Browse Articles

A human-specific long noncoding RNA regulator of antigen-presenting cell viability and antimicrobial defense

Macrophages are essential for both, to clear pathogens and preserve tissue homeostasis, yet the molecular regulators of this equilibrium remain incompletely defined. Here, we identify SAILR (survival associated immune-regulatory RNA), a primate-specific long noncoding RNA (lncRNA), as a critical modulator of macrophage viability under infection conditions. SAILR is induced during monocyte-to-macrophage differentiation, but rapidly downregulated upon bacterial challenge in a nuclear factor kappa B (NF-κB) dependent manner. In both naïve and immune-activated macrophages, SAILR dampens the expression of adhesion, phagocytosis, and invasion factors, which include SIGLEC1 and MMP7. During infection with Salmonella Typhimurium, depletion of SAILR sensitizes macrophages to apoptosis, resulting in loss of intracellular replication niches and reduced bacterial recovery. Conversely, enforced SAILR expression promotes macrophage survival and increases intracellular pathogen burden. Mechanistically, SAILR interacts with the antiapoptotic adaptor protein 14-3-3β to support macrophage survival. Notably, downregulation of SAILR is mirrored in circulating immune cells from patients with severe COVID-19 and sepsis. Together, our findings position SAILR as a central regulator in linking macrophage survival to host–pathogen interaction and disease pathophysiology.

Effect of intentional daily liter of plain water on total fluid and caloric intake among free-living adults

While previous studies have examined short-term water consumption and corresponding energy intake, few have investigated the effects of a longitudinal intervention in non-obese, young adults. We aimed to evaluate the effect of a 6-week daily liter of plain water consumption on fluid and caloric intake among free-living healthy adults. Thirty-eight young healthy adults (25 ± 6 y, 1.67 ± 0.09 m, 73.0 ± 16.7 kg, 25.8 ± 4.2 of body mass index) were provided two 500mL bottles of water per day and asked to consume them for six weeks. They were provided no further direction on fluid consumption during the study. Participants recorded 24-hour total food and fluids consumed and collected urine across three time points of baseline, 3-week (mid), and 6-week (post). Twenty-four-hour total fluid, plain water, sugar-sweetened beverages, caloric intake, urine specific gravity (USG), urine osmolality (U osm ), and urine volume were measured at all three time points. Hydration status was assessed via 24-hour USG and U osm . Twenty-four-hour total fluid intake was significantly increased at mid (p = .040) but not post (p = .426). Twenty-four-hour total plain water intake was significantly increased at mid (p = .028) and post (p = .049) time points. No significant differences were observed in 24-hour total sugar-sweetened beverage intake across time points (p = .210). Twenty-four-hour total caloric intake was significant reduced at the post (p = .048) but not at mid (p = .257). Twenty-four-hour total caloric intake was not associated with 24-hour total fluid intake (r = .052, p = .618), total plain water intake (r = −.049, p = .636), and total sugar-sweetened beverages intake (r = .143, p = .170). No significant differences were found in 24-hour USG (p = .075) and total urine volume (p = .491) among time points, but U osm significantly decreased at mid (p = .001). In conclusion, a moderate increase in plain water intake may prompt a decrease in daily caloric intake and thus facilitate weight management.

Integrating multi-source geoscience data with RF-weighted conditional variational autoencoders (CVAE) for porphyry copper prospectivity mapping: an application to the Ardestan district, Central Iran

IL-7–glucose–Aiolos axis orchestrates pathogenic CD8 ⁺ T cell function in spondyloarthritis

CD8 + T cells are essential mediators of host defense, whereas their aberrant activation contributes to inflammatory diseases such as spondyloarthritis. The molecular mechanisms governing human CD8 + T cell effector programming remain incompletely understood. Here, we identify a metabolically distinct subset of human CD8 + T cells defined by high expression of CXCR3, IL-7R, and GLUT1 and low expression of the transcription factor Aiolos. IL-7–JAK–STAT signaling was associated with increased GLUT1 expression and glucose uptake, accompanied by reduced Aiolos expression in CD8 + T cells. Consistent with this, Aiolos functioned as a regulatory constraint on effector cytokine production under glucose-limited conditions, and its reduction was associated with enhanced cytokine production in metabolically active CD8 + T cells. Circulating CD8 + T cells from patients with spondyloarthritis exhibited elevated GLUT1 expression compared with rheumatoid arthritis and healthy controls, which correlated with disease activity. In addition, CXCR3 + IL-7R + pSTAT5 + GLUT1 + Aiolos low CD8 + T cells were enriched in inflamed joints, where CXCL10 may contribute to their recruitment. Increased FDG uptake in inflamed sacroiliac joints further supports enhanced metabolic activity at sites of inflammation. JAK inhibitor therapy was associated with reduced GLUT1 expression and increased Aiolos expression in CD8 + T cells, accompanied by decreased effector cytokine production and clinical improvement in patients with spondyloarthritis. Together, these findings support a model in which cytokine signaling, metabolic state, and transcriptional regulation are functionally linked in human CD8 + T cells, and suggest that Aiolos may act as a regulatory node integrating these inputs in inflammatory diseases.

Standard precautions versus clinically triggered contact precautions for prevention of extended-spectrum β-lactamase-producing enterobacterales in acute-care geriatric units: A prospective non-inferiority interventional study protocol (GERSP-study)

Introduction Extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) pose a major global public health challenge, as they are associated with frequent empirical antibiotic treatment failure and increased patient morbidity and mortality. In this context, contact precautions (CP) have traditionally been recommended for hospitalized patients colonized or infected with ESBL-E to prevent healthcare-associated transmission. However, growing evidence has questioned the effectiveness of this strategy in certain care settings. The primary objective of this study is to assess the non-inferiority of standard precautions (SP) compared with clinically triggered CP in reducing the incidence density of ESBL-E acquisition in acute-care geriatric wards. By doing so, this study aims to inform the evaluation of pragmatic infection prevention policies implemented at the institutional level in vulnerable hospital populations. Methods and analysis We will conduct a prospective, two-site interventional study in two geriatric departments of the Metz–Thionville Regional Hospital Center (Metz, France) using an alternating-period (crossover-like) design at the site level, with random allocation of the starting condition (CP first vs SP first). Patients will be screened for ESBL-E carriage at admission and at discharge. During CP periods, contact precautions are implemented only for patients with clinically detected ESBL-E infections identified through routine clinical cultures; asymptomatic ESBL-E carriage identified through surveillance screening does not trigger contact precautions. During SP periods, patients are managed using SP alone. The primary outcome is the incidence density of ESBL-E acquisition per 1,000 patient-days. Secondary objectives include species-specific analyses comparing ESBL-producing Escherichia coli and non-E. coli Enterobacterales. The total inclusion period is four years. Incidence rates will be compared using count regression models adapted to clustered period-based data.

Single pass inactivation of airborne multidrug resistant bacteria using electron beam irradiation with mechanistic evidence

Neural circuits for stress-induced water drinking in relief of anxiety

Drinking water is a rapid, instinctive behavior of mammals following stress. The role of such stress-induced water drinking behavior and its neural mechanisms remain poorly known. Here, we identify two sequentially activated neural circuits that respectively mediate stress-induced drinking behavior and reward encoding, which collectively promote the extinction of anxiety-like behaviors in mice. Specifically, mild short-term stress induces anxiety-like behaviors and activates glutamatergic neurons in the medial prefrontal cortex (mPFC Glu ) projecting to glutamatergic neurons in the median preoptic nucleus (MnPO Glu ), consequently driving drinking behavior in mice. This drinking behavior subsequently activates GABAergic neurons in the MnPO (MnPO GABA ), which then inhibit GABAergic neurons in the ventral tegmental area (VTA GABA ), leading to disinhibition of reward-encoding dopaminergic VTA neurons (VTA DA ), ultimately mediating the extinction of stress-induced anxiety-like behaviors. The present study defines cortical–hypothalamic–midbrain connections underlying the anxiety-relieving effects of drinking behavior, providing a circuit basis for innate stress coping strategies.

Editorial Note: Optimization of cold chain logistics distribution path considering traffic condition and replenishment along the way

Semantic edge detection of fractures in geological outcrops using edge aware dilated convolutional networks

Abstract Natural fracture networks govern subsurface fluid flow, rock-mass stability, and strain accommodation in the brittle crust, yet their automated delineation from outcrop imagery remains challenging due to multi-scale size variability, low contrast between fracture boundaries and host-rock texture, and scene clutter from vegetation, shadows, and blast artifacts. Standard encoder-decoder networks apply fixed-size receptive fields that inadequately span the fractal-like scale range of natural discontinuity networks, while gradient-based classical detectors lack the semantic context required to suppress non-structural scene edges. We introduce GeoFractNet : a dilated U-Net coupling ConvNeXt encoder blocks with multi-scale dilated convolutions ( $$d \in \{1,\!2,\!4,\!8\}$$ ), gated edge-aware skip connections fusing Scharr and Gabor filter responses, and a Sobel Edge-Aware (SEA) Loss that directly penalizes gradient misalignment at fracture boundaries. The model output is a binary semantic edge map (per-pixel classification of fracture-boundary pixels versus background) rather than a vectorized fracture trace network; conversion to discrete trace objects requires subsequent post-processing. Trained on GeoCrack , an open-access fracture edge dataset of 12,158 annotated patches from 49 structurally and lithologically diverse outcrops across five countries, GeoFractNet achieves mIoU  $$= 0.91$$ , Dice  $$= 0.92$$ , and Boundary F $$_1 = 0.90$$ , outperforming all evaluated classical and deep-learning baselines. Compared to the best performing network in literature, YOLACT++, GeoFractNet reduces false positives by 38% and recovers 94% of long-range fracture edges missed by classical (Canny) edge detection on a curated hard-negative evaluation subset (420 patches containing vegetation, blast holes, and strong illumination gradients). Ablation studies confirm that the gated edge-aware skip connections and SEA Loss provide the largest incremental gains in boundary-sensitive metrics, with no architectural component degrading performance at any ablation step. Code, model weights, and the GeoCrack dataset are openly released, providing a reproducible benchmark for automated fracture characterization in structural geology, geomechanics, and reservoir analogue studies.

Expression of Concern for Raghuvanshi et al., <i>Mycobacterium tuberculosis</i> evades host immunity by recruiting mesenchymal stem cells

Do China’s low-carbon technology products and environmental goods trade mitigate energy-related carbon emissions in Africa?

Motivated by the rise in green trade between China and Africa and the growing environmental pressures associated with energy-related emissions in Africa, this study examines the impacts of low-carbon technology (LT) products and environmental goods (EGs) imported from China on the energy-related carbon emissions intensity (CEI) of 42 African countries for the period 2003–2023. To account for endogeneity issues and distributional differences, the study employs instrumental variables and panel quantile techniques. The findings reveal several important points. First, LT products and EGs imported from China significantly reduce the energy-related CEI of African countries. Second, the influence of imports of LT products and EGs on energy-related CEI varies by income level: they increase energy-related CEI in low-income African economies but decrease it in middle-income African nations. Third, the import of LT products and EGs has a stronger energy-related CEI-reducing effect in African countries with better institutional frameworks. These findings contribute to the current literature by offering a detailed and nuanced understanding of how trade in LT products and EGs can help reduce energy-related carbon emissions. Policy recommendations are presented based on these findings.

Integrating multi-proxy geochemistry and machine learning to decode cretaceous palaeoenvironments and tectonic evolution in the Nigerian Middle Benue Trough, West Africa

Environmental phylogenetics supports a steady diversification of crown eukaryotes starting from the mid-Proterozoic

Molecular clock and preservation of early microfossil assemblages suggest that eukaryotes were present and already diverse more than ~1600 million years ago (Ma). Yet, the earliest identifiable eukaryotic crown group fossil only appeared around 1050 Ma, leaving a ~600 My gap in the Mesoproterozoic during which the evolution and diversification of early eukaryotes remain poorly understood. Here, we infer a timeline of eukaryote evolution using molecular clock and birth–death diversification models, including the large diversity of environmental sequences to take into account the uncultured majority of microbial life. Our analyses, based on a unique dataset of 75,975 nonredundant Operational Taxonomic Units and 77 well-supported fossil calibrations, indicate a steady diversification of crown group eukaryotes during the Proterozoic after the Last Eukaryotic Common Ancestor. We show that Archaeplastida was one of the earliest diversifying supergroups and the most diverse throughout the Proterozoic, suggesting that the first successful plastid endosymbiosis gave Archaeplastida a measurable evolutionary advantage. Discoba, Amoebozoa, and Rhizaria followed Archaeplastida in phylogenetic diversity throughout the Proterozoic, indicating that crown eukaryotes were already thriving in this Era. These results contrast with the common view that the geologically stable Proterozoic Era experienced little eukaryotic evolutionary innovation and indicate that all current supergroups were already established in the Mesoproterozoic.

The effect of COVID-19 and socioeconomic inequalities on emergency department accesses for psychiatric conditions

Background COVID-19 produced a detrimental effect on mental health that could not be appropriately addressed due to a reduced accessibility of healthcare services, as patients with socioeconomic vulnerabilities faced the largest barriers in accessing healthcare during the pandemic. This study aimed to investigate emergency department (ED) accesses with a psychiatric diagnosis before and after COVID-19, with a specific focus on the role of socioeconomic factors. Methods This is a multicentre longitudinal retrospective study that involves a population-based open cohort of residents and National Health Service (NHS)beneficiaries aged ≥ 10, enrolled in three large Italian areas from 1 January 2018 to 31 December 2021 (n = 5,159,363). The primary outcome of interest was the First Mental Health Emergency Access (FMHEA); sex, age, deprivation level, citizenship and groups of diagnosis were considered as covariates. Crude incidence rates were calculated comparing the two time periods (pre- and post-COVID-19) by each covariate. In the context of interrupted time series (ITS), incidence rate ratios (IRR) of FMHEAs with 95%CI were estimated via an ITS analysis using a step-change negative binomial model. Temporal trend of FMHEAs was investigated through an ITS analysis on their monthly numbers. Results During follow-up, 56,762 FMHEAs were observed. The multivariate analysis showed that before COVID-19, the rate of FMHEA was higher among the highly deprived (IRR: 1.28; 95%CI:1.22.-1.35 for highest vs lowest deprivation level), females, people aged ≤24 and ≥85 and immigrants. A significant interaction between the COVID-19 period and deprivation level was found: the probability of reduced FMHEA increased with the deprivation level. The greater impact of COVID-19 was found in the central age classes resulting in a reduction in the differences in FMHEA rates by age in the post-Covid-19 period. Conclusion COVID-19 reduced incidence rates of ED accesses, but increased socioeconomic inequalities in the use of ED for mental health disorders.

Vitamin D3 reverses intestinal epithelial cell injury in septic rats by alleviating toll-like receptor 4 mediated endoplasmic reticulum stress

Whistleblowers can contain the unethical externalities of human–AI delegation

Prior work using controlled principal-agent experiments suggests two risks from delegating tasks to AI systems: Human principals are more likely to request profit-maximizing misconduct from AI agents than from human agents, and AI agents are more likely to comply. Here we test whether third-party observers can contain the resulting harm. In an incentivized die-reporting paradigm, principals instructed either a human or an AI agent how strongly to prioritize profit over accuracy, creating potential financial harm to a charity. We first confirm, with human principals ( N = 600) and three large language models as AI agents, that delegation to AI produces larger negative externalities than delegation to humans. We then study observers who could pay a personal cost to flag a principal’s instruction, canceling the principal’s gain in favor of the charity, as a laboratory analogue of whistleblowing. In this observer study ( N = 300), the probability of flagging increased with how unethical the principal’s request was, but did not depend on whether the request was directed to a human or an AI agent. Because principals made more unethical requests under AI delegation, flagging was more frequent under AI delegation. When combined with agent behavior, this increase in flagging fully neutralized the negative externalities of AI delegation in our experimental setting. These findings support institutional protections for whistleblowers as one potential organizational safeguard against the harms of human–AI delegation.

The duration of nutrient limiting conditions can contribute to shaping subsequent diatom community composition: Insights from laboratory experiments

Climate-driven increases in global surface water temperatures are enhancing upper ocean stratification and likely resulting in more prolonged periods of nutrient limitation. Although nutrient limitation in diatoms and their growth responses to increasing temperatures have been studied extensively, much less is known about their growth response to nutrient injection after prolonged durations of nutrient limitation. This study examines the growth response of three bloom-forming diatom species: Pseudo-nitzschia pungens , P. australis , and Skeletonema costatum after short-term (~2 week) and prolonged (~4 week) periods of nutrient limitation at five temperatures (9, 12, 15, 20, and 25°C). Pseudo-nitzschia species showed shorter lag times and higher specific growth rates than S. costatum after prolonged nutrient stress. These findings demonstrate that certain diatom species can exhibit faster growth recovery after prolonged nutrient limitation and in warmer conditions compared to others, providing new insights on drivers that shape phytoplankton communities.

Correction: The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans

Productivity gains and work conditions in coercive labor markets: Experimental evidence from the Bangladesh brick sector

Productivity growth in competitive labor markets can improve worker welfare over time through higher wages or better conditions, but it is unclear if productivity gains benefit workers in coercive labor markets (where force or threats shape employment). We examine this issue in the Bangladesh brick sector using a randomized trial that introduced a more efficient production method. Despite large productivity improvements, we find no reduction in (high) rates of labor trafficking or child labor. These findings suggest that in the short-term, productivity growth alone may be insufficient to improve work conditions in coercive settings.

Distinct gut and oral microbiome patterns associated with dyslexia in a family-based cohort: A preliminary exploratory study

Background Many neurodevelopmental disorders, including dyslexia and childhood apraxia of speech (CAS), have genetic predispositions that are understood to varying degrees. However, the microbiome in individuals with dyslexia and CAS remains underexplored. The goal of this exploratory study was to determine whether fecal and saliva microbiome diversity and composition are associated with dyslexia or CAS. Methods To this end, we examined the fecal and saliva microbiota of individuals with dyslexia, CAS, and their neurotypical family members using 16S rRNA gene amplicon sequencing in a family-based cohort composing of 7 individuals with dyslexia, 11 with CAS, and 10 neurotypical family members (n = 28). Participants with dyslexia and CAS were drawn from separate families, with neurotypical relatives serving as within-family controls. A total of 19 fecal and 29 saliva samples were collected, with paired fecal-saliva samples available for 19 individuals. Taxonomic classification was performed using four 16S rRNA reference databases, and microbial diversity, composition, and functional potential were analyzed. Results Individuals with dyslexia consistently showed distinct fecal microbiome alpha and beta diversity patterns at the species level compared to neurotypical family members and participants with CAS histories, irrespective of taxonomic database employed. Both fecal and saliva datasets identified key taxa associated with dyslexia, but not with CAS. Predicted functional profiling further identified dyslexia-associated pathways in the fecal microbiome, whereas no functional differences were detected in saliva. Conclusion Although these results suggest that individuals with dyslexia may harbor distinct fecal and saliva microbiomes, the findings are exploratory and should be considered as hypothesis-generating. Future studies leveraging larger, independent cohorts will be essential to validate these findings and to more rigorously examine the oral-gut-brain axis in language-based syndromes.