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Editorial Note: The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA

Upper limb compensatory strategies across tasks with an ultrasound-controlled prosthesis

Systematic identification of microtubule lumen proteins reveals a taxane-sensitive luminal resident JPT2 regulating MEC17 accessibility

Microtubules have been extensively studied for their interactions at the outer surface and ends, yet the regulatory mechanisms within the microtubule lumen, particularly in singlet microtubules, remain poorly understood. Here, we developed a proximity-labeling strategy to distinguish intraluminal from external proteins, enabling the systematic identification of key regulators residing within the singlet microtubule lumen. Among these, we focused on Jupiter microtubule-associated homolog 2 (JPT2), a conserved microtubule-binding protein. JPT2 binds directly to microtubules and localizes to the lumen in a C-terminal-dependent manner. Within this compartment, it modulates the distribution of the α-tubulin acetyltransferase MEC17 and contributes to luminal homeostasis. Notably, the luminal accessibility of JPT2 is highly sensitive to microtubule structural states and is markedly reduced by Paclitaxel treatment, suggesting that drug-induced conformational changes or steric hindrance can restrict luminal entry. Together, our findings identify JPT2 as a key organizer of the singlet microtubule lumen and provide a framework for the spatial and functional analysis of microtubule inner proteins. Beyond exogenous perturbations, our observations suggest that luminal protein distribution may also be modulated by steric competition or selective entry among intraluminal components, indicating a more intricate regulatory landscape within the microtubule interior.

Correction: Layers of exposure risk management measures for the prevention and control of infections of healthcare workers treating COVID-19 patients

A-site dependent metastable polar phases from polarization compatible octahedral rotations in perovskite AZrO3 (A = Ca, Sr)

Dual-state stepwise methane-to-methanol conversion by water droplets with excellent yield and selectivity

Leveraging the continuous and rapid deposition and evaporation processes of water microdroplets on photocatalyst surfaces, this study presents an innovative dual-state stepwise methane conversion approach. This method significantly enhances the photocatalytic methane oxidation rate and selectivity, addressing the challenges of low methane solubility and poor liquid product selectivity typically found in aqueous-phase methane oxidation. By increasing the looping frequency per unit time, we achieved a state-of-the-art methane oxidation rate of 640 µmol g −1 h −1 using water as the sole oxidant, while maintaining approximately 95% selectivity toward liquid products, including 90% for methanol. This water microdroplet-assisted strategy not only establishes a framework for achieving both high yield and selectivity in photocatalytic methane oxidation but also pioneers a more efficient and sustainable approach for broadly applicable gases and water-involved photochemical conversion processes.

Spatial distribution and determinants of fertility preferences among female adolescents and young adults in Ethiopia

Introduction Understanding adolescents and young adults’ (AYAs) fertility preferences is crucial for guiding youth-focused family planning and predicting future fertility. However, fertility preference determinants and spatial patterns among Ethiopian AYAs remain underexplored. This study examines the spatial distribution and determinants of fertility preferences among female AYAs in Ethiopia. Methods We analysed the nationally representative 2016 Ethiopian Demographic and Health Survey, the most recent standard survey containing fertility preference data. Fertility preference was defined as the ideal number of children respondents would like to have over their lifetime. Negative binomial regression was used to assess associations between fertility preference and sociodemographic factors, while Bayesian model-based geostatistics was employed to predict the spatial distribution of fertility preferences. Sampling weights were applied to account for the complex survey design. Results A total of 5762 females aged 15−24 years were included in the analysis. The mean preferred ideal number of children among AYAs was 3.68 (95% confidence interval: 3.63, 3.74). Primary education (IRR: 0.91), higher education (Incidence Rate Ratio (IRR): 0.92), being unmarried (IRR: 0.86), and residing in large central areas (IRR: 0.90) were associated with a preference for fewer children. Being Muslim (IRR: 1.13), protestant (IRR: 1.17) and rural resident (IRR: 1.06) were associated with preference for more children. There was a significant spatial variation in fertility preferences. Respondents who resided in Somalia, Afar, and the western part of Gambella were found to have higher fertility preferences. The spatial regression analysis identified travel to a city (0.14, 95% Credible Interval (CI): 0.10, 0.18), urbanisation (−0.08 CI: −0.11, −0.05), income (−0.05; CI: −0.06, −0.04), and literacy (−0.06, CI −0.02, −0.01) were significant raster level predictors. Conclusion Fertility preferences among female AYAs varied by sociodemographic characteristics, with Somali, Afar, and western Gambella regions showing higher preferences. These findings emphasise the need for context-specific policies and programs that address regional, cultural, and educational disparities. Targeted interventions in rural and underserved regions, coupled with initiatives to enhance education, empower young women, are essential to support informed and autonomous reproductive decision-making among AYAs.

Experimental manipulation of ecological and cognitive conditions produces the entire conformity–diversity spectrum in a single species

Identifying the factors that drive individuals in a population to conform to the same behavior or to exhibit behavioral diversity is crucial for understanding collective decision-making, information transmission, and culture, yet remains challenging. Here, we propose and test a conceptual model predicting a population’s position along a conformity–diversity (CD) spectrum based on two key axes shaping the CD landscape: an ecological axis, representing competition over depleted resources, which favors diversity over conformity (since resources are depleted sooner if all individuals conform to the same resource type), and a cognitive axis reflecting the relative ease of learning a behavior socially versus individually. Our experiments show that manipulating these two primary factors is sufficient to produce the full CD spectrum within a single species. Specifically, studying socially foraging house sparrows, we manipulated competition using depleted or nondepleted feeding wells and manipulated the relative ease of learning a task individually by manipulating levels of experience and task difficulty. As predicted by the model, sparrows exhibited strong conformity under the combination of “no food depletion” and “difficult individual learning” conditions, strong diversity under the combination of “food depletion” and “easy individual learning” conditions, and intermediate levels of conformity under mixed conditions. The results show that a population’s position along the CD spectrum is highly flexible and sensitive to ecological and task-related conditions. Accordingly, the demonstrated CD surface may be viewed as an evolving reaction norm, and hence as a baseline over which additional factors shaping social conformity and differentiation can be tested.

Computational identification of epifriedelanol and derived analogs from Mikania cordata as potential HMG-CoA reductase inhibitors

Hypercholesterolemia, a major risk factor for cardiovascular diseases, arises from elevated blood cholesterol levels and remains a global health concern. The limitations of current therapies underscore the need for alternative drugs from natural sources. Mikania cordata (Asteraceae) is an ethnomedicinally important species that harbors numerous bioactive phytoconstituents. In this study, 91 phytocompounds of this medicinal species were virtually screened targeting the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase protein. Molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and MM/GBSA (molecular mechanics/generalized born surface area) analyses identified epifriedelanol as the best lead candidate among the phytocompounds with strong binding affinity (−8.6 kcal/mol), drug-likeness, and free binding energy (−39.5 kcal/mol), outperforming the standard drug atorvastatin (−7.7 kcal/mol and −21.4 kcal/mol). Analogs of epifriedelanol (EA) were further explored, generating 451 compounds. High-throughput screening of these analogs identified 244 compounds with a docking score higher than atorvastatin (−7.7 kcal/mol). The ADMET evaluation highlighted two analogs, EA2 and EA3, with docking scores of −9.3 kcal/mol and supportive MM/GBSA free energies (−31.9 and −43.7 kcal/mol). Molecular dynamics simulation (500 ns) confirmed the structural stability of epifriedelanol, EA2, and EA3, while essential dynamics and Gibbs free energy landscape analyses indicated a binding behavior comparable to that of atorvastatin. Target class analysis predicted interactions with nuclear receptors. These findings suggest that epifriedelanol and its analogs are promising natural leads against hypercholesterolemia, warranting further in vitro and in vivo validation.

Frustrated random-singlet state with ice-type structural fluctuation in spinel titanates

In ice, it is well known that the orientation of H 2 O molecules is disordered by geometrical frustration. Ice-analogous materials having a pyrochlore lattice display interesting phenomena such as the spin-ice state and the magnetic monopole. In the spinel titanate MgTi 2 O 4 , the Ti ions have a quantum spin in the pyrochlore lattice. The Ti ions are displaced, accompanied by the spin-singlet formation. Since this displacement pattern follows the ice rule, the title compound is a material analogous to ice. When a small quantity of Ti ions are replaced with Mg ions, the ice-type structural fluctuation exists. In this structural ice-type state, the spins are also fluctuating at a nanosecond scale down to 0.3 K. We ascribed this phenomenon to the gapless frustrated random-singlet state, in which the spin-singlet pairs are resonating, and the orphan spins are hopping.

Correction: Effects of dysmenorrhea on work productivity and quality of life in Japanese women: A large-scale web-based cross-sectional study

Intrinsic OASL expression governs heterogeneity in interferon induction during influenza A virus infection

Effective control of viral infection requires rapid induction of the innate immune response, especially the type I and type III interferon (IFN) systems. Despite the critical role of IFN induction in host defense, numerous studies have established that most cells fail to produce IFNs in response to viral stimuli. The specific factors that govern cellular heterogeneity in IFN induction potential during infection are not understood. To identify specific host factors that license some cells but not others to mount an IFN response to viral infection, we developed an approach for analyzing temporal scRNA-seq data of influenza A virus (IAV)-infected cells. This approach identified the expression of several interferon stimulated genes (ISGs) within preinfection cells as correlates of IFN induction potential of those cells, postinfection. Validation experiments confirmed that intrinsic expression of the ISG OASL is essential for robust IFNL induction during IAV infection. Altogether, our findings reveal an important role for intrinsic expression of ISGs in promoting IFN induction and provide insights into the mechanisms that regulate cell-to-cell heterogeneity in innate immune activation.

Patient death and nurses’ coping strategies: Perception of nurses at a tertiary referral hospital in Kenya

In healthcare facilities, patient deaths are a common occurrence, exposing nurses to diverse behavioral and emotional reactions, particularly within the context of resource constraints in Kenyan healthcare settings. This study aimed to investigate the experiences of nurses at AIC Kijabe Hospital in Kenya regarding patient death and their coping strategies. The focus group discussions sought to understand factors influencing nurses’ reactions to death, assessing the adequacy of their basic training in preparing them for coping, exploring the determinants of their coping strategy choices, and gathering recommendations for enhancing coping mechanisms. Employing qualitative research, six focus group discussions were conducted with 50 nurses from various hospital departments, including the emergency department, medical and surgical wards, intensive care unit, and maternity ward. After data collection, the information was transcribed verbatim and analyzed using a thematic analysis approach with inductive coding. Two researchers independently coded the data. A code was an identifying term for a specific part with emphasis on the aspect being investigated. Subsequently, the research team met to compare the codes and reached a consensus on the best interpretation of the data codes. The coding was then categorized into themes and Subthemes. The study findings revealed four overarching themes: individual process, institutional process, work team relationships, and educational gaps. In the individual process, nurses disclosed factors influencing their reactions to and feelings about death, encompassing Stress injuries, views of life (pessimism or optimism), cultural background, religious beliefs, and self-drive/self-management. Nurses expressed immediate emotional responses to the word “death” and conveyed the emotional toll of losing patients. The institutional process delved into how the hospital assisted nurses in coping with patient deaths, revealing a lack of support or guidance in selecting coping mechanisms. Nurses advocated for psychological support, support groups, and counseling sessions. Work relationships and educational gaps were also featured, with nurses emphasizing the deficiency in training on the emotional and psychological aspects of coping with death. They advocated for enhancements in educational preparation to better equip nurses for the emotional challenges intrinsic to their profession.

Circular RNA–based therapy targeting metabolic vulnerability of fatty acid synthesis overcomes castration-resistant prostate cancer

Androgen receptor (AR) signaling is essential for prostate cancer (PCa) cell growth and remains a key therapeutic target in castration-resistant PCa (CRPC). While circular RNAs (circRNAs) are increasingly recognized as important regulatory molecules, their roles in AR signaling during PCa progression remain poorly understood. This study identified circUTRN , an AR-inhibited circRNA that is upregulated following neoadjuvant hormonal therapy and downregulated in PCa tissues. circUTRN inhibits proliferation in both castration-sensitive and castration-resistant PCa. Mechanistically, circUTRN binds to acetyl-CoA carboxylase 1 (ACC1) and impairs the activity through both phosphorylation-dependent and independent pathways, thereby disturbing de novo fatty acid synthesis. The dynamic relation between circUTRN and ACC1 expression during PCa progression from treatment-naïve to therapeutic-resistant states highlights the metabolic vulnerability of fatty acid synthesis. Notably, we developed nanoparticles to deliver circUTRN in combination with AR signaling inhibitors (ARSIs). This approach effectively suppressed CRPC xenograft tumor growth, even in models resistant to next-generation ARSIs. This study reveals an AR-regulated circRNA involved in PCa progression and suggests a potential therapeutic strategy for treatment-resistant PCa.

Correction: Nummi Digitali: A pioneering multimodal platform for numismatic heritage

NFE2L1/Nrf1 forms a coactivator complex post-peptide: <i>N</i> -glycanase-mediated sequence editing and mitigates proteasome dysfunction

Nuclear factor erythroid 2-like 1 (NFE2L1/Nrf1), an endoplasmic reticulum (ER)-associated transcription factor, is responsible for the coordinated expression of proteasome subunit genes upon proteasomal dysfunction. N -glycosylated proteins undergo protein sequence editing by peptide: N -glycanase (NGLY1)-mediated conversion of N -glycosylated asparagine residues to aspartic acid. Nrf proteins are the only transcription factors that undergo sequence editing for transcriptional activation. However, the mechanism via which sequence editing regulates the transcriptional activity of Nrf1 has remained unclear. Here, we demonstrated that sequence editing of the ninth N -glycosylation site (Asn574) in human Nrf1 is required for proteasome gene expression in HeLa cells. Editing of Asn574 is essential for interaction with host cell factor C1 and O -GlcNAc transferase, which is required for Nrf1 chromatin binding and sufficient proteasome expression. Furthermore, sequence editing of N -glycosylation sites other than Asn574 is required for the interaction with the coactivator CREBBP/EP300, thereby enhancing Nrf1’s transcriptional activity. Unexpectedly, the expression of Nrf1 mutants that mimic proteolytic processing by DNA-damage-inducible 1 homolog 2 and sequence editing by NGLY1 markedly diminished the growth rate in HeLa cells, suggesting that the constitutive activation of Nrf1 exhibits cytotoxicity. Collectively, our study explains the strategy of on-demand Nrf1 activation for survival benefits. Nrf1 is synthesized as a proteasome-targeting protein and is highly glycosylated in the ER. Nrf1 is activated via sequence editing-dependent coactivator complex formation only when the proteasome needs to be compensated for.

Retraction: Molecular and cellular mechanisms of cigarette smoke-induced myocardial injury: Prevention by Vitamin C

Nucleic acid base pair open states by hydrogen exchange

Nucleic acid base pair open states that are actively driven to expose normally hidden sequences and host reactions with processing proteins have been highly studied. However, the spontaneous natural base pair opening behavior of native duplexes is still not understood. Hydrogen exchange (HX) experiments can measure the kinetic and equilibrium parameters of base pair opening reactions, but different approaches have led to discrepant datasets and opposing views of nucleic acid structural dynamics. Here, I reexamine the data and resolve these long-standing contradictory views. The conclusion is that the seemingly contradictory datasets characterize two different modes of base pair opening reactions that, for identifiable reasons, are selectively accessed by the different methods and molecular models used. H-T exchange of DNA, duplex RNA, and long synthetic duplexes is dominated by large multi-base-pair openings with reclosing times of milliseconds (kcl ~20/sec) and surprisingly high population (Kop ~10 −2 ). H-H exchange measured by NMR relaxation is limited to the study of small rapidly tumbling oligonucleotides. Their HX is dominated by single base pair openings with reclosing times of microseconds and extremely low population (Kop ~10 −6 ). The different openings are seen selectively by the different methods because small oligonucleotides cannot host the extensive openings, while in large polynucleotides, the minimal population of single base pair openings makes no perceptible contribution to measured HX. The unexpected kinetics, equilibrium occupation, and size of DNA base pair openings are suggestive of rapidly migrating traveling loop wave packets known as solitons that dynamically scan and expose candidate recognition sites.

Economic burden of drought using the life satisfaction approach: A case study of slum dwellers in southeast Iran

Drought is one of the most visible effects of climate change and poses significant challenges for sustainable development. Assessing the costs of drought is essential for effective policymaking, and indirect costs are likely to provide a more comprehensive estimate. This descriptive-analytical study was conducted in 2023 among households in the slum areas of Kerman, a city in southeastern Iran. Given the population’s diversity, a cluster sampling method was employed, and data were collected from 507 households through a questionnaire. The research team estimated the Ordinary Least Squares (OLS) model, the Marginal Rate of Substitution (MRS), and Willingness to Pay (WTP) using the life satisfaction approach. The results indicated that 38.42% of households identified drought as the primary reason for their migration, while 33.27% were formerly smallholder farmers or agricultural workers. Notably, farmers and ranchers reported significantly lower life satisfaction levels. The MRS for these households was −0.570, underscoring the negative impact of drought on their income. Furthermore, based on their income, their willingness to pay for drought mitigation was estimated at $1,968.98 per household, reflecting their economic constraints. Overall, the modeling results from the life satisfaction approach indicate that drought imposes a significant economic burden on households, particularly smallholders and agricultural workers. The forced migration to the slum areas of Kerman, driven by declining agricultural potential viability, has not produced stability but has instead led to ongoing economic instability and reduced life satisfaction.

<i>Legionella</i> effector Ceg10 acetylates RPS20 to inhibit host translation and induce cell cycle arrest

Legionella pneumophila , the causative agent of Legionnaires’ disease, utilizes a type IV secretion system (T4SS) to translocate effectors into host cells, modulating diverse cellular processes to create a replication-permissive niche. Here, we characterize Ceg10, a T4SS-translocated effector, as a nucleus-targeting acetyltransferase that interferes with host ribosome biogenesis and cell cycle progression. Structural analysis reveals that Ceg10 harbors a conserved Cys-His-Asp (CHD) catalytic triad required for its acetyltransferase activity. Upon nuclear import mediated by the host transport adaptor HEATR3, Ceg10 selectively acetylates the ribosomal protein RPS20 at Thr64, Thr65, and Arg66, which have not been annotated as posttranslational modification sites. This acetylation impairs RPS20’s interaction with RPS29 and 18S rRNA, two components critical for 40S ribosomal subunit assembly, leading to translation inhibition and G1/S cell cycle arrest. These host perturbations are essential for efficient early-stage intracellular replication of L. pneumophila . Our findings identify a distinct mechanism by which a bacterial effector co-opts nuclear import machinery and directly modifies ribosomal proteins to subvert host biosynthesis and cell cycle control, highlighting ribosomal protein acetylation as a hitherto unrecognized role in host–pathogen interactions.