Browse Articles

NBS1 facilitates preribosomal RNA biogenesis

Mutations in the NBS1 gene result in Nijmegen breakage syndrome (NBS), and the gene encodes NBS1 that forms a complex with MRE11 and RAD50 and participates in DNA damage repair. However, the molecular mechanism by which NBS1 mutations cause clinical phenotypes of NBS, such as craniofacial dysmorphism, is still unclear. Here, we show that NBS1 localizes at the ribosomal DNA (rDNA) loci in nucleoli and interacts with ribosomal RNA (rRNA) transcription machinery including RNA polymerase I (Pol I) and TCOF1. Loss of NBS1 impairs Pol I-dependent transcription of pre-rRNA and induces nucleolar stress. In particular, lacking Nbs1 in mouse neural crest cells not only leads to the reduction of ribosome biogenesis but also craniofacial abnormalities during prenatal development. Moreover, the C-terminus of NBS1 is associated with pre-rRNA and a number of pre-rRNA processing factors, which may also facilitate pre-rRNA maturation. Taken together, our study reveals the functions of NBS1 in rRNA biogenesis.

Mediodorsal thalamus regulates task uncertainty to enable cognitive flexibility

Enhancement of standardized precipitation evapotranspiration index predictions by machine learning based on regression and soft computing for Iran’s arid and hyper–arid region

Drought is a climate risk that affects access to safe water, crop development, ecological stability, and food production. Therefore, developing drought prediction methods can lead to better management of surface and groundwater resources. Similarly, machine learning can be used to find improved relationships between nonlinear variables in complex systems. Initially, the standardized precipitation evapotranspiration index (SPEI) was calculated, and then using large–scale signals such as large–scale climate signals (the North Atlantic Oscillation, the Arctic Oscillation, the Pacific Decadal Oscillation, and the Southern Oscillation Index), along with climatic variables including temperature, precipitation, and potential evapotranspiration, predictions were made for the period of 1966–2014. Several new machine learning models including Least Square Support Vector Regression (LSSVR), Group Method of Data Handling (GMDH), and Multivariate Adaptive Regression Splines (MARS) were used for prediction. The results showed that in estimating SPEI in moderately arid climates, the GMDH model with criteria (RMSE = 0.26, MAE = 0.17, NSE = 0.95 in validation) under scenario S1 (included all variables plus the SPEI of the previous month) performed better, while in arid and cold climates, the LSSVR model (RMSE = 0.22, MAE = 0.18, NSE = 0.95 in validation) under S1, and in arid and hot climate, the LSSVR model (RMSE = 0.29, MAE = 0.19, NSE = 0.93 in validation) under scenario S2 (included meteorological variables plus the SPEI of the previous month) had higher prediction accuracy. Although the MARS model was less accurate in validation, it showed higher accuracy during calibration compared to the other two models in all climates. The results showed that using large–scale signals for predicting SPEI was beneficial. It can be concluded that machine learning models are useful tools for predicting the SPEI drought index in different climates within similar ranges.

Author Correction: Endurance exercise attenuates Gαq-RNAi induced hereditary obesity and skeletal muscle dysfunction via improving skeletal muscle Srl/MRCC-I pathway in Drosophila

Cryo-ET reveals the in situ architecture of the polar tube invasion apparatus from microsporidian parasites

Microsporidia are divergent fungal pathogens that employ a unique harpoon-like apparatus called the polar tube (PT) to invade host cells. The long PT is fired out of the microsporidian spore over the course of just a few hundred milliseconds. Once fired, the PT is thought to pierce the plasma membrane of a target cell and act as a conduit for the transfer of the parasite into the host cell, which initiates infection. The PT architecture and its association with neighboring organelles within the parasite cell remain poorly understood. Here, we use cryoelectron tomography to investigate the structural cell biology of the PT in dormant spores from the human-infecting microsporidian species, Encephalitozoon intestinalis . Segmentation and subtomogram averaging of the PT reveal at least four layers: two protein-based layers surrounded by a membrane layer and filled with a dense core. Regularly spaced protein filaments form the structural skeleton of the PT. Combining cryoelectron tomography with cellular modeling, we propose a model for the three-dimensional organization of the polaroplast, an organelle that surrounds the PT and is continuous with the outermost, membranous layer of the PT. Our results reveal the ultrastructure of the microsporidian invasion apparatus in situ, laying the foundation for understanding infection mechanisms.

Author Correction: Real-world time-travel experiment shows ecosystem collapse due to anthropogenic climate change

Effects of occupational therapy synchronized with dual transcranial direct current stimulation on upper limb function and electroencephalography power in subacute stroke patients: A randomized, double-blind, controlled study

Background Occupational therapy (OT) and transcranial direct current stimulation (tDCS) are both important methods for promoting the recovery after stroke. There are limited researches that simultaneously apply both methods and investigate their effects on upper limb function. Objective To investigate the effects of OT synchronized with dual tDCS on upper limb motor function and Electroencephalogram (EEG) power in subacute stroke patients. Methods Forty-five subacute stroke patients were randomly assigned to control group (n = 23) and experimental group (n = 22), receiving sham and real dual tDCS concurrent with OT respectively, five times a week, for a duration of two weeks. Upper limb motor function and cortical EEG power were evaluated by Fugl-Meyer Assessment Upper Extremity (FMA-UE), Modified Barthel Index (MBI) and Action Research Arm Test (ARAT), Delta/Alpha Ratio (DAR) and pairwise derived Brain Symmetry Index (pdBSI) at baseline and two weeks. Results Finally, a total of 39 patients completed the study and were included in the analysis. The results revealed that participants in the experimental group showed a significant better evolution for FMA-UE (p < 0.001), MBI (p = 0.034), DAR in the primary motor cortex (M1) area (p = 0.022) and pdBSI (p = 0.025) compared to the control group. Conclusions In subacute stroke patients, the central-peripheral combined stimulation approach, which involves dual tDCS (central stimulation) and synchronous OT (peripheral sensory-motor stimulation) enhanced the effects of OT alone, leading to greater improvements in upper limb function and normalization of brain activity. Trial registration This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2400082749).

Salivary apoptotic microvesicles as biomarkers for prognostic non-healing oral ulcers and oral cancer: a cross-sectional study

Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity

To ensure optimal replication and spread, viruses have evolved countermeasures to evade type 1 IFN-mediated antiviral activity. During the early viral replication cycle steps until uncoating, the HIV-1 core protects viral pathogen associated molecular patterns (viral RNA and reverse transcription products) from recognition by innate immune sensors, including cGAS. However, after capsid uncoating, unintegrated viral DNA (uvDNA) becomes accessible. Here, we show that HIV-1 uses chromatin-mediated cGAS inactivation as a mechanism to protect its uvDNA from innate immune activation.

Wearable flexible ultrasound microneedle patch for cancer immunotherapy

Axial compressive behavior of lithium slag and rubber concrete-filled steel tube stub columns

In order to solve the harm of industrial waste such as lithium slag and waste rubber to the environment, this paper put forward the structure of lithium slag and rubber concrete-filled steel tube (LSRuCFST) stub column, which was replaced cement and sand in concrete by lithium slag and waste rubber respectively. Through the axial compression test of 11 LSRuCFST specimens with various lithium slag replacement ratios (0, 10%, 20%, 30%) and rubber replacement ratios (0, 5%, 10%, 20%, 30%), the damage patterns and mechanical characteristics of LSRuCFST columns were studied. The experimental phenomena showed that the damage patterns of 11 specimens were similar to the ordinary concrete-filled steel tube (CFST) colunms. With 20% replacement ratio of lithium slag and 10% replacement ratio of rubber, the largest increase of bearing capacity was optimal. Then, the bearing capacities of LSRuCFST columns were investigated by domestic and international standards. Due to conservative predicted results, a modified computational formal for the LSRuCFST column bearing capacity was presented and verified by the test results of references.

Rapid inactivation of bacteria by MoS2/g-C3N4 nanohybrid structures driven by visible light

GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL

Inflammation is among the known causes of cisplatin-induced hearing loss (CIHL), but its exact pathophysiological mechanisms remain unclear. Herein, we demonstrated that pyroptosis—a recently identified inflammatory type of regulated cell death dependent on gasdermin D (GSDMD)—was activated in the cochleae of cisplatin-treated mice, causing CIHL. Meanwhile, treatment with the GSDMD inhibitor necrosulfonamide alleviated CIHL in these mice. To further examine the role of GSDMD-mediated pyroptosis in CIHL, we conducted experiments in Gsdmd- deficient mice . Gsdmd −/− mice demonstrated significantly lower cisplatin-induced cochlear damage than control mice and appeared to be invulnerable to CIHL. Furthermore, GSDMD-mediated pyroptosis in the stria vascularis (SV), but not in the hair cells (HCs), played a dominant role in CIHL. In marginal cells (MCs) of SV, cisplatin induced caspase-dependent GSDMD cleavage, and the pore-forming N-terminal of GSDMD rapidly localized to the mitochondria, leading to abnormal mitochondrial aggregation and oxidative stress. The consequent mitochondrial dysfunction in MCs might result in the severe progression of inflammation, SV damage, and HC loss. Notably, the pharmacological inhibition of pyroptosis using the FDA-approved drug disulfiram effectively alleviated the symptoms of CIHL. Collectively, these findings offer a broad avenue for inhibiting pyroptosis-induced cisplatin ototoxicity and provide valuable theoretical insights for the clinical management of CIHL.

Retraction: Control of hybrid electromagnetic bearing and elastic foil gas bearing under deep learning

A systematic review and meta-analysis of the prevalence and risk of syphilis among blood donors in Thailand

Abstract Despite rising rates of sexually transmitted infections (STIs) in Thailand, including syphilis, data on its prevalence and associated risk factors among blood donors remain scarce. This systematic review and meta-analysis aimed to estimate the prevalence of syphilis and identify the key risk factors among blood donors in Thailand to inform targeted interventions for enhanced blood safety.The study protocol was registered in PROSPERO (CRD42024560215) and conducted following PRISMA guidelines. Comprehensive searches were performed across major databases, including ProQuest, Journals@Ovid, Embase, Scopus, PubMed, and MEDLINE, to identify relevant studies. A random-effects model was used to calculate the pooled prevalence and odds ratios (ORs) for syphilis risk factors. Heterogeneity was quantified using the I² statistic, and meta-regression and subgroup analyses were employed to explore potential sources of heterogeneity. Publication bias was assessed using funnel plots and Egger’s regression test. A total of 23 studies involving 1,142,910 blood donors were included. The pooled prevalence of syphilis among blood donors in Thailand was 0.42% (95% CI 0.27–0.66%, I²: 99.3%, number of infections: 6,173), with a decreasing trend over time. Male donors were significantly more likely to have syphilis (P < 0.0001; pooled OR: 1.76; 95% CI 1.53–2.03; I²: 34.2%, 651,019 participants). First-time donors also had an elevated risk of syphilis (P = 0.02; pooled OR: 2.02; 95% CI 1.10–3.70; I²: 94.0%, 215,245 participants). Additionally, the analysis revealed a significant association between increasing age and higher syphilis risk among blood donors. The systematic review and meta-analysis indicated that syphilis prevalence among blood donors in Thailand is declining; however, male and first-time donors, as well as older age groups, remain at higher risk. To enhance blood safety, targeted interventions are needed, including refining donor screening questionnaires, expanding educational campaigns for high-risk groups, and incorporating advanced screening technologies. Strengthening and regularly updating national screening policies will ensure the effective mitigation of syphilis transmission among blood donors in Thailand.

Expansion and pathogenic activation of skeletal muscle–resident macrophages in <i> mdx ^5cv /Ccr2 ^−/− </i> mice

Infiltrating macrophages contribute to muscle dystrophic changes in Duchenne muscular dystrophy (DMD). In a DMD mouse model, mdx 5cv mice, CC chemokine receptor type 2 (CCR2) deficiency diminishes Ly6C hi macrophage infiltration by blocking blood Ly6C hi inflammatory monocyte recruitment. This is accompanied by transient improvement of muscle damage, fibrosis, and regeneration. The benefit, however, is lost after the expansion of intramuscular Ly6C lo macrophages. To address the mechanisms underlying the Ly6C lo macrophage expansion, we compared mdx 5cv /Nur77 −/− and mdx 5cv /Ccr2 −/− /Nur7 −/− mice with mdx 5cv and mdx 5cv /Ccr2 −/− mice, respectively, and found no evidence to suggest Ly6C lo monocyte recruitment by dystrophic muscles. Single-cell RNA sequencing analysis and Flt3 cre /Rosa26 LSL-YFP -based lineage tracing of macrophage origins demonstrated the expansion and pathogenic activation of muscle resident macrophages in CCR2-deficient mdx 5cv mice. The expansion was associated with increased cell proliferation, which appeared induced by colony-stimulating factor-1 (CSF-1) derived from fibro/adipogenic progenitors (FAPs). Our study establishes a pathogenic role for skeletal muscle resident macrophages and supports a regulatory role of FAPs in stimulating the expansion of resident macrophages in the DMD mouse model when the inflammatory macrophage infiltration is inhibited.

Potential multiple disease progression pathways in female patients with Alzheimer’s disease inferred from transcriptome and epigenome data of the dorsolateral prefrontal cortex

Late-onset Alzheimer’s disease (AD) is a typical type of dementia for which therapeutic strategies have not yet been established. The database of the Rush Alzheimer’s Disease study by the ENCODE consortium contains transcriptome and various epigenome data. Although the Rush AD database may contain a satisfactory amount of data for women, the amount of data for men remains insufficient. Here, based on an analysis of publicly available data from female patients, this study found that AD pathology appears to be nonuniform; AD patients were divided into several groups with differential gene expression patterns, including those related to cognitive function. First, cluster analysis was performed on individuals diagnosed with “No Cognitive Impairment (NCI),” “Mild Cognitive Impairment (MCI),” and “Alzheimer’s Disease (AD)” stages in clinical trials using gene expression, and multiple substages were identified across AD progression. The epigenome data, in particular genome-wide H3k4me3 distribution data, also supported the existence of multiple AD substages. However, APOE gene polymorphisms of individuals seemed to not correlate with disease stage. An inference of adjacency networks among substages, evaluated via partition-based graph abstraction using the gene expression profiles of individuals, suggested the possibility of multiple typical disease progression pathways from NCI to different AD substages through various MCI substages. These findings could refine biomarker discovery or inform personalized therapeutic approaches.

Online high speed detection method for end face quality of cored filter rods under complex conditions

Epstein–Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging

Epstein–Barr virus (EBV) is strongly implicated in the pathogenesis of multiple sclerosis (MS), yet its exact role in disease progression remains unclear. Using high-dimensional CO-detection by indexing, a technology for spatial imaging, this study examines the cellular microenvironment of MS lesions in secondary progressive MS and primary progressive MS. We analyzed immune, glial, neuronal, and endothelial cell interactions within MS lesions and normal-appearing white matter across two independent cohorts. Our findings show the enrichment of EBV markers, particularly EBNA1 and LMP1, within MS lesions. EBV-positive cells interact closely with reactive astrocytes, microglia, and neurons. Image analysis confirmed the presence of EBV-positive staining within neurons and glial cells, suggesting a direct role for EBV in neuronal and glial involvement in MS. Additionally, we observed altered immune cell interactions, including reduced associations with macrophages and memory T cells, and enhanced interactions with glial cells. Disruptions in blood–brain barrier integrity were also noted in regions of the MS brain. These results highlight EBV’s contribution to immune modulation, glial dysfunction, and neuronal damage in MS, particularly in progressive subtypes. The analysis of MS brain tissue suggests potential therapeutic targets, including antivirals and brain penetrant immune modulators, to address EBV’s impact on MS progression.

An evidence-based guidance framework for neural network system diagrams

Accurate communication of research is essential. We present the first evidence-based framework for formatting neural network architecture diagrams within scholarly publications. Neural networks are a prevalent and important machine learning component, and their application is leading to significant scientific progress in many domains. Diagrams are key to their communication, appearing in almost all papers describing novel systems. However, there are currently no established, evidenced-based conventions describing how they should be presented. We study the use of neural network system diagrams through interviews, card sorting, and qualitative feedback structured around ecologically-derived example diagrams. We find that diagrams in scholarly publications can be difficult to interpret due to ambiguity and variance in their presentation, and that there is a high diversity of usage, perception and preference in both the creation and interpretation of diagrams. We examine the results in the context of existing design, information visualisation, and user experience guidelines and use this foundation to derive a framework for formatting diagrams, which is evaluated through an experimental study, and a comprehensive “corpus-based” approach examining properties of published diagrams in top neural network venues. The studies demonstrate that 1) both the usability and utility of the framework are high and 2) papers containing diagrams that conform to the guidelines receive more citations than those containing diagrams that violate them.