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1.
Eur Radiol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844619

ABSTRACT

OBJECTIVES: Despite some existing studies on the safety of high static magnetic fields (SMFs), the effects of ultra-high SMFs above 20.0 T for embryonic development in early pregnancy are absent. The objective of this study is to evaluate the influence of 16.8-22.0 T SMF on the development of zebrafish embryos, which will provide important information for the future application of ultra-high field magnetic resonance imaging (MRI). METHODS: Two-hour exposure to homogenous (0 T/m) 22.0 T SMF, or 16.8 T SMFs with 123.25 T/m spatial gradient of opposite magnetic force directions was examined in the embryonic development of 200 zebrafish. Their body length, heart rate, spontaneous tail-wagging movement, hatching and survival rate, photomotor response, and visual motor response (VMR) were analyzed. RESULTS: Our results show that these ultra-high SMFs did not significantly affect the general development of zebrafish embryos, such as the body length or spontaneous tail-wagging movement. However, the hatching rate was reduced by the gradient SMFs (p < 0.05), but not the homogenous 22.0 T SMF. Moreover, although the zebrafish larva activities were differentially affected by these ultra-high SMFs (p < 0.05), the expression of several visual and neurodevelopmental genes (p < 0.05) was generally downregulated in the eyeball. CONCLUSIONS: Our findings suggest that exposure to ultra-high SMFs, especially the gradient SMFs, may have adverse effects on embryonic development, which should cause some attention to the future application of ultra-high field MRIs. CLINICAL RELEVANCE STATEMENT: As technology advances, it is conceivable that very strong magnetic fields may be adapted for use in medical imaging. Possible dangers associated with these higher Tesla fields need to be considered and evaluated prior to human use. KEY POINTS: Ultra-High static magnetic field may affect early embryonic development. High strength gradient static magnetic field exposure impacted zebrafish embryonic development. The application of very strong magnetic fields for MR technologies needs to be carefully evaluated.

2.
Comput Struct Biotechnol J ; 23: 1877-1885, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38707542

ABSTRACT

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

3.
Article in English | MEDLINE | ID: mdl-38717638

ABSTRACT

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

4.
Heliyon ; 10(10): e31314, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813209

ABSTRACT

Bone nonunion is a common and serious orthopedic disorder, the occurrence of which is associated with a disruption of the dynamic balance between osteoblasts and osteoclasts during bone repair. However, the critical molecular mechanisms affecting this homeostasis are not well understood, and it is essential to investigate the specific components of this mechanism and to restore the balance between osteoblasts and osteoclasts to promote bone repair. First, we defined this complex local environmental factor as the "bone nonunion microenvironment" and identified the importance of the "struggle" between osteoblasts and osteoclasts, which is the most essential element in determining the process of repair. On this basis, we also explored the cellular factors that influence osteogenesis and the molecular signals that influence the balance between osteoclast and osteoblasts, which are important for restoring homeostasis. Further, we explored other factors involved in osteogenesis, such as the biomechanical environment, the nutritional environment, the acid-base environment, and the temperature environment, which are important players in osteogenesis. In conclusion, we found that the balance between osteoblasts and osteoclasts is the essence of bone healing, which is based on the "bone nonunion microenvironment". Therefore, investigating the role of the bone nonunion microenvironment in the system of osteoblast-osteoclast "struggle" provides an important basis for further understanding of the mechanism of nonunion and the development of new therapeutic approaches.

5.
Heliyon ; 10(9): e29914, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38737285

ABSTRACT

This study was based on the use of whole-genome DNA methylation sequencing technology to identify DNA methylation biomarkers in tumor tissue that can predict the prognosis of patients with pancreatic cancer (PCa). TCGA database was used to download PCa-related DNA methylation and transcriptome atlas data. Methylation driver genes (MDGs) were obtained using the MethylMix package. Candidate genes in the MDGs were screened for prognostic relevance to PCa patients by univariate Cox analysis, and a prognostic risk score model was constructed based on the key MDGs. ROC curve analysis was performed to assess the accuracy of the prognostic risk score model. The effects of PIK3C2B knockdown on malignant phenotypes of PCa cells were investigated in vitro. A total of 2737 differentially expressed genes were identified, with 649 upregulated and 2088 downregulated, using 178 PCa samples and 171 normal samples. MethylMix was employed to identify 71 methylation-driven genes (47 hypermethylated and 24 hypomethylated) from 185 TCGA PCa samples. Cox regression analyses identified eight key MDGs (LEF1, ZIC3, VAV3, TBC1D4, FABP4, MAP3K5, PIK3C2B, IGF1R) associated with prognosis in PCa. Seven of them were hypermethylated, while PIK3C2B was hypomethylated. A prognostic risk prediction model was constructed based on the eight key MDGs, which was found to accurately predict the prognosis of PCa patients. In addition, the malignant phenotypes of PANC-1 cells were decreased after the knockdown of PIK3C2B. Therefore, the prognostic risk prediction model based on the eight key MDGs could accurately predict the prognosis of PCa patients.

6.
Sci Total Environ ; 934: 173251, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38750731

ABSTRACT

Citizen scientist-based environmental monitoring and public education are becoming increasingly popular. However, current technologies for antibiotic-based novel contaminant identification are still restricted to laboratory sample collection and analysis due to detection methodologies and apparatus limitations. This study developed a time-resolved immunofluorescence-based simultaneous field-based assay for ciprofloxacin (CIP) and enrofloxacin (ENR) that matches test results to geographic locations. The assay helps the public understand the potential levels of antibiotic exposures in their environments and helps them take appropriate action to reduce risk. The assay was developed using smartphones and social software in addition to rapid testing. The method uses a portable, low-cost analytical kit with a smartphone app to build a field-based detection platform for the detection and analysis of ENR and CIP in water and aquatic products. The methodological evaluation was good, with detection limits of 0.4 ng/mL and 0.5 ng/g for ENR in water and fish, and quantification limits of 1.2 ng/mL and 1.4 ng/g, with recoveries of 89.0 %-101.0 % and 78.0 %-97.0 %. For CIP in water and fish, the limits of detection were 0.3 ng/mL and 0.4 ng/g, the limits of quantification were 0.9 ng/mL and 1.2 ng/g, and the recoveries were 75.0 %-91.0 % and 72.0 %-89.0 %, both with coefficients of variation <15 %. These limits were sufficient to prevent the two antibiotics from crossing over during simultaneous detection. The assay was validated using real samples to assess the effectiveness of the assay platform in field deployments, and the results were consistent with those obtained through liquid chromatography-tandem mass spectrometry (LC-MS) and enzyme-linked immunoassay (ELISA) techniques. In addition, the TRFIA assay process requires less time, uses more portable instruments, and is less complex than traditional methods. This study provides a new scientific, accurate, and rapid detection method for antibiotic detection by citizen scientists, helping scientists to obtain a wider range of data and providing more opportunities to solve scientific problems.


Subject(s)
Anti-Bacterial Agents , Citizen Science , Enrofloxacin , Environmental Monitoring , Water Pollutants, Chemical , Anti-Bacterial Agents/analysis , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Enrofloxacin/analysis , Ciprofloxacin/analysis , Smartphone , Fluorescent Antibody Technique/methods
7.
Sci Total Environ ; 935: 173017, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38719054

ABSTRACT

Carriers have been extensively employed to enhance nitrification performance during low-strength wastewater treatment by retaining slow-growing ammonia oxidizing microorganisms (AOMs). Still, there is a dearth of systematic understanding of biofilm properties and microbial community structure formed on different carriers. In this study, hydrophilic polyurethane foam (PUF) carriers were prepared and compared with five widely used commercial carriers, namely Kaldness 3, Biochip, activated carbon, volcanic rock, and zeolite. The results indicated that the biofilms formed on carriers enhanced microbial ammonia oxidation activity. Additionally, the biofilm developed on the PUF demonstrated the most superior performance among all selected carriers, not only exhibiting the highest abundant and the most active AOMs, with amoA gene abundance of 1.41 × 1013 copies/m3 and specific ammonia oxidation rate of 9.84 g NH4+-N/(m3 × h), but also possessing a compact structure, with 3.41 kg VSS/m3 and 46.83 mg extracellular polymeric substances/g VSS. The high-throughput sequencing analysis revealed that the comammox (CMX) Nitrospira dominated on biofilm due to the intrinsically low apparent half-saturation constant for substrate. A unique ecological community structure was established on PUF, characterized by low species diversity and high homogeneity in alignment with community characteristics of CMX. The biofilms on PUF contributed to the proliferation of CMX Nitrospira dominated by Nitrospira nitrosa, achieving the highest proportion among colonial three AOMs at 86.58 %. The appropriate average pore size, superior hydrophilicity, and large specific surface area of PUF carriers provided a robust foundation for the exceptional ammonia oxidation performance of the formed biofilms.


Subject(s)
Ammonia , Biofilms , Oxidation-Reduction , Polyurethanes , Waste Disposal, Fluid , Wastewater , Ammonia/metabolism , Waste Disposal, Fluid/methods , Wastewater/chemistry , Wastewater/microbiology , Hydrophobic and Hydrophilic Interactions , Nitrification
8.
Chemosphere ; 359: 142304, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38734253

ABSTRACT

Toxic organic and heavy metal contaminants commonly exist in industrial waste stream(s) and treatment is of great challenge. In this study, a dielectric barrier discharge (DBD) non-thermal plasma technology was employed for the simultaneous treatment of two important contaminants, chloramphenicol (CAP) and Cr(VI) in an aqueous solution through redox transformations. More than 70% of CAP and 20% of TOC were degraded in 60 min, while Cr(VI) was completely removed in 10 min. The hydroxyl radicals were the main active species for the degradation. Meanwhile, the consumption of hydroxyl radicals was beneficial to the reduction of Cr(VI). The synergistic effect was investigated between CAP degradation and Cr(VI) reduction. The reduction of Cr(VI) would be enhanced in the presence of CAP with a low concentration and could be inhibited under a high concentration, because part of hydroxyl radicals could be consumed by the low-concentration CAP and the obtained intermediates with a higher kinetic rate. However, CAP with a high concentration could react with such reductive species as eaq- and •H, which could compete with Cr(VI) and inhibit the reduction. In addition, the presence of Cr(VI) enhanced the degradation and mineralization of CAP; the study of obtained intermediates indicated that the presence of Cr(VI) changed the degradation path of CAP as Cr(VI) would react with reductive species, enhance the generation of hydroxyl radicals, and cause more hydroxylation reactions. Moreover, the mechanism for the simultaneous redox transformations of CAP and Cr(VI) was illustrated. This study indicates that the DBD non-thermal plasma technology can be one of better solutions for simultaneous elimination of heavy metal and organic contaminants in aquatic environments.


Subject(s)
Chloramphenicol , Chromium , Oxidation-Reduction , Water Pollutants, Chemical , Chloramphenicol/chemistry , Chromium/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Plasma Gases/chemistry , Hydroxyl Radical/chemistry , Waste Disposal, Fluid/methods
9.
Am J Prev Cardiol ; 18: 100668, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38646020

ABSTRACT

Objective: To evaluate whether and to what extent changes in cardiovascular health (CVH) based on life's essential 8 (LE8) are associated with incident cardiovascular disease (CVD). Methods: A total of 7,194 participants were derived from UK Biobank. CVH was evaluated using a modified version of LE8. Participants were classified into three groups according to their LE8 score: high CVH (LE8 score≥80), moderate CVH (50≤LE8 score<80), and low CVH (LE8 score<50). Changes in CVH between 2006/2010 and 2012/2013 were analyzed. Results: During a median of 10.3 years of follow-up, CVD was observed in 597 participants. Compared to the consistent moderate group, the moderate to low group was associated with about 128 % increased risk of CVD (Hazard ratio [HR]: 2.28; 95 % confidence interval [CI]: 1.61, 3.23), and the relevant HR (95 % CI) was 2.19 (1.46, 3.29) for the consistent low group; no statistically significant results were observed in the other groups. Moreover, no statistically significant exposure-response association between absolute change in LE8 score and incident CVD was documented (Poverall=0.15). Conclusion: Change in CVH based on LE8 was associated with the risk of CVD; however, the relationship varied widely in different CVH change patterns.

10.
Eur J Clin Invest ; : e14226, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632688

ABSTRACT

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes a heavy economic burden on people and society. Although it is well established that IVDD is associated with genetic susceptibility, ageing and obesity, its pathogenesis remains incompletely understood. Previously, IVDD was thought to occur because of excessive mechanical loading leading to destruction of nucleus pulposus cells (NPCs), but studies have shown that IVDD is a much more complex process associated with inflammation, metabolic factors and NPCs death and can involve all parts of the disc, characterized by causing NPCs death and extracellular matrix (ECM) degradation. The damage pattern of NPCs in IVDD is like that of some programmed cell death, suggesting that IVDD is associated with programmed cell death. Although apoptosis and pyroptosis of NPCs have been studied in IVDD, the pathogenesis of intervertebral disc degeneration can still not be fully elucidated by using only traditional cell death modalities. With increasing research, some new modes of cell death, PANoptosis, ferroptosis and senescence have been found to be closely related to intervertebral disc degeneration. Among these, PANoptosis combines essential elements of pyroptosis, apoptosis and necroptosis to form a highly coordinated and dynamically balanced programmed inflammatory cell death process. Furthermore, we believe that PANoptosis may also crosstalk with pyroptosis and senescence. Therefore, we review the progress of research on multiple deaths of NPCs in IVDD to provide guidance for clinical treatment.

11.
Stress Health ; : e3403, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38625789

ABSTRACT

This study aims to elucidate associations among self-compassion, depression, and suicidal ideation, particularly with respect to gender differences. Using a multigroup cross-lagged panel model, we conducted a longitudinal evaluation of 424 Chinese adolescents (55.85% boys; Mage = 18.02, SD = 0.73 at baseline). Our findings indicated that suicidal ideation at T1 positively predicted depression 6 months later, while negatively predicted self-compassion. However, self-compassion negatively predicted depression 6 months later, specifically in boys, but not in girls. Furthermore, self-compassion significantly mediated the relationship between suicidal ideation at T1 and depression at T2. This study helps to uncover the underlying relationships between self-compassion, depression, and suicidal ideation, and also provide a detailed insight into the differential effects of self-compassion on depression among boys and girls.

12.
RSC Adv ; 14(15): 10697-10702, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38567328

ABSTRACT

The microstructure and high conductivity properties of phosphorus-doped nanocrystalline silicon films were investigated on samples prepared by a plasma-enhanced chemical vapor deposition technique and the KrF pulsed excimer laser irradiation method. The results of Fourier transform infrared spectroscopy and Raman spectroscopy show that Si nanocrystallites with an average diameter of 2 nm to 3 nm are formed in the film. The degree of crystallinity increases with the increase of laser radiation intensity, while the content of hydrogen decreases gradually. More phosphorus atoms are substitutionally incorporated into the nc-Si dots under higher laser irradiation fluence, which is responsible for the high dark conductivity. By controlling the laser fluence at 1.0 J cm-2, the dark conductivity as high as 25.7 S cm-1 can be obtained. Based on the measurements of temperature-dependent conductivity, the carrier transport processes are discussed. The phosphorus doping and the increase of electron concentration are considered to be the reason for high dark conductivity and extremely low conductivity activation energy.

13.
iScience ; 27(4): 109605, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38633001

ABSTRACT

Supporting healthy pregnancy outcomes requires a comprehensive understanding of the molecular and cellular programs of peri-implantation development, when most pregnancy failure occurs. Here, we present single-cell transcriptomes of bovine peri-implantation embryo development at day 12, 14, 16, and 18 post-fertilization. We defined the cellular composition and gene expression of embryonic disc, hypoblast, and trophoblast lineages in bovine peri-implantation embryos, and identified markers and pathway signaling that represent distinct stages of bovine peri-implantation lineages; the expression of selected markers was validated in peri-implantation embryos. Using detailed time-course transcriptomic analyses, we revealed a previously unrecognized primitive trophoblast cell lineage. We also characterized conserved and divergence peri-implantation lineage programs between bovine and other mammalian species. Finally, we established cell-cell communication signaling underlies embryonic and extraembryonic cell interaction to ensure proper early development. These data provide foundational information to discover essential biological signaling underpinning bovine peri-implantation development.

14.
Zool Res ; 45(3): 478-491, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38682430

ABSTRACT

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.


Subject(s)
Acetaminophen , Analgesics, Non-Narcotic , Chemical and Drug Induced Liver Injury , Drug Overdose , Acetaminophen/toxicity , Animals , Mice , Analgesics, Non-Narcotic/toxicity , Oxidative Stress/drug effects , Male , Magnetic Fields , Acetylcysteine/therapeutic use , Acetylcysteine/pharmacology
15.
Ecotoxicol Environ Saf ; 276: 116311, 2024 May.
Article in English | MEDLINE | ID: mdl-38615639

ABSTRACT

Prenatal environmental exposure could be an essential health risk factor associated with neurodevelopmental disorders in offspring. However, the exact mechanisms underlying the impact of prenatal PM2.5 exposure on offspring cognition remain unclear. In our recent study using a PM2.5 exposed pregnant mouse model, we observed significant synaptic dysfunction in the hippocampi of the offspring. Concurrently, the epigenetic regulator of KDM5A and the Shh signaling pathway exhibited decreased activities. Significantly, changes in hippocampal KDM5A and Shh levels directly correlated with PM2.5 exposure intensity. Subsequent experiments revealed a marked reduction in the expression of Shh signaling and related synaptic proteins when KDM5A was silenced in cells. Notably, the effects of KDM5A deficiency were reversed significantly with the supplementation of a Shh activator. Furthermore, our findings indicate that Shh activation significantly attenuates PM2.5-induced synaptic impairments in hippocampal neurons. We further demonstrated that EGR1, a transcriptional inhibitor, plays a direct role in KDM5A's regulation of the Shh pathway under conditions of PM2.5 exposure. Our results suggest that the KDM5A's inhibitory regulation on the Shh pathway through the EGR1 gene is a crucial epigenetic mechanism underlying the synaptic dysfunction in hippocampal neurons caused by maternal PM2.5 exposure. This emphasizes the role of epigenetic regulations in neurodevelopmental disorders caused by environmental factors.


Subject(s)
Epigenesis, Genetic , Hedgehog Proteins , Hippocampus , Particulate Matter , Prenatal Exposure Delayed Effects , Signal Transduction , Hippocampus/drug effects , Animals , Female , Pregnancy , Signal Transduction/drug effects , Epigenesis, Genetic/drug effects , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Mice , Particulate Matter/toxicity , Retinoblastoma-Binding Protein 2/genetics , Maternal Exposure/adverse effects , Synapses/drug effects , Air Pollutants/toxicity
16.
J Cell Mol Med ; 28(9): e18298, 2024 May.
Article in English | MEDLINE | ID: mdl-38683133

ABSTRACT

Precise and personalized drug application is crucial in the clinical treatment of complex diseases. Although neural networks offer a new approach to improving drug strategies, their internal structure is difficult to interpret. Here, we propose PBAC (Pathway-Based Attention Convolution neural network), which integrates a deep learning framework and attention mechanism to address the complex biological pathway information, thereby provide a biology function-based robust drug responsiveness prediction model. PBAC has four layers: gene-pathway layer, attention layer, convolution layer and fully connected layer. PBAC improves the performance of predicting drug responsiveness by focusing on important pathways, helping us understand the mechanism of drug action in diseases. We validated the PBAC model using data from four chemotherapy drugs (Bortezomib, Cisplatin, Docetaxel and Paclitaxel) and 11 immunotherapy datasets. In the majority of datasets, PBAC exhibits superior performance compared to traditional machine learning methods and other research approaches (area under curve = 0.81, the area under the precision-recall curve = 0.73). Using PBAC attention layer output, we identified some pathways as potential core cancer regulators, providing good interpretability for drug treatment prediction. In summary, we presented PBAC, a powerful tool to predict drug responsiveness based on the biology pathway information and explore the potential cancer-driving pathways.


Subject(s)
Neural Networks, Computer , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Deep Learning , Signal Transduction/drug effects , Computational Biology/methods , Cisplatin/therapeutic use , Cisplatin/pharmacology
17.
Mol Biomed ; 5(1): 12, 2024 04 08.
Article in English | MEDLINE | ID: mdl-38584203

ABSTRACT

The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.


Subject(s)
Chromatin Assembly and Disassembly , Chromatin , Humans , Chromatin/metabolism , Chromatin/genetics , Gene Expression Regulation , Histones/metabolism , Epigenesis, Genetic , Transcription Factors/metabolism , Transcription Factors/genetics , Animals
18.
Food Chem ; 451: 139429, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38670016

ABSTRACT

Geographical traceability plays a crucial role in ensuring quality assurance, brand establishment, and the sustainable development of the crab industry. In this study, we examined the possibility of using gas chromatography-ion mobility spectrometry with multivariate statistical authenticity analysis to identify the origin of crabs from five sites downstream of the Yangtze River. Significant variations were observed in the levels of alcoholic flavor compounds in the hepatopancreas and muscles of crabs from different geographical locations, and a support vector machine exhibited discriminant ability with 100% accuracy. These flavor variations exhibited significant correlations with the types and concentrations of elements within the crabs, as well as with free amino acids. This study offers a practical approach for determining the geographical traceability of Chinese mitten crabs and elucidates the role of elements in flavor modulation, thereby providing innovative strategies to enhance the efficiency of crab farming.


Subject(s)
Brachyura , Shellfish , Animals , Brachyura/chemistry , Brachyura/classification , China , Shellfish/analysis , Flavoring Agents/chemistry , Flavoring Agents/analysis , Gas Chromatography-Mass Spectrometry , Quality Control , Taste , Geography , Hepatopancreas/chemistry
19.
Insects ; 15(3)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38535374

ABSTRACT

The genus Stictochironomus (Diptera: Chironomidae) has an almost worldwide distribution, with more than 30 species. However, species delimitation and identification based on the markings on the wings and legs are controversial and uncertain. In this study, we focused on color patterns to review the adults of the genus from China, and two new species (S. trifuscipes sp. nov. and S. quadrimaculatus sp. nov.) are described and figured. DNA barcodes can accurately separate the two new species with specific color patterns. However, heterospecific individuals form a monophyletic cluster in the phylogeny tree. For example, S. maculipennis (Meigen) and S. pictulus (Meigen), which have a lower interspecific genetic divergence, form a single clade. Sequences with the same species name but with high intraspecific distance form more than one phylogenetic clade, such as S. sticticus (Fabricius) of three clades, S. pictulus of four clades, S. akizukii (Tokunaga) and S. juncaii Qi, Shi, and Wang of two clades, might have potential cryptic species diversity. Species delimitation analysis using ASAP, PTP, and GMYC clearly delineated them as separate species. Consequently, color patterns are a good diagnostic characteristic for species delimitation in Stictochironomus. The distance-based analysis shows that a threshold of 4.5-7.7% is appropriate for species delimitation in Stictochironomus. Additionally, an updated key including color pattern variation for male adults of known Stictochironomus species from China is provided.

20.
Biochem Biophys Res Commun ; 706: 149757, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38490050

ABSTRACT

Cardiovascular disease is a main cause of mortality in the world and the highest incidence of all diseases. However, the mechanism of the pathogenesis of cardiovascular disease is still unclear, and we need to continue to explore its mechanism of action. The occurrence and development of cardiovascular disease is significantly associated with genetic abnormalities, and gene expression is affected by transcriptional regulation. In this complex process, the protein-protein interaction promotes the RNA polymerase II to the initiation site. And in this process of transcriptional regulation, transcriptional cofactors are responsible for passing cues from enhancers to promoters and promoting the binding of RNA polymerases to promoters, so transcription cofactors playing a key role in gene expression regulation. There is growing evidence that transcriptional cofactors play a critical role in cardiovascular disease. Transcriptional cofactors can promote or inhibit transcription by affecting the function of transcription factors. It can affect the initiation and elongation process of transcription by forming complexes with transcription factors, which are important for the stabilization of DNA rings. It can also act as a protein that interacts with other proteins to affect the expression of other genes. Therefore, the aim of this overview is to summarize the effect of some transcriptional cofactors such as BRD4, EP300, MED1, EZH2, YAP, SIRT6 in cardiovascular disease and to provide a promising therapeutic strategy for the treatment of cardiovascular disease.


Subject(s)
Cardiovascular Diseases , Sirtuins , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, Genetic , Nuclear Proteins/metabolism , Cardiovascular Diseases/genetics , Gene Expression Regulation , RNA Polymerase II/metabolism , Bromodomain Containing Proteins , Cell Cycle Proteins/metabolism , Sirtuins/metabolism
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