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BISCUIT: an efficient, standards-compliant tool suite for simultaneous genetic and epigenetic inference in bulk and single-cell studies.
Zhou, W, Johnson, BK, Morrison, J, Beddows, I, Eapen, J, Katsman, E, Semwal, A, Habib, WA, Heo, L, Laird, PW, et al
Nucleic acids research. 2024;(6):e32
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Abstract
Data from both bulk and single-cell whole-genome DNA methylation experiments are under-utilized in many ways. This is attributable to inefficient mapping of methylation sequencing reads, routinely discarded genetic information, and neglected read-level epigenetic and genetic linkage information. We introduce the BISulfite-seq Command line User Interface Toolkit (BISCUIT) and its companion R/Bioconductor package, biscuiteer, for simultaneous extraction of genetic and epigenetic information from bulk and single-cell DNA methylation sequencing. BISCUIT's performance, flexibility and standards-compliant output allow large, complex experimental designs to be characterized on clinical timescales. BISCUIT is particularly suited for processing data from single-cell DNA methylation assays, with its excellent scalability, efficiency, and ability to greatly enhance mappability, a key challenge for single-cell studies. We also introduce the epiBED format for single-molecule analysis of coupled epigenetic and genetic information, facilitating the study of cellular and tissue heterogeneity from DNA methylation sequencing.
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Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.
Shen, H, Zhu, R, Liu, Y, Hong, Y, Ge, J, Xuan, J, Niu, W, Yu, X, Qin, JJ, Li, Q
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2024;:101013
Abstract
Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.
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Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review.
Yan, X, Kong, J, Wang, J, Wang, C, Shen, H
BMC pulmonary medicine. 2024;(1):121
Abstract
BACKGROUND Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. CASE DESCRIPTION Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. CONCLUSIONS This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.
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Viral lysing can alleviate microbial nutrient limitations and accumulate recalcitrant dissolved organic matter components in soil.
Tong, D, Wang, Y, Yu, H, Shen, H, Dahlgren, RA, Xu, J
The ISME journal. 2023;(8):1247-1256
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Abstract
Viruses are critical for regulating microbial communities and biogeochemical processes affecting carbon/nutrient cycling. However, the role of soil phages in controlling microbial physiological traits and intrinsic dissolved organic matter (DOM) properties remains largely unknown. Herein, microcosm experiments with different soil phage concentrates (including no-added phages, inactive phages, and three dilutions of active phages) at two temperatures (15 °C and 25 °C) were conducted to disclose the nutrient and DOM dynamics associated with viral lysing. Results demonstrated three different phases of viral impacts on CO2 emission at both temperatures, and phages played a role in maintaining Q10 within bounds. At both temperatures, microbial nutrient limitations (especially P limitation) were alleviated by viral lysing as determined by extracellular enzyme activity (decreased Vangle with active phages). Additionally, the re-utilization of lysate-derived DOM by surviving microbes stimulated an increase of microbial metabolic efficiency and recalcitrant DOM components (e.g., SUV254, SUV260 and HIX). This research provides direct experimental evidence that the "viral shuttle" exists in soils, whereby soil phages increase recalcitrant DOM components. Our findings advance the understanding of viral controls on soil biogeochemical processes, and provide a new perspective for assessing whether soil phages provide a net "carbon sink" vs. "carbon source" in soils.
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Nutritional interventions in adult fibrostenotic Crohn's disease: A systematic review.
Cooper, JL, Rosentreter, RE, Filyk, A, Premji, ZA, Shen, H, Ingram, R, Kaplan, GG, Ma, C, Novak, K, Panaccione, R, et al
Frontiers in nutrition. 2023;:1017382
Abstract
BACKGROUND Management of Crohn's disease (CD) using dietary interventions has become an area of increased research interest. There is a lack of specific research exploring if diet and nutrition interventions are beneficial in patients with strictures, as current dietary recommendations in fibrostenotic CD are often based on clinical judgment. The aim of this systematic review was to assess the impact of dietary interventions in fibrostenotic CD on medical and surgical outcomes. METHODS A systematic search of MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (Ovid) was conducted. Studies reporting dietary interventions or nutritional factors in fibrostenotic CD were included. Outcomes for studies assessing dietary interventions such as enteral nutrition were evaluated as changes in (1) CD symptoms (CD Activity Index), (2) stricture parameters on diagnostic imaging, and (3) rates of surgical or medical intervention following dietary interventions. RESULTS Five studies were included in this review. Three studies assessed exclusive enteral nutrition (EEN), one evaluated total parenteral nutrition (TPN), and one studied a liquid diet. All included studies evaluated symptoms as an outcome, while diagnostic imaging parameters and surgical outcomes in the studies were either absent or too heterogeneous to appraise improvement post dietary intervention. Included EEN studies displayed similar efficacy, with approximately 60% of patients having symptom improvement. The included TPN study also reported 75% of patients with symptom improvement, while the liquid diet did not. CONCLUSION Exclusive enteral nutrition and total parental nutrition may provide benefit for use as a dietary intervention for fibrostenotic CD. There remains a need for high-quality controlled trials which utilize standardized definitions of strictures.
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Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.
Byrne, KL, Szeligowski, RV, Shen, H
Biomolecules. 2023;(9)
Abstract
Homology search and phylogenetic analysis have commonly been used to annotate gene function, although they are prone to error. We hypothesize that the power of homology search in functional annotation depends on the coupling of sequence variation to functional diversification, and we herein focus on the SoLute Carrier (SLC25) family of mitochondrial metabolite transporters to survey this coupling in a family-wide manner. The SLC25 family is the largest family of mitochondrial metabolite transporters in eukaryotes that translocate ligands of different chemical properties, ranging from nucleotides, amino acids, carboxylic acids and cofactors, presenting adequate experimentally validated functional diversification in ligand transport. Here, we combine phylogenetic analysis to profile SLC25 transporters across common eukaryotic model organisms, from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, to Homo sapiens, and assess their sequence adaptations to the transported ligands within individual subfamilies. Using several recently studied and poorly characterized SLC25 transporters, we discuss the potentials and limitations of phylogenetic analysis in guiding functional characterization.
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Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer.
Yang, X, Zhuang, J, Song, W, Shen, W, Wu, W, Shen, H, Han, S
Journal of cellular and molecular medicine. 2023;(7):906-919
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Abstract
The mitochondrial-associated membrane (MAM) is a physical platform that facilitates communication between the endoplasmic reticulum (ER) and mitochondria. It is enriched with many proteins and enzymes and plays an important role in the regulation of several fundamental physiological processes, such as calcium (Ca2+ ) transfer, lipid synthesis, cellular autophagy and ER stress. Accumulating evidence suggests that oncogenes and suppressor genes are present at the ER-mitochondrial contact site, and their alterations can affect Ca2+ flux, lipid homeostasis, and the dysregulation of mitochondrial dynamics, thereby influencing the fate of cancer cells. Understanding the fundamental role of MAM-resident proteins in tumorigenesis could support the search for novel therapeutic targets in cancer. In this review, we summarize the basic structure of MAM and the core functions of MAM-resident proteins in tumorigenesis. In addition, we discuss the mechanisms by which natural compounds promote cancer cell apoptosis from the perspective of ER stress.
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Effects of whey protein complex combined with low-intensity exercise in elderly inpatients with COPD at a stable stage.
Zong, M, Shen, H, Ren, L, Han, T, Chen, J, Chen, Y, Lu, J, Zhang, Y, Li, S, Sun, J
Asia Pacific journal of clinical nutrition. 2023;(4):375-382
Abstract
BACKGROUND AND OBJECTIVES Previous literature mostly has demonstrated the efficacy of pulmonary rehabilitation (PR) combined with whole nutrition powder in patients with chronic obstructive pulmonary disease (COPD). However, the benefits of whey protein as an oral nutritional supplement (ONS) during PR are not clear. METHODS AND STUDY DESIGN It took 12 weeks to complete the trial, we divided 90 elderly patients with stable-stage COPD into a low-intensity exercise group (n= 30, PR group), PR plus whey proteins complex group (n= 30, PRWP group), and a control group (n= 30) randomly, and assessed index such as exercise capacity, mental health status, lung function, and body composition. Eventually, 84 people persisted until the end of the trial. RESULTS Compared with the control group, hand grip strength (HGS)(1.4 ± 0.6 kg, and 1.0 ± 0.2 kg respectively, p< 0.05) in the PRWP and PR group, 6 minutes of walking distance (6MWD)(14.1 ± 3.8m, p< 0.05) in PRWP group improved. Furthermore, compared with the PR group, Medical Research Council Dyspnea Scale (MRC)(-0.2 ± 0.1, p< 0.01), anxiety score (-1.2 ± 0.4, p< 0.01), and body weight (2.0 ± 0.8kg, p< 0.05) improved in the PRWP group. There were no inter-group differences in a fat-free mass index or appendicular skeletal muscle mass index. CONCLUSIONS Muscle strength could be enhanced in both intervention models. Adding whey protein complex was additionally successful in rectifying dyspnea, anxiety, and weight loss caused by exercise. This rehabilitation pattern might be valuable in elderly patients with COPD.
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Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?
Zhang, H, Shen, H, Zhou, L, Xie, L, Kong, D, Wang, H
Cellular and molecular gastroenterology and hepatology. 2023;(4):809-819
Abstract
Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes that express the semi-invariant T cell receptor and recognize riboflavin metabolites via the major histocompatibility complex class I-related protein. Given the abundance of MAIT cells in the human body, their role in human diseases has been increasingly studied in recent years. MAIT cells may serve as targets for clinical therapy. Specifically, this review discusses how MAIT cells are altered in gastric, esophageal, intestinal, and hepatobiliary diseases and describes their protective or pathogenic roles. A greater understanding of MAIT cells will provide a more favorable therapeutic approach for digestive diseases in the clinical field.
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Precipitation Kinetics of Water-Cooled Copper Mold Al-Mg-Si(-Mn, Zr) Alloy during Aging.
Shen, H, Shi, J, Zhou, Y, Wang, X, Yao, G
Materials (Basel, Switzerland). 2023;(23)
Abstract
The aging precipitation behavior of 6061 aluminum alloy that underwent iron casting and water-cooled copper casting and 6061 aluminum with Mn and Zr elements added was studied. Firstly, the hardness curves, tensile properties, and fracture morphology of four aging alloys-6061 (iron mold casting), 6061 (water-cooled copper mold casting), 6061-0.15Mn-0.05Zr (iron mold casting), and 6061-0.15Mn-0.05Zr (water-cooled copper mold casting)-were studied. The results of the aging hardness curve show that the aging precipitated phase of the 6061 alloy cast with a water-cooled copper mold is dispersed. The addition of Mn increases the amount of coarse inclusion α-(AlMnFeSi) in the alloy, resulting in a decrease in the age hardening property. The addition of Zr is related to the nucleation and growth of the G.P. region in the early aging period, mainly changing the formation rate and quantity of the G.P. region, leading to the advancement of peak aging and an increase in hardness. After the G.P. region gradually transforms into the β phase, the hardness of the alloy increases with the increase in the volume fraction of the β phase. When the β″ phase is coarsened to the point where the fault line can be bypassed, the transitional metastable β' phase begins to precipitate, and the coherent distortion around it weakens, indicating over-aging. Finally, the equilibrium phase Mg2Si is formed. The results of the tensile tests indicate that the tensile strength and yield strength of the 6061-0.15Mn-0.05Zr alloy produced by water-cooled copper casting after aging are 356 Mpa and 230 Mpa, respectively. These values are 80 MPa and 75 MPa higher, respectively, than those of the 6061 aluminum alloy produced via iron casting. However, the elongation is by 5%. The fracture morphology of the tensile sample of the aging alloy shows that dislocation slip in the alloy results in dislocation plugging, stress concentration, and the initiation of crack cleavage on the surface. The fracture of the water-cooled copper mold-casting alloy is a ductile fracture of the microporous aggregation type, and the macroscopic fracture exhibits an obvious "neck shrinkage" phenomenon. The fracture analysis is consistent with the mechanical properties. The DSC curve shows that there is no enrichment process of solute atoms during the heating process, and the aging precipitation process after homogenization is as follows: G.P. zone → β″ phase → β' phase. The aging precipitation process of the water-cooled copper casting alloy after homogenization treatment is as follows: β″ phase → β' phase (no precipitation in the G.P. zone was observed). The results of the differential scanning calorimetry (DSC) analysis show that the main strengthening phase in the experimental alloy system is the β″ phase. The activation energies for the β″ phase precipitation were calculated and found to be 147 KJ/mol, 217 KJ/mol, 185 KJ/mol, and 235 KJ/mol, respectively. Additionally, a kinetic equation for the β″ phase precipitation during alloy aging was fitted.