Search Results (114)

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the mechanisms underlying this competition, we developed a chimeric tethering system where the DNA-binding domains of BACH1 or NRF2 were covalently linked to sMafG via a flexible, cleavable linker. This design enables efficient heterodimer formation on DNA and circumvents kinetic barriers to partner exchange in the solution. The site-specific fluorescent labelling of proteins allowed for the tracking of complex compositions by electrophoretic mobility shift assays. Both BACH1/sMafG and NRF2/sMafG heterodimers bind CsMBEs with similar affinities. Notably, DNA binding by BACH1 was impaired in a C574-dependent, redox-sensitive manner and promoted the exchange of heterodimer partners. Competition assays demonstrated that BACH1 and NRF2 can displace each other from preformed DNA-bound complexes, with greater efficiency when presented as preassembled heterodimers with sMafG. These findings reveal a redox-sensitive mechanism for regulating transcriptional switches at CsMBEs and highlight how preformed heterodimers facilitate the rapid displacement at target promoters. Full article

Porcine circovirus 2 (PCV2) is one of the most widespread immunosuppressive viruses, impairing the protective efficacy of vaccines in pig herds. Previous studies have shown that PCV2 infection reduces the generation of immune memory and antibody secretion induced by vaccination in hosts. In this study, we used single-cell mRNA sequencing of mice splenic cells to show that PCV2 infection decelerates the differentiation of light zone germinal center (GC) B cells into memory B cells and plasma cells. We found that, although PCV2 infection led to lymphocyte depletion in the spleens of mice, the remaining splenic B cells were activated by the infection. The percentage of naïve B cells in PCV2-infected mice decreased mainly due to differentiation rather than death. Meanwhile, the percentages of memory B cells and plasma cells increased without significant enhancement of functional gene expression. Focusing on the GC B cells, we found that PCV2 infection activated the proliferation of dark zone GC B cells, but not the differentiation of light zone GC B cells. Furthermore, the transcriptional level of Prdm1 was not significantly altered by PCV2 infection, and the level of Bach2 was dramatically reduced. Further analysis showed that the interactions between light zone GC B cells and dendritic cells, macrophages, and follicular helper T cells were weakened in the spleens of PCV2-infected mice. In conclusion, this study found that PCV2 infection impairs the differentiation of B cells into functional memory B cells and plasma cells. This may be an important and previously unrecognized reason why PCV2 infection impairs vaccine efficiency. Full article

Topophilia, understood as a form of relationship between humans and their environment, can manifest in diverse ways—not only across various domains of art and life but also within the realm of music. This article seeks to expand the thesis of topophilia as a category defining the musical space of creation, performance, and perception of a musical work. Topophilia is seen here in the context of human activity in the artistic dimensions—philosophical, creative, architectural, and environmental. The methodological background is derived from the philosophy of place, phenomenology of perception, and musical analysis. This provides the opportunity to apply hermeneutic–philosophical analysis with elements of the theory of place. The thesis of this study is probably one of the first approaches to the category of topophilia in musical analysis, examining the style of composers, such as J.S. Bach, F. Chopin, K. Szymanowski, W. Lutosławski, A. Webern, and I. Xenakis, enriched with elements of musical performance. Full article

A new conformally invariant gravitational generalization of the Born–Infeld (BI) model is proposed and analyzed from the point of view of symmetries. Taking a geometric identity involving the determinant functions det$f\left(B_{\mu \nu },F_{\mu \nu }\right)$ with the Bach $B_{\mu \nu }$ and the electromagnetic field $F_{\mu \nu }$ tensors (with the 4-dimensional Greek letter indexes), two characteristic geometrical Lagrangian densities (Lagrangians) are derived: the first Lagrangian being the square root of the determinant function $\sqrt{\left|det\left(B_{\mu \nu }+F_{\mu \nu }\right)\right|}$ (reminiscent of the standard BI model) and the second Lagrangian being the fourth root $\sqrt[4]{gdet\left(B_{\alpha \gamma }{B}_{\beta }^{\gamma }+F_{\alpha \gamma }{F}_{\beta }^{\gamma }\right)}$. It is shown, after explicit computation of the gravitational equations, that the square-root model is incompatible with the inclusion of the electromagnetic tensor, consequently forcing the nullity of $F_{\mu \nu }$. In sharp contrast, the traceless fourth-root model is fully compatible and a natural ansatz of the type $B_{\mu \rho }{B}_{\nu }^{\rho }\propto \mathrm{\Omega }\left(x\right)g_{\mu \nu }$ (conformal-Killing), with $\mathrm{\Omega }$ the conformal factor and x the 4-coordinate, can be considered. Among other essential properties, the geometrical conformal Lagrangian of the fourth-root type is self-similar with respect to the determinant g of the metric tensor $g_{\mu \nu }$ and can be extended to non-Abelian fields in a way similar to the model developed by the author earlier. This self-similarity is related to the conformal properties of the model, such as the Bach currents or flows presumably of a topological origin. Possible applications and comparisons with other models are briefly discussed. Full article

BACH1 has been identified as a functional regulator of cancer metastasis and metabolic signaling in breast cancer cells. However, the clinical relevance of BACH1 expression in breast tumors remains poorly understood. Using a tissue microarray from a cohort of 130 patients, we assessed the expression of BACH1 and its known target gene, MCT1 (encoded by SLC16A1), through immunohistochemistry (IHC). The expression data were then analyzed in relation to clinical variables, including breast cancer subtypes, tissue types, tumor size and grade, patient racial background, and age group. We found positive associations between BACH1 expression and tumor size, tumor grade, and the basal-like subtype. Importantly, BACH1 expression was significantly higher in tumors from Black women compared to those from White women, as well as in the basal-like subtype of breast tumors from Black women. Additionally, a positive correlation was observed between BACH1 and MCT1 IHC scores in tumors from Black women, while a weak association was noted in tumors from White women. Our study provides compelling evidence that BACH1 expression is evident based on the race and subtypes of breast cancer patients. Full article

The intricate and complex tumor cell morphology in breast pathology images is a key factor for tumor classification. This paper proposes a lightweight breast tumor classification model with multi-frequency feature fusion (LMFM) to tackle the problem of inadequate feature extraction and poor classification performance. The LMFM utilizes wavelet transform (WT) for multi-frequency feature fusion, integrating high-frequency (HF) tumor details with high-level semantic features to enhance feature representation. The network’s ability to extract irregular tumor characteristics is further reinforced by dynamic adaptive deformable convolution (DADC). The introduction of the token-based Region Focus Module (TRFM) reduces interference from irrelevant background information. At the same time, the incorporation of a linear attention (LA) mechanism lowers the model’s computational complexity and further enhances its global feature extraction capability. The experimental results demonstrate that the proposed model achieves classification accuracies of 98.23% and 97.81% on the BreaKHis and BACH datasets, with only 9.66 M parameters. Full article

Pathological images are crucial for tumor diagnosis; however, due to their extremely high resolution, pathologists often spend considerable time and effort analyzing them. Moreover, diagnostic outcomes can be significantly influenced by subjective judgment. With the rapid advancement of artificial intelligence technologies, deep learning models offer new possibilities for pathological image diagnostics, enabling pathologists to diagnose more quickly, accurately, and reliably, thereby improving work efficiency. This paper proposes a novel Global Channel Spatial Attention (GCSA) module aimed at enhancing the representational capability of input feature maps. The module combines channel attention, channel shuffling, and spatial attention to capture global dependencies within feature maps. By integrating the GCSA module into the SegFormer architecture, the network, named GCSA-SegFormer, can more accurately capture global information and detailed features in complex scenarios. The proposed network was evaluated on a liver dataset and the publicly available ICIAR 2018 BACH dataset. On the liver dataset, the GCSA-SegFormer achieved a 1.12% increase in MIoU and a 1.15% increase in MPA compared to baseline models. On the BACH dataset, it improved MIoU by 1.26% and MPA by 0.39% compared to baseline models. Additionally, the performance metrics of this network were compared with seven different types of semantic segmentation, showing good results in all comparisons. Full article

The Duobaoshan mineralization area in Heilongjiang Province is a key copper–molybdenum–gold polymetallic region in China. Its southeastern Fudiyingzi–Bacheli area, located at the intersection of the NW-trending copper and NE-trending gold belts, exhibits favorable mineralization conditions. Despite over 70 years of placer gold mining and the discovery of one small copper deposit and one gold deposit, the area remains underexplored with significant peripheral exploration potential. This study integrates 1:50,000 geological mapping, high-precision magnetic surveys, phase-induced polarization, and soil geochemistry through multi-source data fusion for comprehensive mineral prediction. Key steps include delineating Cu, Au, and Mo anomalies and analyzing their associations with Zn, Cd, Ag, As, etc.; inferring NE-, NW-, and near-EW-trending linear structures via magnetic boundary enhancement; dividing high/low resistivity zones and identifying nine significant and six weak phase anomalies using phase-induced polarization; establishing a mineralization model based on typical deposits; and delineating four priority exploration targets. These results provide a scientific basis for further exploration in shallow coverage areas. Full article

Antioxidants neutralize reactive oxygen species and free radicals, protecting cells from oxidative damage and maintaining cellular homeostasis. In cancer therapy, they play a complex dual role, serving as protective agents against oxidative stress while, under certain conditions, acting as pro-oxidants that may promote tumorigenesis and resistance to treatment. Redox regulation is governed by key antioxidant pathways, such as the BACH1 and NRF2 pathways, along with transcriptional factors that significantly affect cancer progression and immunotherapy response. In addition to their intracellular effects, antioxidants modulate the tumor microenvironment, including interactions with the extracellular matrix, which impact cancer cell behavior and therapeutic responses. This review also explores preclinical studies that investigate the roles of major antioxidants in cancer biology. While these studies present promising data, significant challenges persist, including the potential for antioxidants to interfere with standard cancer treatments or to inadvertently support tumor survival. We further highlight emerging strategies aimed at optimizing antioxidant therapy, including personalized medicine approaches, nanoparticle-based delivery systems, and combination treatments with immunotherapies and targeted therapies. By examining the therapeutic potential and associated risks of antioxidants, this review provides critical insights into their role in cancer treatment and offers a roadmap for advancing antioxidant-based strategies to improve clinical outcomes. Full article

Objective: This study aimed to assess the prevalence of depression and anxiety among patients with acute leukemia in Vietnam and to identify associated sociodemographic and clinical factors. Methods: A cross-sectional study was conducted at the Hematology and Blood Transfusion Center of Bach Mai Hospital, a national tertiary care facility in Hanoi, Vietnam. A total of 82 patients diagnosed with acute leukemia were recruited using a convenience sampling method. Data on sociodemographic characteristics (e.g., age, gender, residence, education, occupation, marital status, and income) and clinical information (e.g., leukemia type, treatment stage, comorbidities, substance use) were collected. Depression and anxiety were assessed using the Beck Depression Inventory (BDI) and Zung’s Self-Rating Anxiety Scale (SAS). Multivariate logistic and Tobit regression analyses were applied to explore associated factors. Results: Participants had a mean age of 43.4 years (SD = 14.0), with 53.7% male and 69.5% residing in rural areas. Most were married (82.9%) and had completed high school (45.1%). Farmers constituted the largest occupational group (29.3%). The mean BDI score was 13.7 (SD = 9.8), and the mean SAS score was 39.2 (SD = 6.3). Overall, 50.0% of patients met criteria for depression, while 26.8% exhibited clinically significant anxiety symptoms. Among those with anxiety, 59.1% had mild symptoms, 22.7% moderate, and 18.2% severe or very severe. Patients with education above high school (OR = 7.32; 95% CI: 1.01–53.23), a spouse (OR = 25.10; 95% CI: 2.14–294.55), or comorbidities (OR = 8.05; 95% CI: 1.63–39.68) had significantly higher odds of depression. A higher income (>10 million VND/month) was associated with lower depression scores (Coef. = −6.05; 95% CI: −11.65 to −0.46). Regarding anxiety, the female gender was associated with higher odds (OR = 3.80; 95% CI: 1.21–11.93) and SAS scores (Coef. = 4.07; 95% CI: 1.64–6.51), while higher income predicted lower anxiety severity (Coef. = −3.74; 95% CI: −6.57 to −0.91). Conclusions: This Vietnamese hospital-based study highlights a high prevalence of depression and anxiety among patients with acute leukemia. Routine mental health screening and culturally appropriate psychosocial interventions are strongly recommended to improve patient well being. Full article

Fragile X-related disorders (FXDs) are caused by the expansion of a CGG repeat tract in the 5’-UTR of the FMR1 gene. The expansion mechanism is likely shared with the 45+ other human diseases resulting from repeat expansion, a process that has been shown to require key mismatch repair (MMR) factors. FANCJ, a DNA helicase involved in unwinding unusual DNA secondary structures, has been implicated in a number of DNA repair processes including MMR. To test the role of FANCJ in repeat expansion, we crossed FancJ-null mice to an FXD mouse model. We found that loss of FANCJ resulted in a trend towards more extensive expansion that was significant for the small intestine and male germline. This finding has interesting implications for the expansion mechanism and raises the possibility that other DNA helicases may be important modifiers of expansion risk in certain cell types. Full article

Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide, necessitating advancements in diagnostic methodologies to improve early detection and treatment outcomes. This study proposes a novel twin-stream approach for histopathological image classification, utilizing both histopathologically inherited and vision-based features to enhance diagnostic precision. The first stream utilizes Virchow2, a deep learning model designed to extract high-level histopathological features, while the second stream employs Nomic, a vision-based transformer model, to capture spatial and contextual information. The fusion of these streams ensures a comprehensive feature representation, enabling the model to achieve state-of-the-art performance on the BACH dataset. Experimental results demonstrate the superiority of the twin-stream approach, with a mean accuracy of 98.60% and specificity of 99.07%, significantly outperforming single-stream methods and related studies. Statistical analyses, including paired t-tests, ANOVA, and correlation studies, confirm the robustness and reliability of the model. The proposed approach not only improves diagnostic accuracy but also offers a scalable and efficient solution for clinical applications, addressing the challenges of resource constraints and increasing diagnostic demands. Full article

This article explores the variable properties of auditory image analysis during the perception of musical works, which are influenced by the specific elements to which the listener directs their attention. Traditional analyses of musical compositions typically involve brief comparisons with auditory phenomena described in scientific studies, such as those by A.S. Bregman. However, these analyses are often limited, offering only a narrow perspective on the works. In contrast, the approach presented in this article extends the theories and experiments developed by Bregman and others, providing a more comprehensive understanding of entire compositions or selected sections rather than focusing solely on isolated passages. This broader framework enhances auditory image analysis and serves as a foundation for further research. The expanded analysis integrates within music theory, enabling a deeper exploration of musical structures, particularly in the context of perceiving multilayered music where multiple sound sources may share similar acoustic features. The author illustrates how acoustic and perceptual factors contribute to complex mental representations through graphic and musical examples. To substantiate the claims, classical works by composers such as F. Chopin, A. Guilmant, and J.S. Bach are analysed, further highlighting the variable properties of auditory image analysis. Full article

Background: The microbiological profile of bone and joint infections is important for determining the empiric choice of both systemic and local antimicrobial therapy. This study assessed whether there was a difference in the bacterial species that were isolated on culture in osteomyelitis (OM), fracture-related infection (FRI) or prosthetic joint infection (PJI). This was a retrospective, observational cohort study of patients who had surgical intervention for PJI or OM or FRI with a positive microbial culture between 2019 and 2022. Methods: Data including patient demographics, the site of injury, JS-BACH score, organism classification and antibiotic resistance to vancomycin and gentamicin were extracted from the medical records. Results: A total of 440 patients were included in this study: 163 patients with osteomyelitis, 109 with fracture-related infection with fixation implants and 168 with prosthetic joint infection. The patients with PJI were older, more likely to be female and had a higher BMI and ASA score compared to those with OM. Patients with PJI were more likely to have a higher JS-BACH score and more complex infections. Staphylococcus aureus was the most commonly isolated organism in all three groups. It was more frequently isolated in osteomyelitis than in PJI (p = 0.016). In both osteomyelitis and FRI, after Staphylococcus aureus, the next most common organisms were Gram-negatives, whilst for PJIs, the most commonly isolated organisms were Staphylococcus aureus, followed by coagulase-negative Staphylococci and then Streptococcus species. The rates of other organisms were broadly similar between the three groups. When adjusted for confounders, including symptom duration, JS-BACH score, the location of injury, age and BMI, there was no statistically significant difference in the presence of Staphylococcus aureus (OR = 0.765; 95% CI 0.633–1.232; p = 0.465) or polymicrobial infection (OR = 1.175; 95% CI 0.803–1.721; p = 0.407). Conclusions: Causative pathogens are similar across bone and joint infections and are independent of the presence of prosthetic material. Full article

Elevated fetal hemoglobin (HbF), which is partly controlled by genetic modifiers, ameliorates disease severity in β hemoglobinopathies. Understanding the genetic basis of this trait holds great promise for personalized therapeutic approaches. PubMed, MedRxiv, and the GWAS Catalog were searched up to May 2024 to identify eligible GWAS studies following PRISMA guidelines. Four independent reviewers screened, extracted, and synthesized data using narrative and descriptive methods. Study quality was assessed using a modified version of the Q-Genie tool. Pathway enrichment analysis was conducted on gene lists derived from the selected GWAS studies. Out of 113 initially screened studies, 62 underwent full-text review, and 16 met the inclusion criteria for quality assessment and data synthesis. A total of 939 significant SNP-trait associations (p-value < 1 × 10⁻⁵) were identified, mapping to 133 genes (23 with overlapping variant positions) and 103 intergenic sequences. Most SNP-trait associations converged around BCL11A (chr.2), HBS1L-MYB, (chr.6), olfactory receptor and beta globin (HBB) gene clusters (chr.11), with less frequent loci including FHIT (chr.3), ALDH8A1, BACH2, RPS6KA2, SGK1 (chr.6), JAZF1 (chr.7), MMP26 (chr.11), COCH (chr.14), ABCC1 (chr.16), CTC1, PFAS (chr.17), GCDH, KLF1, NFIX, and ZBTB7A (chr.19). Pathway analysis highlighted Gene Ontology (GO) terms and pathways related to olfaction, hemoglobin and haptoglobin binding, and oxygen carrier activity. This systematic review confirms established genetic modifiers of HbF level, while highlighting less frequently associated loci as promising areas for further research. Expanding research across ethnic populations is essential for advancing personalized therapies and enhancing outcomes for individuals with sickle cell disease or β-thalassemia. Full article