences Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre Brazil

Despite efforts to elucidate Zika virus (ZIKV) teratogenesis, still several issues remain unresolved, particularly on the molecular mechanisms behind the pathogenesis of Congenital Zika Syndrome (CZS). To answer this question, we used bioinformatics tools, animal experiments and human gene expression analysis to investigate genes related to brain development potentially involved in CZS. Searches in databases for genes related to brain development and CZS were performed, and a protein interaction network was created. The expression of these genes was analyzed in a CZS animal model and secondary gene expression analysis (DGE) was performed in human cells exposed to ZIKV. A total of 2610 genes were identified in the databases, of which 1013 were connected. By applying centrality statistics of the global network, 36 candidate genes were identified, which, after selection resulted in nine genes. Gene expression analysis revealed distinctive expression patterns for PRKDC, PCNA, ATM, SMC3 as well as for FGF8 and SHH in the CZS model. Furthermore, DGE analysis altered expression of ATM, PRKDC, PCNA. In conclusion, systems biology are helpful tools to identify candidate genes to be validated in vitro and in vivo. PRKDC, PCNA, ATM, SMC3, FGF8 and SHH have altered expression in ZIKV-induced brain malformations. © Elsevier Ltd

关键词： Viruses

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A cytological analysis of the oral mucosa adjacent to orthodontic devices

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European Journal of General Dentistry 2021年第2期2卷 119-123页

作者： Raul Magnoler Sampaio Mei Antônio Adilson Soares de Lima Jorge César Borges Leão Filho Orlando Motohiro Tanaka Odilon Guariza Filho Elisa Souza Camargo Graduate Dentistry Program Orthodontics Centro Universitário da Grande Dourados Dourados Brazil Depatment for Stomatology Universidade Federal do Paraná Curitiba Brazil Pontifícia Universidade Católica do Paraná Curitiba School of Health and Biosciences Dentistry Graduate Program - Orthodontics Brazil

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BRD4uclear PD-L1/RelB circuit is involved in the stemness of breast cancer cells

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Cell Communication and Signaling 2023年第1期21卷 1-21页

作者： Kim, Su-Lim Choi, Hack Sun Lee, Dong-Sun Bio-Health Materials Core-Facility Center Jeju National University Jeju Republic of Korea Graduate Program for Bio-health/Innovative Drug Development using Subtropical Bio-Resources Jeju National University Jeju Republic of Korea Subtropical/Tropical Organism Gene Bank Jeju National University Jeju Republic of Korea Faculty of Biotechnology College of Applied Life Sciences Jeju National University SARI Jeju Republic of Korea

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. BC stem cells (BCSCs) have been known to be involved in the carcinogenesis of the breast and contribute to therapeutic resistance. The programmed death-ligand 1 (PD-L1) expression of BC correlated with a poor prognosis. Immunotherapies that target PD-L1 have great potential and have been successful when applied to cancer treatment. However, whether PD-L1 regulates BCSC formation is unknown. BCSCs were enriched by serum-free suspension culture. The properties of BCSCs were examined by mammosphere formation assay, CD44+/Cd24−, aldehyde dehydrogenase (ALDH) assay, CSC marker analysis, and mammosphere growth assay. To elucidate the functions of bromodomain-containing protein 4 (BRD4), nuclear PD-L1, and RelB proteins in the stemness of BCSCs, mammosphere formation was examined using BRD4 inhibitor and degrader, PD-L1 degrader, and RelB inhibitor. The antitumor function of 3',4',7,8-tetrahydroxyflavone (THF), a specific BRD4 inhibitor, was studied through in vivo tumor model and mouse studies, and the protein levels of c-Myc, PD-L1, and RelB were examined in tumor model under THF treatment. BRD4 was upregulated in breast CSCs and regulates the stemness of BCs. The downregulation of BRD4 using BRD4 PROTAC, ARV-825, and BRD4 inhibitor, (+)-JQ1, inhibits mammosphere formation and reduces the levels of breast CSC markers (CD44+/CD24− and ALDH1), stem cell marker genes, and mammosphere growth. BRD4 inhibitor (JQ1) and degrader (ARV825) downregulate membrane and nuclear fractions of PD-L1 through the inhibition of PD-L1 transcript levels. The knockdown of PD-L1 inhibits mammosphere formation. Verteporfin, a PD-L1 degrader, inhibits the transcripts and protein levels of PD-L1 and downregulates the transcript and protein levels of RelB. Calcitriol, a RelB inhibitor, and the knockdown of RelB using si-RelB regulate mammosphere formation through interleukin-6 (IL-6) expression. THF is a natural product and

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5-ALA mediated photodynamic therapy increases natural killer cytotoxicity against oral squamous cell carcinoma cell lines

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Journal of Biophotonics 2024年第9期17卷

作者： Molon, Angela Cristina Heguedusch, Daniele Nunes, Fabio Daumas Cecatto, Rebeca Boltes dos Santos Franco, Adriana Lino de Oliveira Rodini Pegoraro, Camila Rodrigues, Maria Fernanda Setúbal Destro Post Graduate Program in Biophotonics Applied to Health Sciences Nove de Julho University São Paulo Brazil Department of Stomatology Discipline of Oral and Maxillofacial Pathology School of Dentistry University of São Paulo São Paulo Brazil Department of Biological Sciences University of São Paulo Bauru School of Dentistry SP Bauru Brazil

Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies. © 2024 Wiley-VCH GmbH.

关键词： Photodynamic therapy

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An Lc-Ms Based Metabolomic Approach Coupled with Bioassay-Guided Fractionation to Identifying Bioactive Biflavonoids from Selaginella Willdenowii

SSRN

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SSRN 2025年

作者： Thasana, Nopporn Wongsuwan, Sutthida Jumpathong, Watthanachai Chatwichien, Jaruwan Thamnarak, Wanlaya Ngiwsara, Lukana Lirdprapamongkol, Kriengsak Svasti, Jisnuson Ruchirawat, Somsak Program in Chemical Sciences Chulabhorn Graduate Institute 54 Kamphaeng Phet 6 Road Laksi Bangkok10210 Thailand Chulabhorn Royal Academy 906 Kamphaeng Phet 6 Road Laksi Bangkok10210 Thailand OPS Ministry of Higher Education Science Research and Innovation Bangkok10400 Thailand Laboratory of Medicinal Chemistry Chulabhorn Research Institute 54 Kamphaeng Phet 6 Road Laksi Bangkok10210 Thailand Laboratory of Biochemistry Chulabhorn Research Institute Bangkok10210 Thailand Program in Applied Biological Sciences: Environmental Health Chulabhorn Graduate Institute 54 Kamphaeng Phet 6 Road Laksi Bangkok10210 Thailand

The wide-ranging applications of biflavonoids enriched in Selaginella plants, particularly in cuisines and medicines, have attracted interest in the isolation of bioactive biflavonoids. However, identification of bioactive compounds in a complex mixture is a crucial challenge in medicinal plant research. The data set of Selaginella willdenowii fractions having anti-inflammatory activity combined with their LC-MS-based metabolomic profiles was analyzed by the multivariate analysis. The findings suggested that tetrahydrobilobetin and 2′′,3′′-dihydrobilobetin were the potential anti-inflammatory agents. Furthermore, robustaflavone-7′′-methyl ether (9c) demonstrated the strongest cytotoxicity against three cancer cell lines (A549, HepG2, and T47D) with high selectivity for A549 cells. Further mechanistic investigation indicated that 9c induced apoptotic cell death through elevation of ROS level in A549 cells. Notably, this work highlights the potential of applying a metabolomic strategy coupled with bioassay-guided isolation, thereby accelerating research in drug discovery and providing a valuable source of ingredients for the development of value-added food products. © 2025, The Authors. All rights reserved.

关键词： Bioassay

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Trapped-Ion Quantum Simulation of Electron Transfer Models with Tunable Dissipation

arXiv

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arXiv 2024年

作者： So, Visal Suganthi, Midhuna Duraisamy Menon, Abhishek Zhu, Mingjian Zhuravel, Roman Pu, Han Wolynes, Peter G. Onuchic, José N. Pagano, Guido Department of Physics and Astronomy Rice University HoustonTX77005 United States Applied Physics Graduate Program Smalley-Curl Institute Rice University HoustonTX77005 United States Department of Chemistry Rice University HoustonTX77005 United States Center for Theoretical Biological Physics Rice University HoustonTX77005 United States Department of Biosciences Rice University HoustonTX77005 United States

Electron transfer is at the heart of many fundamental physical, chemical, and biochemical processes essential for life. The exact simulation of these reactions is often hindered by the large number of degrees of freedom and by the essential role of quantum effects. Here, we experimentally simulate a paradigmatic model of molecular electron transfer using a multispecies trapped-ion crystal, where the donor-acceptor gap, the electronic and vibronic couplings, and the bath relaxation dynamics can all be controlled independently. By manipulating both the ground-state and optical qubits, we observe the real-time dynamics of the spin excitation, measuring the transfer rate in several regimes of adiabaticity and relaxation dynamics. Our results provide a testing ground for increasingly rich models of molecular excitation transfer processes that are relevant for molecular electronics and light-harvesting systems. © 2024, CC BY-NC-ND.

关键词： Trapped ions

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Ancylostoma ceylanicum and other zoonotic canine hookworms:neglected public and animal health risks in the Asia-Pacific region

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Animal Diseases 2024年第1期4卷 59-74页

作者： Jan Clyden B.Tenorio lan Kim B.Tabios Tawin Inpankaew Adrian P.Ybanez Saruda Tiwananthagorn Sirikachorn Tangkawattana Sutas Suttiprapa Tropical Medicine Graduate Program Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Tropical Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand WHO Collaborating Center for Research and Control of Opisthorchiasis(Southeast Asian Liver Fluke Disease) Tropical Disease Research CenterKhon Kaen UniversityKhon Kaen 40002Thailand Department of Veterinary Paraclinical Sciences College of Veterinary MedicineUniversity of Southern MindanaoKabacan9407 CotabatoPhilippines Institute of Biology College of ScienceUniversity of the Philippines DilimanManila 1101Philippines Department of Parasitology Faculty of Veterinary MedicineKasetsart UniversityBangkok 10900Thailand College of Veterinary Medicine at Barili Campus and Center for Vector-Borne and Protozoan Diseases at Main Campus Cebu Technological UniversityCebu City 6000Philippines Department of Veterinary Biosciences and Public Health Faculty of Veterinary MedicineChiang Mai UniversityChiang Mai 50100Thailand Research Center for Veterinary Biosciences and Veterinary Public Health Chiang Mai UniversityChiang Mai 50100Thailand Faculty of Veterinary Medicine Khon Kaen University.Khon Kaen 40002Thailand

Zoonotic hookworm infections remain a significant public health problem,causing nearly 500 milion cases globally and approximately four million disability-adjusted life years lost *** than one-fth of these cases are attrib-uted to Ancylostoma ceylanicum,an emerging zoonotic health issue in the Asia-Pacific *** review presents key research gaps regarding the epidemiology,diagnosis,control,prevention and elimination of *** and other canine zoonotic hookworms as neglected health *** is the second most prevalent human hook-worm in the region;it is the most common hookworm among dogs and cats-reservoirs of zoonotic *** population genetic and phylogenetic analyses revealed that *** has three possible transmis-sion dynamics:zoonotic,animal-only,and human-only *** actual burden of zoonotic ancylostomiasis in most endemic countries remains unknown due to the use of parasitological techniques(e.g.,Kato-Katz thick smear and floatation techniques)that have reduced diagnostic performance and do not allow accurate species identifica-tion in helminth *** emergence of benzimidazole resistance in soil-transmitted helminths(STHs),includ-ing hookworms,is a concern due to the protracted implementation of mass drug administration(MDA).Resistance is conferred by single nucleotide polymorphisms(SNPs)that occur in theβ-tubulin isotype 1 *** mutations have been reported in drug-resistant *** but have not been found in *** in the *** remains understudied in the Asia-Pacific *** zoonotic nature of the parasite warrants investigation of its occur-rence in human and animal reservoir hosts to understand the dynamics of zoonotic transmission in different endemic *** detection of benzimidazole resistance-associated SNPs in zoonotic hookworms from Asia-Pacific countries has yet to be thoroughly *** the high level of hookworm endemicity in the region

关键词： Soil-transmitted helminths Neglected tropical diseases Mass drug administration Deworming Veterinary public health

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Neglecting Animal Sporotrichosis Notification in Brazil: A Challenge for One health Surveillance

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Acta tropica 2025年 267卷 107665页

作者： Paulo Ricardo Martins-Filho Silvia Maria da Silva Sant'Ana Rodrigues Thialla Andrade Carvalho Francy Waltilia Cruz Araújo André Luiz de Jesus Morais Ana Fátima Souza Melo de Andrade Danilo Santos de Sousa Martha Débora Lira Tenório Janiele de Sá Ferreira Roseane Nunes de Santana Campos Investigative Pathology Laboratory Federal University of Sergipe Lagarto SE 49400-000 Brazil Health Sciences Graduate Program Federal University of Sergipe Aracaju SE 49060-100 Brazil. Electronic address: prmartinsfh@***. Health Sciences Graduate Program Federal University of Sergipe Aracaju SE 49060-100 Brazil. Graduate Program in Applied Health Sciences Federal University of Sergipe Lagarto SE 49400-000 Brazil.

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