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Identification of compounds that repress DUX4 expression in facioscapulohumeral muscular dystrophy

Circular and athermal atmospheric CO ₂ capture by food waste-derived amyloid sorbents

Food waste contributes substantially to global CO 2 emissions, yet it also offers underutilized opportunities for climate change mitigation within and beyond the food system. Direct air capture technologies can help offset these emissions, but most current sorbents are synthetic, energy-intensive, and poorly aligned with circular-economy principles, while bio-based alternatives typically feature low CO 2 capacity and poor stability. Here, we upcycle proteins recovered from dairy and tofu waste streams into functional amyloid fibril microbeads for ambient CO 2 capture. Atomic-level design and templated molding enable lysine and glutamine residues within the fibrils, along with hydroxyl groups introduced by mild KOH treatment, to form abundant active sites for CO 2 capture, achieving up to 2.20 mmol g −1 under ambient air, and 2.51 mmol g −1 under simulated air (oxygen-free). The microbeads are regenerated within 10 to 12 min via alternating dilute acid–alkali mist without any thermal input and remain stable over 30 cycles. Life cycle assessment, ranking efficiency product, and techno-economic analysis reveal superior sustainability and cost efficiency compared with conventional sorbents, validating a circular economy approach that upcycles food waste into CO 2 sorbents, which can, if needed, ultimately be reintegrated into the food system.

Benchmark of biomarker identification and prognostic modeling methods on diverse censored data

The practices of identifying biomarkers and developing prognostic models using genomic data has become increasingly prevalent. Such data often features characteristics that make these practices difficult, namely high dimensionality, correlations between predictors, and sparsity. Many modern methods have been developed to address these problematic characteristics while performing feature selection and prognostic modeling, but a large-scale comparison of their performances in these tasks on diverse right-censored time to event data (aka survival time data) is much needed. We have compiled many existing methods, including some machine learning methods, several which have performed well in previous benchmarks, primarily for comparison in regards to variable selection capability, and secondarily for survival time prediction on many synthetic datasets with varying levels of sparsity, correlation between predictors, and signal strength of informative predictors. For illustration, we have also performed multiple analyses on a publicly available and widely used cancer cohort from The Cancer Genome Atlas using these methods. We evaluated the methods through extensive simulation studies in terms of the false discovery rate, F1-score, concordance index, Brier score, root mean square error, and computation time. Of the methods compared, CoxBoost and the Adaptive LASSO performed well in all metrics, and the LASSO and elastic net excelled when evaluating concordance index and F1-score. The Benjamini-Hoschberg and q-value procedures showed volatile performances in controlling the false discovery rate. Some methods’ performances were greatly affected by differences in the data characteristics. With our extensive numerical study, we have identified the best performing methods for a plethora of data characteristics using informative metrics. This will help cancer researchers in choosing the best approach for their needs when working with genomic data.

Investigation of damage evolution in asphalt concrete under coupled ultraviolet aging and freeze-thaw cycles

Abstract To clarify the degradation law of crack resistance of asphalt concrete under the coupled action of UV aging and freeze–thaw cycles, semi-circular bending tests were conducted on unaged and UV-aged specimens subjected to varying numbers of freeze–thaw cycles. Key parameters, including air void content, flexural tensile strength, flexural stiffness, failure displacement, and fracture energy, were measured, and their effectiveness in characterizing coupled damage was evaluated using a damage index and correlation analysis. The results indicate that increasing freeze–thaw cycles lead to a gradual rise in air void content, accompanied by continuous reductions in flexural tensile strength, pre-peak fracture energy, and total fracture energy, demonstrating a significant deterioration in internal compactness and crack resistance. Under identical freeze–thaw conditions, specimens exposed to combined UV aging and freeze–thaw effects exhibit higher air void content and further reductions in strength and fracture energy compared to those subjected to freeze–thaw cycles alone, indicating that UV aging exacerbates freeze–thaw damage. Although flexural stiffness shows an overall decreasing trend, coupled-damage specimens maintain relatively higher values than unaged specimens, reflecting the stiffening effect induced by UV aging. Damage index analysis identifies flexural tensile strength as the most sensitive indicator of both freeze–thaw and coupled damage, followed by fracture energy and air void content. Correlation analysis reveals a general negative relationship between air void content and major crack-resistance indices, while flexural tensile strength shows a strong positive correlation with pre-peak fracture energy. Overall, flexural tensile strength and pre-peak fracture energy are recommended as key indicators for evaluating the evolution of crack resistance under coupled environmental effects.

The Urban Pulse: Diagnosing the urbanization process as spiky, cyclical, and asynchronous

Many urban indicators predominantly focus on static outcomes, failing to capture the dynamic nature of urbanization. Here, we introduce the concept of the Urban Pulse to characterize urbanization as a process of continual spatiotemporal change. Using dense time series remote sensing data, we operationalize the Urban Pulse for six cities that represent diverse development levels, economies, and geographies: Seattle, Shenzhen, Lagos, Mumbai, Dubai, and Mexico City. We then use the Urban Pulse to assess how COVID-19 affected each of the six cities. The results empirically substantiate three major insights. First, urbanization is inherently spiky, characterized by episodic events that deviate from baseline trends. Second, urbanization is cyclical, reflecting transitions through stages of expansion, stabilization, or decline, and does not occur with predictable frequency, such as seasonal patterns. Third, urbanization is asynchronous, with subcity areas exhibiting uncoordinated development patterns. The Urban Pulse COVID-19 analysis shows that while urbanization processes for some cities have not returned to prepandemic patterns, other cities exhibit a significant shift in patterns postpandemic. These findings suggest that the selection of a neighborhood or subcity area as an observation unit may have little bearing on a city as a whole. By capturing these spatial and temporal rhythms, the Urban Pulse framework provides a comprehensive understanding of process dynamics, enabling researchers to link processes to outcomes more effectively. This approach allows for the recognition of early warning signals at subcity scales and may facilitate targeted interventions at the neighborhood level, where they are most impactful.

The evolution of life size Barbie and Ken: Are they any closer to reality?

Barbie and Ken dolls have been criticized over time for their overt misalignment of body shape in comparison with the average adult, and the possibility that this impacts the formative minds of children, particularly girls. Updating a previous examination of the original Barbie and Ken dolls from 1996, this study compared the body measures of the 2016 “Fashionista” range—including Curvy, Petite, Tall, and Standard Barbie models, and new Malibu Ken—with representative population data of young adult females and males using anthropometric techniques. A range of anthropometric girth measures plus height were taken from each doll, and body proportions were calculated. The rules of allometry were used to scale the dolls to a standardized adult height of 170.18 cm to determine the dimensions the dolls at this adjusted size. The dimensions were then compared to the same height-adjusted reference population norms used in the original study. The comparison revealed significant alterations in the dolls’ morphology compared with the original Barbie and Ken, with key measures of waist-to-hip and chest-to-waist ratios becoming more realistic and falling within the 95% confidence range of the population. According to z-score deviation data, Curvy Barbie fell closest to the mean for most of the scaled girth measures, while new Ken was closer to the mean for all girths except ankle. Design changes reflect a shift toward greater body diversity, with potential benefits for children’s health behaviours through the production of a broader range of more diverse, human-like dolls. Importantly, key measurements and body proportions were generally closer to the respective reference populations.

A 5mC-related gene signature predicts prognosis and therapy response in hepatocellular carcinoma

Dysregulation of autophagosome–mitochondria contacts contributes to autophagy dysfunction and neurodegeneration in tauopathy

Mitochondria (Mito) engage in extensive communication with other organelles through membrane contacts. Perturbed mitochondria–organelle interactions are indicated in a variety of neurodegenerative diseases, but the underlying mechanisms remain poorly understood. Here, we report a class of mitochondria–organelle communication: autophagosome/autophagic vacuole (AV)–Mito contact, which exhibits hypertethering in tauopathy neurons, consequently hampering AV retrograde transport. Such defects are attributed to accelerated turnover of the contact release factor TBC1D15, triggered by mitochondrial bioenergetic deficit-induced hyperactivity of the adenosine monophosphate-activated protein kinase (AMPK). Increasing TBC1D15 levels or repressing AMPK activity normalizes AV-Mito contact release and restores retrograde transport of AVs, thereby increasing autophagic cargo clearance and reducing tau burden in tauopathy axons. Furthermore, overexpression of TBC1D15 enhances autophagic clearance and attenuates tau pathology, alleviating neurodegeneration and cognitive dysfunction in tauopathy mice. Taken together, our study provides mechanistic insights into AV-Mito contact dysregulation in tauopathy-related autophagy failure, laying the groundwork for the development of potential therapeutics to combat tauopathy diseases.

Factors associated with low-level viremia in people living with HIV: A 10-year retrospective study in South Korea

Purpose The goal of antiretroviral therapy is to achieve and sustain the suppression of human immunodeficiency virus (HIV) viral load. In this study, we aimed to identify risk factors for low-level viremia (LLV) and examine their association with clinical outcomes in South Korea. Methods We retrospectively reviewed the medical records of patients with human immunodeficiency virus infection registered at Seoul Medical Center and Hallym University Sacred Heart Hospital between 2014 and 2023. LLV was defined as at least two consecutive HIV RNA measurements of 40–199 copies/mL taken more than 4 weeks apart. Patients with LLV were compared with those who maintained virological suppression (viral load < 40 copies/mL). Results Of the 381 patients included in the analysis, 15 (3.94%) experienced LLV. Compared with patients who maintained virological suppression, patients with LLV more frequently had an initial viral load ≥ 500,000 copies/mL ( P  < 0.01). No significant differences were observed between the groups in the rates of virological rebound, new-onset acquired immune deficiency syndrome–defining conditions, or mortality. Multivariable logistic regression identified an initial viral load ≥ 500,000 copies/mL as an independent risk factor for LLV (adjusted odds ratio, 4.735; 95% confidence interval, 1.505–14.897). Conclusion A high viral load was a significant risk factor for LLV. Large multicenter studies are required to further investigate risk factors and clinical implications of LLV in people living with HIV.

Area-adjusted influence of built-up pattern on urban land surface temperature in an arid landscape

Functional asymmetry and essential structural roles of PDE6α and PDE6β subunits in rod–photoreceptor integrity

Tetrameric rod phosphodiesterase-6 (PDE6), comprised of an α/β heterodimeric catalytic core and two inhibitory γ subunits, critically regulates cyclic GMP (cGMP) levels in rod photoreceptors. While the rod-PDE6 catalytic core is a heterodimer, the cone isoform is an α′/α′ homodimer. This structural difference suggests a unique role for each rod subunit. Due to the lack of heterologous expression systems, we generated four transgenic mouse models to examine the functional contributions of the N-terminal pony-tail (Pt)-motifs and of the catalytic domains of the individual catalytic subunits of rod PDE6 in vivo. We generated two N-terminal deletions (PDE6αΔ2-48AA and PDE6βΔ2-46AA); and two active-site mutations (PDE6αH599A and PDE6βH597A) designed to selectively abolish catalytic activity. Native mass spectrometric analysis of heterozygous mice revealed that only wild-type enzyme was produced. While homozygous mutations in all lines caused complete photoreceptor degeneration, analysis of heterozygous lines revealed a disproportionately greater impact of β-subunit mutations on protein stability, enzymatic activity, and visual function. These findings establish that both active subunits are essential for rod integrity, but a significant functional asymmetry exists within the PDE6αβ heterodimer. Our results demonstrate that the PDE6β subunit plays a more dominant role in maintaining the structural and functional pool of PDE6 enzyme.

Outcomes of school-aged children following traumatic brain injury from road traffic accidents in Malaysia: A retrospective study

Background Traumatic brain injury (TBI) resulting from road traffic accidents (RTAs) is a leading cause of morbidity in children globally. However, paediatric TBI outcomes are understudied in Southeast Asia. Objective To examine functional outcomes and associated factors among school-aged children with RTA-related TBI in Malaysia. Methods This retrospective study analysed medical records of 542 children aged 7–17 years with first-time TBI from RTAs. Data on sociodemographics, injury characteristics, complications, and outcomes were collected. The subjects’ reports were grouped into three categories for analyses: young children (7–9-year-olds), adolescents (10–14-year-olds) and older adolescents (15–17-year-olds). Functional status was assessed using the Glasgow Outcome Scale–Extended for Paediatrics (GOS-E Peds), and reported as good (category 1 and 2) or poor (category 3–8) outcomes. Descriptive statistics and multivariate logistic regression were used. Results The majority of children were male (81.5%) with a mean age of 14.3 years. Motorcycles were the predominant accident mode (76.0%) especially among adolescents and older adolescents. The mean duration between the RTAs and report review was 20.7 ± 14.9 months. Only 27.5% of the children achieved good functional outcomes. Young children had the highest rate of recovery (34.5%), though not statistically significant. Among older adolescents, mild TBI significantly increased the odds of a good outcome (OR=2.5; 95% CI: 1.29–4.83; p  = 0.007), while tracheostomy was strongly associated with poor outcomes (OR=7.02; 95% CI: 2.06–23.93; p  = 0.002). Despite high rate of return to education, a significant proportion of children faced academic challenges post-brain injury. Conclusion Motorcycles remain the primary mode of RTA-related TBI among Malaysian children, particularly among adolescents. There was no significant difference in outcomes between the three age groups, although the young children had the highest rate of recovery. A substantial proportion of the children experience ongoing functional and academic difficulties despite returning to school. This highlights the need for coordinated clinical, educational, and policy responses in settings with limited paediatric rehabilitation infrastructure.

Construction and validation of a nomogram for overall survival prognosis in patients with advanced (stage III/IV) pancreatic cancer

Targeting the cGAS–STING pathway mitigates Huntington disease pathogenesis in a knock-in mouse model

Cyclic GMP–AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), form a key cytosolic DNA-sensing pathway that drives innate immune activation and proinflammatory signaling. We previously showed that cGAS is upregulated in Huntington disease (HD) cellular models, where it regulates autophagy and inflammation; however, its in vivo role remained unclear. Here, we genetically ablated cGAS in Q175DN knock-in HD mice and performed longitudinal behavioral assessments from 2 to 14 mo of age. cGAS deletion significantly improved HD-associated motor deficits, including rotarod performance and beam-walk coordination, and mitigated progressive body-weight loss. Histological analyses revealed reduced lateral ventricle enlargement and decreased striatal astrogliosis and microgliosis. While minimal effects were observed in wild-type littermates, transcriptomic profiling of HD brains lacking cGAS showed downregulation of genes involved in development and cell–cell communication, along with upregulation of genes linked to ion transport and synaptic function. Lipidomic analysis further demonstrated increased levels of immunoregulatory lipids, particularly 12-HETE and 12-HEPE, indicating a shift toward a protective lipid profile. Importantly, pharmacological inhibition of STING using H-151 improved age-dependent motor performance, reduced striatal atrophy, and attenuated glial cell activation in Q175DN mice. Collectively, these findings identify the cGAS–STING pathway as a critical driver of HD progression and support its inhibition as a promising therapeutic strategy.

Correction: Intravenous thrombolysis for acute central retinal artery occlusion: Protocol for a systematic review and individual participant data meta-analysis of randomized controlled trials

6-gingerol attenuates renal interstitial fibrosis by downregulating PI3K/Akt/mTOR signaling pathway in unilateral ureteral obstruction rats

Reply to Xiao and Imada: Prosociality across group boundaries is possible without partner choice

The experiences of doctors in Lesotho during the COVID-19 pandemic: A qualitative study

The COVID-19 pandemic dramatically increased pressure on healthcare staff who were trying to manage and adjust to the novel situation. For many healthcare workers, this came at a cost to their wellbeing. However, as research is predominantly focused on the Western world, less is known about the experiences of healthcare staff in places such as Africa. Using qualitative interviews, this study investigated the experiences of seven doctors in Lesotho regarding their wellbeing during the pandemic. Through interpretative phenomenological analysis, five themes were identified: under pressure, unprepared and out of control; constant uncertainty and threat; isolation and connection; attempts to cope independently and new perspectives. These results indicate that these doctors experienced multiple challenges whilst working during the pandemic which extended beyond the work environment and negatively impacted their wellbeing. Despite this, they experienced support from friends, family and colleagues, found ways to support themselves, and found points of learning from the experience. Implications for how doctors are supported at a national and local level are discussed. Further research should continue to explore doctors’ wellbeing in relation to any long-term implications of the COVID-19 pandemic and during more typical work.

Characterization of gut microbiota in wild Asian elephants (Elephas maximus) from five forests across Thailand

Structural modeling reveals the mechanism of motor ATPase coordination during type IV pilus retraction

Diverse bacterial species utilize surface appendages called type IV pili (T4P) to interact with their environment. These structures are dynamically extended and retracted from the cell surface, which is critical for diverse functions. Some T4P systems rely on two distinct motor ATPases, PilT and PilU, whose combined activities are required to power forceful T4P retraction. However, the mechanism by which these motors coordinate to facilitate T4P retraction has remained unclear. Here, we utilize the competence T4P in Vibrio cholerae as a model system to elucidate the molecular basis for PilT–PilU coordination during T4P retraction. Specifically, we modeled the interactions between PilT and PilU using AlphaFold 3 and molecular dynamics (MD) simulations. We then empirically tested these models using a combination of cytological and high-resolution genetic approaches. Our results reveal that interactions between PilT and the PilU C-terminus are critical for these motors to coordinate to drive T4P retraction. Finally, we show that PilT–PilU interactions are broadly conserved in T4P systems from diverse bacterial species, and we experimentally validate that they are required for T4P retraction in Acinetobacter baylyi . Together, this work expands our fundamental understanding of T4P dynamics, and more broadly it provides mechanistic insight into how these ATPases coordinate to assemble some of the strongest biological motors in nature.