Browse Articles

A 3’UTR-derived small RNA modulates the life cycle of the cholera toxin–encoding filamentous phage, CTXϕ

Bacteriophages (phages) are well known to be one of the major driving forces in bacterial evolution. This also applies to virulent microorganisms, such as the major human pathogen Vibrio cholerae , whose pathogenic potential and epidemic proliferation largely depends on the interaction with environmental phages. Specifically, integration of the CTXϕ phage genome into the first chromosome of V. cholerae also introduced the ctxAB genes, encoding the primary toxin responsible for the severe acute diarrheal disease, cholera. Whereas the mechanisms underlying CTXϕ-associated horizontal gene transfer and transcriptional control of the ctxAB genes have been intensively studied over the past years, posttranscriptional regulation affecting the CTXϕ life cycle has not been documented. Here, we report the identification and characterization of the CisR small RNA (sRNA) that is produced from the 3’UTR (untranslated region) of the prtV gene and inhibits the expression of the CTXϕ-encoded cep mRNA. CisR-mediated repression of cep involves Hfq-assisted base-pairing of the two transcripts and results in reduced CTXϕ production under stress conditions. We further demonstrate that transcription of prtV-cisR requires both the master quorum-sensing regulator HapR and CRP (cAMP receptor protein), a global regulator of carbon metabolism. Taken together, our work provides evidence that V. cholerae employs sRNA-mediated posttranscriptional gene regulation to coordinate CTXϕ activation with both cell density and nutrient availability.

A deep learning-based fusion framework for robust fine-grained classification of sea turtles in support of marine biodiversity

Accurate classification of sea turtle species is crucial for ecological monitoring and conservation, yet traditional visual classification methods remain limited by underwater imaging challenges such as occlusions, poor lighting, and background noise. To address these limitations, we propose an enhanced deep learning-based classification framework that integrates both color and structural features to improve the robustness of species recognition in complex marine environments. Building upon the ResNet-50 backbone, we introduce a four-channel input tensor comprising RGB data and Sobel-filtered edge maps, capturing both semantic and morphological information. Two novel fusion modules, LiteAFNet and AlphaBlendNet, are designed to integrate these features effectively. LiteAFNet leverages a lightweight attention mechanism to highlight discriminative regions, while AlphaBlendNet adaptively balances RGB and edge cues based on spatial context. Experimental results demonstrate significant improvements in classification performance across all evaluation metrics. Specifically, AlphaBlendNet achieves the highest precision (0.84), recall (0.88), F1-score (0.86), and mean average precision (mAP) of 87.2%, outperforming both the baseline fusion and LiteAFNet configurations. These results indicate that integrating color histograms with structural edge features enhances the model’s ability to distinguish between species with similar visual traits. This framework offers a scalable, accurate, and automated solution for underwater species classification and holds potential for broader application in marine biodiversity monitoring.

Health literacy, adherence to prevention practices, and attitudes towards caring for infectious patients among medical and nursing students - a cross-sectional study

Abstract Healthcare students’ attitudes towards taking care of infectious patients and adherence to prevention measures are necessary for future epidemics, and might be defined by their level of health literacy. Therefore, we aim to describe health literacy, adherence to prevention practices, and attitudes towards taking care of infectious patients of students at Hanoi Medical University and their associated factors during the COVID-19 pandemic in 2020. A cross-sectional study was conducted at Hanoi Medical University in April 2020, using total population sampling ( N  = 3,672). Data was collected using an online questionnaire consisting of demographic, academic, health-related factors, fear of COVID-19, health literacy, adherence to prevention practices, and a direct question about attitude towards taking care of infectious patients. Poisson regression was applied to assess the association between the outcome and other factors. Among 1,583 participants (43.1% response rate), the overall median Health Literacy score was 33.33 (IQR: 29.17–34.72) and was higher among participants with clinical experiences, better ability to pay for medications, and studying preventive medicine. The percentage of people having good adherence to all prevention practices was 55.1% (95% CI 52.6–57.5%). The frequency of handwashing, social distancing, and mask-wearing was 86.8% (95% CI 85.0–88.4%), 60.2% (95% CI 57.8–62.6%), and 96.5% (95% CI 95.5–97.3%), respectively. Most respondents had neutral attitudes towards caring for infectious patients (53.1%; 95% CI 50.7–55.6%). Our Poisson regression analysis showed that Health Literacy was positively associated with adherence to prevention measures. This study found no statistical correlation between Health Literacy and attitudes towards taking care of infectious patients. Health Literacy training and mental and financial support for medical undergraduates could be the key to improving health behaviors among medical students. More studies are needed to identify factors that could enhance the positive attitudes towards taking care of infectious patients in the future.

Positive allosteric modulator selective for adult muscle nicotinic acetylcholine receptor

The muscle nicotinic acetylcholine receptor (AChR) is the key mediator of neuromuscular signal transmission and is essential for all voluntary movement in our body. In this study, we present DC-98-LC74, a positive allosteric modulator (PAM) for the adult skeletal muscle-type AChR. Through using Ca 2+ fluorometric imaging plate reader (FLIPR) assays, we demonstrate that it is selective for the adult skeletal muscle AChR over neuronal subtypes. Neurophysiological recordings from ex vivo mouse diaphragm preparations revealed that DC-98-LC74 elongates the endplate currents of wildtype (WT) adult but not fetal channel containing diaphragms. Single channel studies on chimeric channels of the adult and fetal receptor, and in saturating concentrations of choline, suggest that the PAM does not bind at either orthosteric site, but works by increasing the unliganded open probability via a mechanism that involves the ε M2-M3 loop. We also show that DC-98-LC74 increases the burst duration of multiple fast channel mutant AChR to WT levels, suggesting that positive allosteric modulation could be a therapeutic strategy for this difficult to treat subtype of congenital myasthenia. Promising preliminary data on aged sarcopenic mice also demonstrate that positive allosteric modulation of the muscle type AChR has potential benefits not only in myasthenia but also other neuromuscular disorders involving the neuromuscular junction.

Metabolite profiling of saliva for the discrimination of Behcet’s disease, Sjögren’s syndrome, and recurrent aphthous stomatitis

Oral manifestations can be the initial sign of systemic diseases such as Behcet’s disease (BD) and Sjogren’s syndrome (PSS). Their frequency and morphology vary widely, and recurrent aphthous stomatitis (RAS) often mimics BD ulcers, complicating differentiation on clinical grounds. Nonspecific aphthoid lesions are also seen in PSS. This study aimed to identify distinctive metabolic patterns in saliva that could discriminate BD, PSS, and RAS using global metabolite profiling. Saliva samples were collected from 43 patients (BD, n = 24; PSS, n = 10; RAS, n = 9) after fasting and abstaining from oral activities for at least 90 minutes. Gas chromatography-mass spectrometry (GC/MS) was employed for metabolite profiling. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) were used to distinguish groups. Variable importance in projection (VIP) scores were calculated from partial least squares discriminant analysis (PLS-DA), and ANOVA was applied to compare metabolite abundance. Forty-two metabolites were identified and categorized into amino acids, organic acids, sugars, sugar alcohols, and others. PCA and HCA demonstrated clear dis-crimination among BD, PSS, and RAS. Metabolites with VIP > 1 included malonic acid sorbitol, pyroglutamic acid, aspartic acid, decanoic acid, hexadecenoic acid, and L-proline. Notably, malonic acid and aspartic acid were significantly elevated in BD compared to PSS and RAS, suggesting their diagnostic potential. Global salivary metabolite profiling by GC/MS provides distinct metabolic signatures enabling discrimination among BD, PSS, and RAS. This approach may enhance understanding of oral mucosal manifestations in systemic autoimmune diseases.

HOG-supervised compact CNNs for real-time visual place recognition

Mean field game model of the impact of reductions in support on faculty research activity

Every research university has a distribution of faculty research activity that is fueled by the external support from government, industry, and philanthropy. The large decreases in federal support proposed in 2025 by the Administration would dramatically alter the distribution of faculty research activity. Mean field game (MFG) theory is used to model federal support of faculty research assuming that each researcher seeks to maximize their funding according to a specified utility function. Modeling the collection of researchers as a continuum with individual researchers only influenced by the distribution of others—referred to as the mean field—predicts ergodic distributions that represent a Nash equilibrium. Results representing the funding for faculty in colleges of engineering demonstrate that a decrease in overall federal support of the magnitude proposed by the Administration could lead to over half the faculty inadequately funded to support research. The results have important implications to the university research environment and to their strategies for maintaining the vibrancy of their programs.

Expression of Concern: A modified fractional short circuit current MPPT and multicellular converter for improving power quality and efficiency in PV chain

Facilitation of hippocampal long-term potentiation by astrocytic Gq signaling is compromised in an advanced Alzheimer’s disease model

TadA-mediated A-to-I mRNA editing rewires redox metabolism to promote dominance of epidemic <i> <i>Klebsiella pneumoniae</i> </i> clones

Dominant carbapenem-resistant Klebsiella pneumoniae (CRKP) clones have markedly intensified the burden of invasive infections while severely restricting treatment options. Although genomic determinants of these high-risk lineages are well characterized, adaptive regulatory mechanisms beyond fixed DNA variation remain poorly understood. Here we systematically map the adenosine-to-inosine (A-to-I) mRNA editing landscape in CRKP and reveal that clinically dominant lineages possess a constrained and clone-specific landscape of RNA editing. We identify PncR (a previously uncharacterized AraC/XylS family transcription factor) and the response regulator DcuR as prominent A-to-I editing targets enriched in high-risk clones. Editing of these regulators reshapes redox and metabolic programs, thereby increasing tolerance to oxidative stress associated with innate immune attack. These results support a model in which stress-responsive RNA editing promotes stress adaptation specifically in high-risk CRKP clones. Furthermore, we demonstrate that the tRNA deaminase TadA is the sole A-to-I editing enzyme in K. pneumoniae , and that its abundance determines both the extent and diversity of mRNA editing. These findings establish TadA-driven A-to-I editing as a selectable, posttranscriptional regulatory layer that reshapes bacterial metabolism and promotes the success of high-risk CRKP lineages, highlighting this axis as a potential target for therapeutic intervention.

Study on tensile mechanical response and microstructure of polypropylene fiber reinforced loess under freezing

Tensile strength is one of the key parameters in the mechanics of frozen ground, widely applied in the engineering design of frozen ground and theoretical research on frost heave. Fiber-reinforced soil technology has attracted considerable attention from numerous researchers. This study utilised a custom-designed tensile testing apparatus to investigate the influence of polypropylene fiber content, freezing temperature, and loading rate on the mechanical response of frozen loess. Combined with microscopic structural observations, the research elucidates the fiber reinforcement mechanism. Experiments revealed that fiber incorporation transformed the soil’s failure mode from brittle fracture to ductile failure, characterised by multiple fissures, significantly enhancing the material’s load-bearing capacity and deformation properties. Optimal reinforcement was achieved at a fiber content of 0.3%, with tensile strength increasing by 71.4% compared to unfibered soil. The stress-strain response exhibited sustained strengthening characteristics. Tensile strength exhibits exponential growth with decreasing freezing temperatures and linear increase with rising loading rates. The incorporation of fibers further enhances the material’s response capability under dynamic loading conditions. Microstructural analysis indicates that an appropriate fiber content effectively fills soil pores and forms a spatial network structure, whereas excessive fibers cause agglomeration due to uneven distribution, resulting in structural weakening. This research provides experimental evidence and theoretical reference for the design and application of fiber-modified frozen ground in engineering projects within cold regions

Evaluation of the platelet-to-white-cell ratio (PWR) as predictor of long-term all-cause mortality in patients with acute myocardial infarction

Abstract The platelet-to-white-cell ratio has recently gained attention as a potential prognostic indicator. This study investigated the association between platelet-to-white-cell ratio at admission and long-term mortality in acute myocardial infarction patients, in comparison to leukocyte and platelet counts alone. The study included 4,964 patients aged 25–84 years with incident acute myocardial infarction hospitalized between 2010 and 2017, as recorded in the population-based Augsburg Myocardial Infarction Register. Platelet-to-white-cell ratio was calculated from admission platelets divided by leukocyte counts. Cox proportional hazards regression models were used to assess the associations between quartiles of platelet-to-white-cell ratio, of leukocytes, and of platelets with long-term all-cause mortality. During a median follow-up time of 4.7 years, 1,224 patients died. Platelet count in the highest quartile was observed to be associated with increased mortality risk (HR 1.32 (1.06–1.63). Platelet-to-white-cell ratio values were also found to be associated with risk of mortality. Multivariable adjusted HRs for the second, third, and fourth quartiles of platelet-to-white-cell ratio (vs. lowest quartile) were 0.64 (95% CI: 0.52–0.80), 0.83 (0.67–1.03), and 0.78 (0.62–0.98), respectively. Platelet-to-white-cell ratio at admission was associated with long-term mortality in patients with acute myocardial infarction. As a simple, cost-effective biomarker, platelet-to-white-cell ratio may support individualized risk stratification and clinical decision-making in acute myocardial infarction care.

15-PGDH inhibition promotes muscle repair and strength recovery during GLP-1 receptor agonist–induced weight loss

Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are transformative anti-obesity therapies. However, emerging evidence indicates that weight loss may come at the expense of skeletal muscle mass, a tissue essential for mobility, metabolic regulation, and overall health. Here, we show that inhibition of the gerozyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme that increases with injury and aging, improves muscle repair and strength recovery in the presence of semaglutide. In a high fat diet-induced mouse model of obesity, semaglutide alone caused significant loss of muscle mass, while preserving contractile function. Following injury, obese mice exhibited pathological calcifications previously reported for the heritable myopathy, Duchenne Muscular Dystrophy. Semaglutide had both beneficial and deleterious effects, reducing calcific remodeling, but causing reduced regenerated myofiber sizes. This impaired regenerative myofiber growth in semaglutide-treated mice was surmounted by cotreatment with a 15-PGDH inhibitor (PGDHi), which stimulated muscle stem cell function and myofiber growth, leading to enhanced strength. Importantly, PGDHi synergizes with semaglutide to boost postinjury muscle quality and muscle force without compromising weight loss.

Study on the safety evaluation of latent tuberculosis treatment in high‑risk groups for tuberculosis development: Study protocol for a multi‑center prospective observational cohort study in Korea (STEP-TB)

Background Tuberculosis preventive treatment (TPT) is essential for tuberculosis elimination; however, evidence on its safety and feasibility in medically complex, high-risk populations is limited. Concerns regarding adverse events frequently hinder treatment initiation and completion in routine clinical practice. Objectives The Safety of Preventive Treatment in People at Risk for Tuberculosis (STEP-TB) study aims to generate real-world evidence on the safety of TPT among individuals at high risk of developing active tuberculosis disease and to identify factors associated with adverse events, treatment initiation, adherence, and completion. Methods STEP-TB is a multicenter, prospective observational cohort study conducted at four university-affiliated hospitals in the Republic of Korea. Adults aged ≥19 years who are eligible for latent tuberculosis infection (LTBI) testing or TPT according to national guidelines will be enrolled, including individuals with chronic kidney disease, chronic lung disease, diabetes mellitus, immunosuppressive conditions, malignancy, or occupational risk. LTBI testing will be performed using interferon-gamma release assays, and TPT regimens will follow national guidelines. Participants initiating TPT will be followed for up to 12 months from treatment initiation. Those with negative LTBI results or without TPT will be also followed for up to 12 months. Adverse events, treatment adherence, and completion will be systematically assessed. Blood samples, including volumetric absorptive microsampling, will be collected in a subset of participants for pharmacokinetic and pharmacogenetic analyses. Outcomes The primary outcome is the occurrence of adverse events during TPT. Secondary outcomes include TPT completion rates, predictors of non-initiation and discontinuation, and progression to active TB. Conclusion STEP-TB will provide condition-specific, real-world evidence on TPT safety and implementation, informing clinical decision-making, patient-centered care, and national TB control policies to support the safe expansion of LTBI treatment strategies in Korea. CRIS Registration Number: KCT0011063

Ubiquitination of Smad2 by Smurf1 inhibits endothelial-to-mesenchymal transition in human coronary artery endothelial cells

Self-activation by a C-terminal domain arginine finger regulates GTP hydrolysis in bacterial zinc metallochaperones

The cellular response to transition metal scarcity is multifaceted and complex. Members of the Cluster of Orthologous Groups 0523 (COG0523) superfamily are proposed to chaperone a bound metal to activate an apoenzyme client and are thus candidate metallochaperones. COG0523 enzymes are GTPases that harbor a conserved Ras-like guanosine-5‘-triphosphate (GTP)-binding and hydrolysis domain (G-domain) and a C-terminal domain (CTD) of unknown function connected by a flexible linker. AlphaFold3 modeling posits an “open” GTPase-inactive and “closed” GTPase-active conformation where the GTP and switch 1 (G2) loop are buried at the interface of the two domains. We show here that the CTD functions as a GTP-hydrolysis activation protein (GAP) domain that stimulates GTP hydrolysis by the tethered G-domain. This “self-activation” requires an invariant RxK sequence in the β2-strand of the CTD in two distantly related bacterial COG0523s from Acinetobacter baumannii , ZigA and MigC. Thermodynamic and kinetic studies reveal that the Arg is analogous to the arginine finger motif of a Ras-cognate GAP, while the Lys residue appears to play a catalytic role in GTP hydrolysis. Cognate CTD added in trans to full-length RxK mutant ZigA or MigC rescues Zn(II)-activated GTPase activity whereas the noncognate CTD shows no rescue. The linker in Ab ZigA appears to gate Zn(II)-stimulated GTP hydrolysis. Solution NMR studies of RxK Ab MigC reveal that the two domains tumble independently of one another in the absence of bound ligands, with cognate CTD added in trans forming a tight complex. The extent to which conformational switching characterizes eukaryotic COG0523s is discussed.

GDF15 participates in epithelial cell senescence in radiation-induced lung injury through the ERK1/2-p16 signaling pathway

Objective Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy that can compromise treatment outcomes and reduce the quality of life of cancer patients. Cellular senescence is increasingly recognized as an important biological process in the development of RILI. This study aimed to identify senescence-associated molecules involved in RILI and to investigate their potential mechanisms of action. Methods Bioinformatics analysis was performed by integrating differential gene expression profiles from a RILI-related GEO dataset with a senescence-related gene set, which identified growth differentiation factor 15 (GDF15) as a candidate molecule of interest. A rat model of RILI was established, and inflammatory injury and fibrosis were evaluated by hematoxylin and eosin (HE) staining and Masson’s trichrome staining. DNA damage was assessed by γH2AX immunofluorescence. Senescence-associated changes were evaluated by senescence-associated β-galactosidase (SA-β-gal) staining and detection of p53, p21, p16, and GDF15 expression by Western blot. In addition, in vivo and in vitro experiments were performed to further explore the potential mechanism associated with GDF15 in radiation-induced epithelial senescence. Results Bioinformatics analysis identified GDF15 as a prominently upregulated senescence-related gene in RILI. In irradiated rat lungs, γH2AX expression was significantly increased, accompanied by inflammatory infiltration, fibrotic changes, and upregulation of senescence-associated markers. SA-β-gal staining further supported the presence of radiation-induced senescence in vivo. Similar findings were observed in irradiated BEAS-2B cells. Mechanistic experiments showed that GDF15 knockdown attenuated radiation-induced senescence and downregulated the expression of p-ERK1/2 and downstream p16, while ERK1/2 inhibition reduced senescence-associated β-gal staining and p16 expression. These findings suggest that radiation-induced GDF15 may contribute to epithelial cell senescence during RILI, potentially through the ERK1/2-p16 signaling pathway. Conclusion Our findings suggest that GDF15 is upregulated in response to ionizing radiation and may participate in epithelial cell senescence during the development of RILI. This process appears to be associated with the ERK1/2-p16 signaling pathway. These results provide additional insight into the molecular mechanisms underlying RILI and suggest that GDF15 may represent a potential target for future therapeutic intervention.

Multi-model analysis of the combined toxic effects of ultrafine carbon black and amisulbrom on A549 Cells

Subsarcomeric regulation of thin and thick filaments in skeletal muscle myofibrils

Muscle contraction relies on the coordinated activation of myosin motors from a folded-OFF state on the thick filament surface and their actin tracks on the thin filaments in response to calcium. Thick filaments contain distinct regulatory zones defined by the presence of myosin-binding protein C (MyBP-C) and titin super-repeats, but the control of myosin OFF/ON states within these zones has not been directly resolved. Here, we do so by fluorescence polarization microscopy (FPM) in myofibrils isolated from rabbit fast skeletal muscle. Using orientation-specific probes on myosin we show that folded-OFF motors are enriched in the MyBP-C–containing C zone in relaxed myofibrils, indicating that MyBP-C stabilizes the myosin OFF state in this filament domain. Under titin-based passive tension or partial calcium activation, active motors are enriched in the D zone at the filament tips, which lacks MyBP-C, suggesting that D-zone motors are activated at lower filament stress. Troponin probes further reveal that myosin enhances thin-filament activation in the region of filament overlap and drives the stress-dependent activation of the thin filament into adjacent nonoverlap regions. These findings uncover zone-specific control of myofilament activation within the sarcomere and establish FPM as a powerful tool for investigating disease-linked myofilament protein variants and therapeutic modulation.

A deep neural network and AIS-integrated method for ship trajectory prediction and yaw warning in cross-river power transmission line protection

Ship trajectory prediction plays a crucial role in ensuring the safety of inland waterway transportation and enabling intelligent scheduling. To address the limitations of traditional models in capturing long-term dependencies and extracting salient features, this study proposes a novel prediction model—TDV-TTCN-BiGRU—integrating a Temporal-Dependent Variable (TDV) attention mechanism with an improved TCN-BiGRU architecture. The model employs a hierarchical Temporal Convolutional Network (TTCN) to extract multi-scale temporal features in parallel, incorporates the TDV attention mechanism to adaptively adjust the weights of speed and heading features, and uses BiGRU to model bidirectional dependencies, thereby enhancing prediction accuracy and stability. Experiments based on real AIS data include both comparative and ablation studies. Results show that the proposed TCN-BiGRU outperforms CNN, BiGRU, CNN-BiLSTM, and CNN-BiGRU models, achieving the lowest prediction errors. Compared to CNN-BiGRU, the TDV-TTCN-BiGRU model reduces MSE of predicted longitude and latitude by 14.47% and 18.83%, respectively; MAE by 22.41% and 21.25%; and ADE by 21.46%, with trajectory plots showing closer alignment with actual vessel tracks. Furthermore, to address the risk of vessels deviating from navigable channels, a multi-level yaw warning mechanism is developed and validated in typical cross-river scenarios. The system achieves a warning accuracy of over 96%, significantly improving the responsiveness to unexpected yaw behavior. The proposed method provides technical support for intelligent ship navigation, maritime safety management, and the protection of overhead transmission lines.