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1.
Animals (Basel) ; 14(14)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39061518

ABSTRACT

Methane emissions from ruminants significantly contribute to greenhouse gases. This study explores the methane mitigation effect and mechanism of S. mcclurei through in vitro rumen fermentation, aiming to establish its potential as a feed additive. We investigated the effects of freeze-dried and dried S. mcclurei at supplementation levels of 2%, 5%, and 10% of dry matter on nutrient degradation, ruminal fermentation, methane inhibition, and microbial community structure in in vitro rumen fermentation. The freeze-dried S. mcclurei at 2% supplementation significantly reduced CH4 emissions by 18.85% and enhanced crude protein degradability. However, total VFA and acetate concentrations were lower in both treatments compared to the control. The microbial shifts included a decrease in Lachnospiraceae_NK3A20_group and Ruminococcus and an increase in Selenomonas, Succinivibrio, and Saccharofermentans, promoting propionate production. Additionally, a significant reduction in Methanomicrobium was observed, indicating direct methane mitigation. Freeze-dried S. mcclurei at a 2% supplementation level shows potential as an effective methane mitigation strategy with minimal impact on rumen fermentation, supported by detailed insights into microbial community changes.

2.
Antonie Van Leeuwenhoek ; 117(1): 108, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080041

ABSTRACT

A novel rod-shaped bacterium, designated as strain SYSU D60015T that formed yellowish colonies was isolated from a sandy soil collected from the Kumtag Desert in Xinjiang, China. Cells were Gram-stain-negative, oxidase-positive, catalase-negative and motile with a single polar flagellum. Growth optimum occurred between 28 and 37 °C, pH 7.0 and with 0-0.5% (W/V) NaCl. The predominant cellular fatty acids (> 5%) were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C19:0 cyclo ω8c, C18:1 ω7c 11-methyl and C16:0. The polar lipid profile contained one phosphatidylethanolamine, one diphosphatidylglycerol, one phosphatidylglycerol, one unidentified phospholipid, three unidentified aminolipids, two unidentified aminophospholipids and seven unidentified lipids. The only respiratory quinone was ubiquinone-10. Based on 16S rRNA gene sequence phylogenetic analysis, strain SYSU D60015T was found to form a distinct linage within the family Sneathiellaceae, and had 16S rRNA gene sequence similarities of 90.8% to Taonella mepensis H1T, and 90.2% to Ferrovibrio denitrificans S3T. The genome of SYSU D60015T was 5.66 Mb in size with 68.2% of DNA G + C content. The low digital DNA-DNA hybridization (dDDH, 18.0%), average nucleotide identity (ANI, 77.5%) and amino acid identity (AAI, 56.0%) values between SYSU D60015T and Ferrovibrio terrae K5T indicated that SYSU D60015T might represent a distinct genus. Based on the phylogenetic, phenotypic, chemotaxonomic and genomic data, we propose Desertibaculum subflavum gen. nov., sp. nov. as a novel species of a new genus within the family Sneathiellaceae. The type strain is SYSU D60015T (= NBRC 112952T = CGMCC 1.16256T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Soil Microbiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , China , Fatty Acids/analysis , Fatty Acids/chemistry , Sequence Analysis, DNA , Phospholipids/analysis , Phospholipids/chemistry
3.
Heliyon ; 10(12): e33452, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39027429

ABSTRACT

Ion channels are widely present in cell membranes, serving as crucial pathways for the movement of ions enter and exit cells. Variations in the expression of ion channels are crucial for regulating cellular functions. Among the genes associated with leukemia, certain genes encode ion channels. When these ion channels experience dysfunction or changes in expression, they can impact the physiological functions and signal transduction of hematopoietic cells, thereby regulating leukemia cell proliferation, differentiation, invasion/migration, and apoptosis. This article will provide a comprehensive review of the research progress on the expression and function of various ion channels in leukemia, thoroughly exploring their roles and mechanisms in the onset and progression of the disease, providing new insights and ideas for identifying potential biomarkers and developing new treatment methods for leukemia, thereby promoting innovations in future leukemia diagnosis and therapy.

4.
J Comput Biol ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39047029

ABSTRACT

High-throughput chromosome conformation capture (Hi-C) technology captures spatial interactions of DNA sequences into matrices, and software tools are developed to identify topologically associating domains (TADs) from the Hi-C matrices. With structural information theory, SuperTAD adopted a dynamic programming approach to find the TAD hierarchy with minimal structural entropy. However, the algorithm suffers from high time complexity. To accelerate this algorithm, we design and implement an approximation algorithm with a theoretical performance guarantee. We implemented a package, SuperTAD-Fast. Using Hi-C matrices and simulated data, we demonstrated that SuperTAD-Fast achieved great runtime improvement compared with SuperTAD. SuperTAD-Fast shows high consistency and significant enrichment of structural proteins from Hi-C data of human cell lines in comparison with the existing six hierarchical TADs detecting methods.

5.
Reprod Toxicol ; 129: 108671, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038764

ABSTRACT

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5 % O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

6.
Chem Sci ; 15(29): 11347-11357, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39055007

ABSTRACT

Rational design of small organic molecule-based NIR-II photosensitizers (PSs) with high singlet oxygen quantum yield in aqueous solution for deep tissue imaging and cancer therapy still presents challenges. Herein, we devised a general synthesis strategy to obtain six NIR-II region PSs with tunable aggregation states by adjusting the steric effect, and all PSs possess longer NIR absorption/emission wavelengths with tails extending beyond 1200 nm. Notably, ATX-6 possessed a singlet oxygen quantum yield of 38.2% and exhibited concentration-dependent J-aggregation properties upon self-assembly in an aqueous solution. What's more, supramolecular engineering with DSPE-PEG2000 further enhanced its degree of J-aggregation, which was attributed to the dimer-excited reduction of the energy levels of the single-linear/triple-linear states and the facilitation of intersystem crossover processes. In addition, ATX-6 NPs showed superior photodynamic therapy effects and great potential in high-contrast in vivo bioimaging of the NIR-II region. These results provide valuable insights for achieving the diagnostic and therapeutic integration of tumors.

7.
Environ Pollut ; 359: 124557, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39019306

ABSTRACT

The ecological impact of emerging contaminants (ECs) in aquatic environments has raised concerns, particularly with regards to urine as a significant source of such contaminants in wastewater. The current investigation used the UV/Peracetic Acid (UV/PAA) processes, an innovative advanced oxidation technology, to effectively separate two emerging pollutants from urine at its source, namely, ciprofloxacin (CIP) and bisphenol A(BPA). The research findings demonstrate that the presence of the majority of characteristic ions has minimal impact on the degradation of ECs. However, in synthetic hydrolyzed urine, only NH4+ inhibits the degradation of two types of ECs, with a more pronounced effect observed on CIP degradation compared to BPA.The impact of halogen ions, specifically Cl- and I-, on the degradation of CIP in synthetic hydrolyzed urine was a complex phenomenon. When these two halogen ions are present individually, the generation of reactive halogen species (RHS) within the system enhances the degradation of CIP. However, when both types of ions coexist, the formation of diatomic radical species partially inhibits degradation. In terms of BPA degradation, while the production of reactive chlorine species (RCS) to some extent hinders the reaction rate, the generation of reactive iodine species (RIS) promotes the overall process. CIP undergoes fragmentation of the piperazine and quinoline rings, decarboxylation, defluorination reactions, as well as substitution reactions, leading to the formation of products with simplified structures. The degradation of BPA occurs gradually through hydroxyl and halogen substitution as well as isopropyl cleavage. The preliminary toxicity analysis confirmed that the presence of halogen ions in urine resulted in the formation of halogenated products in two types of ECs, albeit with an overall reduction in toxicity. The UV/PAA processes was considered to be an effective and relatively safe approach for the separation of ECs in urine.

8.
Article in English | MEDLINE | ID: mdl-39037442

ABSTRACT

Two Gram-stain-negative, aerobic, milk-white coloured, non-motile, short rod-shaped bacteria, designated as strains SYSU D60010T and SYSU D60012T, were isolated from sand samples collected from the Taklimakan Desert of Xinjiang Province in China. Both strains were positive for oxidase, catalase and nitrate reduction, but negative for amylase, H2S production, hydrolysis of gelatin and cellulase. Strains SYSU D60010T and SYSU D60012T grew well at 28 °C, at pH 7 and had the same NaCl tolerance range of 0-1 % (w/v). The major fatty acids (>5 %) of strains SYSU D60010T and SYSU D60012T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), iso-C19 : 0 cyclo ω8c, C16 : 0 and iso-C18 : 1 2-OH. Q-10 was the only respiratory ubiquinone. Strains SYSU D60010T and SYSU D60012T showed high 16S rRNA gene sequence similarities to Aestuariivirga litoralis SYSU M10001T (94.2 and 94.1 %), Rhodoligotrophos jinshengii BUT-3T (92.0 and 91.9 %) and Rhodoligotrophos appendicifer 120-1T (91.8 and 91.7 %), and the genomes were 7.4 and 5.8 Mbp in size with DNA G+C contents of 62.8 and 63.0 mol%, respectively. Phylogenetic, phenotypic and chemotaxonomic characteristics indicated that these two strains represent a novel genus and two novel species within the family Aestuariivirgaceae. We propose the name Taklimakanibacter deserti gen. nov., sp. nov. for strain SYSU D60010T, representing the type strain of this species (=KCTC 52783T =NBRC 113344T) and Taklimakanibacter lacteus gen. nov., sp. nov. for strain SYSU D60012T, representing the type strain of this species (=KCTC 52785T=NBRC 113128T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Soil Microbiology , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , DNA, Bacterial/genetics , China , Ubiquinone/analogs & derivatives , Sand/microbiology
9.
Pest Manag Sci ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39031631

ABSTRACT

BACKGROUND: N6-Methyladenosine (m6A) is a common messenger RNA (mRNA) modification that affects various physiological processes in stress responses. However, the role of m6A modifications in plants responses to herbivore stress remains unclear. RESULTS: Here, we found that an infestation of brown planthopper (Nilaparvata lugens) female adults enhanced the resistance of rice to N. lugens. The m6A methylome analysis of N. lugens-infested and uninfested rice samples was performed to explore the interaction between rice and N. lugens. The m6A methylation mainly occurred in genes that were actively expressed in rice following N. lugens infestation, while an analysis of the whole-genomic mRNA distribution of m6A showed that N. lugens infestation caused an overall decrease in the number of m6A methylation sites across the chromosomes. The m6A methylation of genes involved in the m6A modification machinery and several defense-related phytohormones (jasmonic acid and salicylic acid) pathways was increased in N. lugens-infested rice compared to that in uninfested rice. In contrast, m6A modification levels of growth-related phytohormone (auxin and gibberellin) biosynthesis-related genes were significantly attenuated during N. lugens infestation, accompanied by the down-regulated expression of these transcripts, indicating that rice growth was restricted during N. lugens attack to rapidly optimize resource allocation for plant defense. Integrative analysis of the differential patterns of m6A methylation and the corresponding transcripts showed a positive correlation between m6A methylation and transcriptional regulation. CONCLUSION: The m6A modification is an important strategy for regulating the expression of genes involved in rice defense and growth during rice-N. lugens interactions. These findings provide new ideas for formulating strategies to control herbivorous pests. © 2024 Society of Chemical Industry.

10.
Article in English | MEDLINE | ID: mdl-38979770

ABSTRACT

Thallium (Tl), though not essential for biological systems, is widely used in industrial activities, resulting in soil pollution and adverse effects on soil biota. Systematic toxicological studies on Tl, especially concerning soil organisms, are relatively rare. This research evaluates the toxic effects of Tl on earthworms by measuring oxidative stress biomarkers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), and by assessing the expression of functional genes, such as heat shock protein 70 (Hsp70), metallothionein (MT), and annetocin (ANN). Additionally, this study employs the Biomarker Response Index (BRI) and two-way ANOVA to comprehensively assess the cumulative toxicity of Tl in earthworms. The findings indicate that Tl exposure significantly exacerbates oxidative stress and cellular damage in earthworms, particularly under conditions of high concentration and prolonged exposure. BRI results demonstrate a continuous decline in the physiological state of earthworms with increasing Tl concentration and exposure duration. Two-way ANOVA reveals significant dose-responsive increases in SOD and CAT activities, as well as in ANN gene expression. Apart from GST activity, other biomarkers significantly increased over time, and the changes in biomarkers such as SOD, CAT, MDA, and 8-OHdG were significantly influenced by dose and time. LSD post hoc tests show significant effects of dose, time, and their interactions on all biomarkers except for GST. These findings are valuable for gaining a deeper understanding of the ecological risks of Tl in soil environments and its potential threats to soil biota, aiding in the management of ecological risks associated with Tl-contaminated soils.

11.
J Phys Chem A ; 128(28): 5516-5524, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38954640

ABSTRACT

Machine learning is capable of effectively predicting the potential energies of molecules in the presence of high-quality data sets. Its application in the construction of ground- and excited-state potential energy surfaces is attractive to accelerate nonadiabatic molecular dynamics simulations of photochemical reactions. Because of the huge computational cost of excited-state electronic structure calculations, the construction of a high-quality data set becomes a bottleneck. In the present work, we first built two data sets. One was obtained from surface hopping dynamics simulations at the semiempirical OM2/MRCI level. Another was extracted from the dynamics trajectories at the CASSCF level, which was reported previously. The ground- and excited-state potential energy surfaces of ethylene-bridged azobenzene at the CASSCF computational level were constructed based on the former low-level data set. Although non-neural network machine learning methods can achieve good or modest performance during the training process, only neural network models provide reliable predictions on the latter external test data set. The BPNN and SchNet combined with the Δ-ML scheme and the force term in the loss functions are recommended for dynamics simulations. Then, we performed excited-state dynamics simulations of the photoisomerization of ethylene-bridged azobenzene on machine learning potential energy surfaces. Compared with the lifetimes of the first excited state (S1) estimated at different computational levels, our results on the E isomer are in good agreement with the high-level estimation. However, the overestimation of the Z isomer is unimproved. It suggests that smaller errors during the training process do not necessarily translate to more accurate predictions on high-level potential energies or better performance on nonadiabatic dynamics simulations, at least in the present case.

12.
Bioinformatics ; 40(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950175

ABSTRACT

MOTIVATION: T cell receptors (TCRs) constitute a major component of our adaptive immune system, governing the recognition and response to internal and external antigens. Studying the TCR diversity via sequencing technology is critical for a deeper understanding of immune dynamics. However, library sizes differ substantially across samples, hindering the accurate estimation/comparisons of alpha diversities. To address this, researchers frequently use an overall rarefying approach in which all samples are sub-sampled to an even depth. Despite its pervasive application, its efficacy has never been rigorously assessed. RESULTS: In this paper, we develop an innovative "multi-bin" rarefying approach that partitions samples into multiple bins according to their library sizes, conducts rarefying within each bin for alpha diversity calculations, and performs meta-analysis across bins. Extensive simulations using real-world data highlight the inadequacy of the overall rarefying approach in controlling the confounding effect of library size. Our method proves robust in addressing library size confounding, outperforming competing normalization strategies by achieving better-controlled type-I error rates and enhanced statistical power in association tests. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/mli171/MultibinAlpha. The datasets are freely available at https://doi.org/10.21417/B7001Z and https://doi.org/10.21417/AR2019NC.


Subject(s)
Receptors, Antigen, T-Cell , Receptors, Antigen, T-Cell/genetics , Humans , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods , Gene Library , Genetic Variation
13.
J Urol ; : 101097JU0000000000004129, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950376

ABSTRACT

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.

14.
Antonie Van Leeuwenhoek ; 117(1): 98, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981868

ABSTRACT

An aerobic, Gram-stain-negative bacterium, designated as SYSU D00382T, was sourced from soil of Gurbantunggut Desert, PR China. The strain was short-rod-shaped, oxidase-positive and catalase-negative, with yellow-colored, convex, round, and smooth colonies on TSA plate. Growth and proliferation occurred at 4-37 °C (optimal: 28-30 °C), pH 5.0-8.0 (optimal: pH 6.0-7.0) and NaCl concentration of 0-2.5% (optimal: 0-0.5%). The 16S rRNA gene based phylogenetic assessment showed that SYSU D00382T belonged to the genus Pedobacter, and was most closely related to Pedobacter ginsengisoli Gsoil 104T with similarity of 97.7%. The genomic DNA G+C content of SYSU D00382T was 46.4%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00382T and P. ginsengisoli Gsoil 104T were 75.7% and 17.5%, respectively. The main polar lipid was phosphatidylethanolamine. The major fatty acids (> 5%) were iso-C15:0, iso-C17:0 3-OH, summed features 3 and 9. The sole respiratory quinone identified was MK-7. The phylogeny based on 16S rRNA gene and whole-genome sequences revealed that SYSU D00382T formed a robust lineage with P. ginsengisoli Gsoil 104T. Based on phenotypic, phylogenetic and genotypic data, a novel specie named Pedobacter deserti sp. nov. is proposed. The type strain is SYSU D00382T (= CGMCC 1.18627T = MCCC 1K04972T = KCTC 82279T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Soil Microbiology , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Pedobacter/physiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , China , Nucleic Acid Hybridization , Sequence Analysis, DNA
15.
Heliyon ; 10(13): e33938, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071710

ABSTRACT

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an 'inside-out' growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3'UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3'UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the 'inside-out' growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

17.
iScience ; 27(6): 109908, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38827397

ABSTRACT

Accurate detection of pathogens, particularly distinguishing between Gram-positive and Gram-negative bacteria, could improve disease treatment. Host gene expression can capture the immune system's response to infections caused by various pathogens. Here, we present a deep neural network model, bvnGPS2, which incorporates the attention mechanism based on a large-scale integrated host transcriptome dataset to precisely identify Gram-positive and Gram-negative bacterial infections as well as viral infections. We performed analysis of 4,949 blood samples across 40 cohorts from 10 countries using our previously designed omics data integration method, iPAGE, to select discriminant gene pairs and train the bvnGPS2. The performance of the model was evaluated on six independent cohorts comprising 374 samples. Overall, our deep neural network model shows robust capability to accurately identify specific infections, paving the way for precise medicine strategies in infection treatment and potentially also for identifying subtypes of other diseases.

18.
Insect Sci ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831720

ABSTRACT

N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.

19.
Chemistry ; : e202400985, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38932665

ABSTRACT

Bioreduction of spin labels and polarizing agents (generally stable radicals) has been an obstacle limiting the in-cell applications of pulsed electron paramagnetic resonance (EPR) spectroscopy and dynamic nuclear polarization (DNP). In this work, we have demonstrated that two semiquinone methide radicals (OXQM• and CTQM•) can be easily produced from the trityl-based quinone methides (OXQM and CTQM) via reduction by various reducing agents including biothiols and ascorbate under anaerobic conditions. Both radicals have relatively low pKa's and exhibit EPR single line signals at physiological pH. Moreover, the bioreduction of OXQM in three cell lysates enables quantitative generation of OXQM• which was most likely mediated by flavoenzymes. Importantly, the resulting OXQM• exhibited extremely high stability in the E.coli lysate under anaerobic conditions with 76- and 14.3-fold slower decay kinetics as compared to the trityl OX063 and a gem-diethyl pyrrolidine nitroxide. Intracellular delivery of OXQM into HeLa cells was also achieved by covalent conjugation with a cell-permeable peptide as evidenced by the stable intracellular EPR signal from the OXQM• moiety. Owing to extremely high resistance of OXQM• towards bioreduction, OXQM and its derivatives show great application potential in in-cell EPR and in-cell DNP studies for various cells which can endure short-term anoxic treatments.

20.
Sci Rep ; 14(1): 13906, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886545

ABSTRACT

Colon adenocarcinoma (COAD) is the second leading cause of cancer death, and there is still a lack of diagnostic biomarkers and therapeutic targets. In this study, bioinformatics analysis of the TCGA database was used to obtain RUNX1, a gene with prognostic value in COAD. RUNX1 plays an important role in many malignancies, and its molecular regulatory mechanisms in COAD remain to be fully understood. To explore the physiological role of RUNX1, we performed functional analyses, such as CCK-8, colony formation and migration assays. In addition, we investigated the underlying mechanisms using transcriptome sequencing and chromatin immunoprecipitation assays. RUNX1 is highly expressed in COAD patients and significantly correlates with survival. Silencing of RUNX1 significantly slowed down the proliferation and migratory capacity of COAD cells. Furthermore, we demonstrate that CDC20 and MCM2 may be target genes of RUNX1, and that RUNX1 may be physically linked to the deubiquitinating enzyme USP31, which mediates the upregulation of RUNX1 protein to promote transcriptional function. Our results may provide new insights into the mechanism of action of RUNX1 in COAD and reveal potential therapeutic targets for this disease.


Subject(s)
Cdc20 Proteins , Core Binding Factor Alpha 2 Subunit , Gene Expression Regulation, Neoplastic , Minichromosome Maintenance Complex Component 2 , Ubiquitination , Humans , Core Binding Factor Alpha 2 Subunit/metabolism , Core Binding Factor Alpha 2 Subunit/genetics , Cdc20 Proteins/metabolism , Cdc20 Proteins/genetics , Minichromosome Maintenance Complex Component 2/metabolism , Minichromosome Maintenance Complex Component 2/genetics , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Cell Proliferation/genetics , Ubiquitin-Specific Proteases/metabolism , Ubiquitin-Specific Proteases/genetics , Disease Progression , Cell Movement/genetics
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