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Transcriptional regulation of thorn tip sclerification in plants

A common characteristic of thorns, prickles, and spines is a hardened and sharp tip. This feature complicates cultivation and postharvest processing for many crops, yet the molecular mechanisms governing this specific sclerification process remain unclear. By genome editing screening, we identified a MYB family gene named S HORT and S OFT T HORN 1 ( SST1 ) that specifically promotes the development of sclerenchyma cells at Citrus thorn tips. CRISPR-Cas9 editing of SST1 results in the formation of short and soft thorns with significantly reduced secondary wall thickening at the tips, while leaving stem growth unaffected. SST1 directly activates NST1 and SND1 , driving a hierarchical transcriptional regulatory network for secondary wall biosynthesis. Moreover, SST1 homologs in various species are specifically expressed in thorns, suggesting a potential conserved role. Our results uncover the molecular basis for hard plant protective structures, and modulation of this pathway could be an effective strategy for optimizing cultivation practices.

Muscle fatigue assessment using surface electromyography in farm operations performed in protected cultivation

Analysis and forecast of hand, foot, and mouth disease epidemic trends in Guangzhou, China, 2013–2023

Hand, foot, and mouth disease (HFMD) primarily affects children under the age of five and has emerged as a significant public health concern in China. This study examines HFMD incidence trends across various gender and age demographics in Guangzhou from 2013 to 2023, providing a comprehensive overview to inform future prevention and management strategies. Utilizing epidemiological data from the National Notifiable Infectious Disease Reporting Information System, we employed Joinpoint regression modeling to assess variations in incidence rates among different demographic cohorts and developed a Seasonal Autoregressive Integrated Moving Average (SARIMA) model to analyze case trends and project future occurrences. The findings revealed biennial peaks and notable seasonality, indicating cases across all age groups, though predominantly among children under five. Joinpoint regression analysis demonstrated a significant decrease in incidence rates for children younger than one year (Average Annual Percent Change [AAPC]=−13.50%, P < 0.001) and those aged one year (AAPC = −10.35%, P = 0.002), while incidence remained stable for children aged two to five years. Conversely, a significant upward trend was identified in children aged six years and older (AAPC = 13.09%, P = 0.019). Gender-specific trends closely resembled these overall patterns, with both males and females experiencing similar percentage changes in incidence rates. The SARIMA model indicates a projected decline in HFMD cases for 2024, followed by a phase of relative stability characterized by minor fluctuations. These results offer crucial insights into HFMD trends, illustrating the effectiveness of current preventive measures in reducing incidence among younger children while underscoring the necessity for targeted interventions to address the rising trends in older age groups. By leveraging these findings, health authorities can refine control strategies and prioritize public health responses to effectively mitigate HFMD outbreaks.

The multimodal transcriptional response of denervated skeletal muscle involves regulation of <i>Gramd1</i> genes impacting muscle size

The development and maintenance of the neuromuscular junction (NMJ) requires reciprocal signals between the nerve terminals and multinucleated skeletal muscle fibers (myofibers). This interaction drives highly specialized transcription in the subsynaptic or NMJ myonuclei within mature myofibers leading to clustering of acetylcholine receptors (AChRs). Here, we utilized single-nucleus RNA sequencing (snRNA-seq) to delineate the transcriptional response of myonuclei to denervation. Through snRNA-seq on skeletal muscle from two independent mouse models of denervation, sciatic nerve transection and amyotrophic lateral sclerosis, we identify a multimodal transcriptional response of NMJ-enriched genes and an alteration in cholesterol homeostasis in myofibers. Gramd1 , a family of genes involved in nonvesicular cholesterol transport, are enriched at the NMJ in innervated muscle and upregulated in both models of denervation by the NMJ and extrasynaptic myonuclei. In vivo gain and loss of function studies indicate that Gramd1 genes regulate myofiber sizes. Mechanistically, we did not detect obvious changes in AChR clustering due to Gramd1 knockdown but revealed a role in autophagy after denervation. We uncovered a dynamic transcriptional response of myonuclei to denervation and highlight a critical role for Gramd1 to maintain myofiber sizes.

Enhanced multi objective graph learning approach for optimizing traffic speed prediction on spatial and temporal features

Application of machine learning models in predicting physical literacy in 4–6-year-old children: A comprehensive analysis of individual and family factors

Physical literacy in children has become a significant research topic in both education and psychology. Recently, machine learning, as a cutting-edge AI technology, has started to play a crucial role in these fields. This study aimed to apply machine learning models to predict physical literacy in 4–6-year-old children and to comprehensively analyze the influence of individual and family factors. We evaluated the physical literacy of 1,734 children aged 4–6 and systematically examined the impact of both individual factors (such as gender, age, body type, sedentary behavior, screen time, moderate-to-vigorous physical activity (MVPA), sleep duration, and sleep quality) and family factors (such as parents’ education level, occupation, exercise frequency, support for children’s physical activity, household annual income, and family exercise environment) using various machine learning models. Results showed that the ensemble learning model achieved the best performance in predicting physical literacy, with an AUC of 86.2%. Among all predictive factors, mother’s exercise frequency, family exercise environment, and time spent on MVPA were identified as the most important. These findings provide new insights into enhancing children’s physical literacy and underscore the critical role of family environment and lifestyle in its development.

Genetic dissection of nonconventional introns reveals codominant noncanonical splicing code in <i>Euglena</i>

Pre-mRNA splicing is essential for eukaryotic gene expression and is achieved through the accurate recognition of exon–intron boundaries. Although nonconventional introns, which do not follow the conventional GT-AG splicing rule, have been identified in several species, these introns are typically rare in any given genome. Here, we demonstrate the widespread occurrence of nonconventional introns (71.8% of all introns) in the Euglena agilis genome and identify consensus motifs at these nonconventional exon–intron boundaries. We assessed the splicing efficiency of nonconventional introns and variants with point mutations via genomic knock-in within the second exon of Glucan synthase-like 2 in Euglena gracilis and genetically defined the sequence signature (5′-N 3 CDG-/-CH′GN 5–6 |R exon -3′) required for their proper splicing. This signature is present in 61.2% of all nonconventional introns detected in the E. agilis genome. Accordingly, we present a noncanonical splicing code for Euglena introns, highlighting the global coexistence of dual splicing rules for conventional and nonconventional introns.

Retraction Note: Identification of RNA processing factor LSM5 as a new adverse biomarker in nasopharyngeal carcinoma

Associations of SARS-CoV-2 PCR positivity with clinical symptoms and race/ethnicity: The household transmission study

Objective The objective of this study was to identify demographic and clinical factors associated with SARS-CoV-2 infection among household contacts (HCs) following exposure to a confirmed case. Methods We analyzed an existing case-ascertained prospective cohort study of 43 HCs of SARS-CoV-2-positive index cases recruited from Stanford Health Care between March 2020 and June 2022. Participants self-collected nasal swabs daily for up to 21 days for reverse transcription polymerase chain reaction (RT-PCR) testing and reported symptoms in daily diaries. Using Cox proportional hazards models, we assessed associations between participant characteristics over time to first positive PCR result. Results We found that symptomatology and race/ethnicity were independently associated with increased infection risk. In multivariable analysis, participants with systemic symptoms had a higher likelihood of testing positive (adjusted hazard ratio [aHR]=2.62; 95% confidence interval [CI]: 1.38–6.55). Additionally, identifying as a racial/ethnic minority had a greater risk of a positive test (aHR = 2.55 for systemic symptoms, 2.43 for any respiratory symptoms, and 2.40 for upper respiratory symptoms) compared to white patients. Conclusion These findings underscore the importance of symptom-based surveillance and highlight ongoing racial and ethnic disparities in SARS-CoV-2 transmission risk. This study also demonstrates the feasibility of longitudinal, self-administered testing and offers a scalable model for investigating transmission dynamics of respiratory viruses in community settings.

Structural and functional analysis of the <i>Mycobacterium tuberculosis</i> MmpS5L5 efflux pump presages increased bedaquiline resistance

Bedaquiline, an antitubercular drug that targets ATP-synthase, is a key component of a new oral drug regimen that has revolutionized the treatment of multidrug-resistant tuberculosis. Clinical bedaquiline resistance in Mycobacterium tuberculosis has rapidly emerged, primarily due to mutations in the transcriptional repressor Rv0678 that result in upregulation of the resistance-nodulation-division (RND) efflux pump MmpS5/MmpL5 (MmpS5L5). Here, to understand how MmpS5L5 effluxes bedaquiline, we determined the structure of the MmpS5L5 complex using cryo-electron microscopy, revealing a trimeric architecture distinct from the canonical tripartite RND efflux pumps of gram-negative bacteria. Structure prediction modeling in conjunction with functional genetic analysis indicates that it uses a periplasmic coiled-coil tube to transport molecules across the cell wall. Structure-guided genetic approaches identify MmpL5 mutations that alter bedaquiline transport; these mutations converge on a region in MmpL5 located in the lower portion of the periplasmic cavity, proximal to the outer leaflet of the inner membrane, suggesting a route for bedaquiline entry into the pump. While currently known clinical resistance to bedaquiline is due to pump upregulation, our findings that several MmpL5 variants increase bedaquiline efflux may presage the emergence of additional modes of clinical resistance.

Role of human collaboration in artificial intelligence with fuzzy based mathematical models and decision making problems

Assessment of frailty in patients with advanced chronic kidney disease, and the role of microvesicles: A single-center study

Background Frailty is a highly prevalent syndrome in patients with advanced age and chronic diseases, and it is associated with atherothrombotic pathologies, suggesting a procoagulant state in these patients. Circulating microvesicles (cMVs), are small phospholipid-rich vesicles, which have been shown to participate in atherothrombotic onset and progression. We aim to analyze frailty in patients with advanced chronic kidney disease (CKD), and to determine the role of microvesicles in this population. Materials and methods We conducted a prospective cohort study with 85 patients with advanced CKD. Our main objective was to evaluate frailty and its novel association with circulating microvesicles in advanced CKD. To define frailty, Fried’s five criteria were used and we obtained blood for cMVs analysis by flow cytometry. Results The prevalence of frailty in patients with advanced CKD was 27% (CI 95% 17-37%). We found that risk factors for frailty were age (OR 1.06; CI 95% to 1.11; p=0.027), type 2 diabetes mellitus (OR 5.77; CI 95% to 18.9; p=0.004) and hemoglobin (g/dL) (OR 0.63; CI 95% to 0.94; p=0.023). Total cMVs, platelet derived cMVs and endothelial derived cMVs were significantly higher in frail patients. In the predictive multivariable binary logistic regression model over frailty, three predictors explain 41% of the variability of frailty (Nagelkerke square R = 0.41; p &lt;0.001) with the following contribution: T2DM (19%), total cMVs (14%) and hemoglobin (8%). Discussion Frailty is highly prevalent in patients with advanced CKD. Although we still do not know in depth the mechanisms involved in frailty, to our knowledge this is the first study that links cMVs and frailty in patients with advanced CKD. In our opinion it could be explored as a good biomarker or therapeutic target in advanced CKD.

Muscle-specific increased expression of <i>JAG1</i> improves the skeletal muscle phenotype in dystrophin-deficient mice

Therapeutic strategies for Duchenne muscular dystrophy (DMD) will likely require complementary approaches. One possibility is to explore genetic modifiers that improve muscle regeneration and function. The beneficial effects of the overexpression of Jagged-1 were described in escaper golden retriever muscular dystrophy (GRMD) dogs that had a near-normal life and validated in dystrophin-deficient zebrafish. To clarify the underlying biology of JAG1 overexpression in dystrophic muscles, we generated a transgenic mouse (mdx 5cv - JAG1 ) model that lacks dystrophin and overexpresses human JAG1 in striated muscles. Skeletal muscles from mdx 5cv - JAG1 and mdx 5cv mice were studied at 1-, 4-, and 12-mo time points. JAG1 expression in mdx 5cv - JAG1 increased by 3 to 5 times compared to mdx 5cv . Consequently, mdx 5cv - JAG1 muscles were significantly bigger and stronger than dystrophic controls, along with an increased number of myofibers. Proteomics data show increased dysferlin in mdx 5cv - JAG1 muscles and an association of the histone methyltransferase Nsd1 with the phenotype. Our data support the positive effect of JAG1 overexpression in dystrophic muscles.

Impact of urban density on human well-being and sustainable development in Delhi, India

Abstract Achieving sustainable urban development amid rapid urbanization requires a deep understanding of how urban density influences human well-being. This study examines the spatial relationship between built-up population density (BUD) and human well-being across Delhi, one of the world’s fastest-growing megacities. Using a combination of high-resolution census data, remote sensing, and spatial analysis, the study identifies markedly uneven urban form characterized by extreme density variation, ranging from 2,884 to 136,385 persons per km² across clusters, and uncoordinated development, particularly in peripheral zones. While BUD significantly affects well-being outcomes, the analysis reveals that beyond an optimal threshold, socio-economic conditions become equally influential. The findings emphasize the urgent need for differential planning strategies: promoting infrastructure and planned densification in low-density peripheries; encouraging mixed-use development in moderate-density zones; and alleviating congestion while enhancing services in high-density, unplanned areas. These insights provide a policy framework aligned with the Sustainable Development Goals, particularly Goal 11, which aims to make cities inclusive, safe, resilient, and sustainable. By emphasizing the spatial heterogeneity of urban density and its implications for well-being, this research provides a valuable lens for urban policy and planning in rapidly growing global cities.

Gain modulation of probabilistic selection without synaptic relearning

Adaptation of behavior requires the brain to change goals in a changing environment. Synaptic learning has shown its effectiveness in changing the probability of selecting actions based on their outcome. In the extreme case, it is vital not to repeat an action to a given goal that led to harmful punishment. The present model proposes a simple neural mechanism of gain modulation that makes possible immediate changes in the probability of selecting a goal after punishment of variable intensity. The results show how gain modulation determines the type of elementary navigation process within the state space of a network of neuronal populations of excitatory neurons regulated by inhibition. Immediately after punishment, the system can avoid the punished populations by going back or jumping to unpunished populations. This does not require particular credit assignment at the ‘choice’ population (the branching node) but only modulation of the gain of units active at the time of punishment (at the end of the punished branch). In this way, gain modulation encodes memories of past experiences that change behavior without modification of synaptic efficacies. This neuronal non-synaptic learning mechanism does not require statistical relearning. It helps the system not repeat harmful choices that may lead to further punishments. Thus, such a neuronal learning mechanism can complement synaptic plasticity.

ALKBH5 demethylates the m ⁶ A modification of SOCS3 in microglia/macrophages and alleviates neuroinflammation after brain injury

Microglia/macrophage-induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6-methyladenosine (m 6 A) RNA modifications in this process remains elusive. Single-cell RNA sequencing (scRNA-seq) and m 6 A RNA immunoprecipitation sequencing (MeRIP-seq) across multiple time points postinjury revealed a strong correlation between m 6 A modifications and genes enriched in microglia/macrophages. Furthermore, the m 6 A demethylase ALKBH5 was identified as a key regulator of dynamic m 6 A patterns at the injury site. ALKBH5 suppression in microglia/macrophages exacerbated neuroinflammation in vitro and worsened neurological deficits in controlled cortical impact (CCI) models. MeRIP-qPCR and RNA pull-down assays revealed SOCS3 was a downstream target of ALKBH5-mediated m 6 A demethylation. This demethylation stabilized Socs3 mRNA and enhanced its protein expression, which in turn suppressed neuroinflammation via inhibiting the JAK2-STAT3 pathway. Conversely, SOCS3 depletion impaired functional recovery after injury. These findings unveiled a critical ALKBH5–m 6 A–SOCS3 regulatory axis that mitigated microglia/macrophage-driven neuroinflammation after TBI, underscoring its potential as a therapeutic intervention target for TBI progression.

Murraya koenigii methanolic extract inhibits bacterial growth and biofilm of Staphylococcus aureus and Enterococcus faecalis

The BiteBarrier transfluthrin emanator demonstrates significant protection against susceptible and resistant malaria and arbovirus vectors in semi-field trials in Tanzania

Controlling mosquito-borne diseases is becoming increasingly challenging due to factors such as insecticide resistance and shifts in mosquito behavior. The increasing proportion of early evening, morning, and outdoor biting reduces the effectiveness of core interventions like bed nets, which mainly protect people while sleeping indoors. In response, spatial emanators that release volatile active ingredients into the surrounding air to reduce human-vector contact offer a scalable, complementary strategy. This study evaluated the impact of BiteBarrier, a transfluthrin-based spatial emanator, over eight weeks of aging against multiple mosquito species in a semi-field system simulating both indoor and outdoor settings. We assessed the protective efficacy using both landing rate and feeding success methods across five mosquito species, including pyrethroid susceptible Anopheles gambiae sensu stricto (s.s.) and Aedes aegypti; An. gambiae s.s. with knock down resistance (KDR); and pyrethroid resistant An. funestus and Culex quinquefasciatus with upregulation of mixed function oxidases. The results show that the feeding endpoint provides more robust estimates of protective efficacy compared to the landing endpoint. The BiteBarrier provided over 93% (95% CI: 92–93) protection indoors and 80% (95% CI: 78–81) outdoors against mosquito bites and substantial mortality 47% (95% CI: 43–53) indoor and 26% (95% CI: 22–30) outdoors, regardless of mosquito species or resistance status. Overall, the BiteBarrier shows potential as a tool for reducing mosquito bites and vectorial capacity, offering protection over at least eight weeks of use for both indoor and outdoor environments.

Within-country inequality and the shaping of a just global climate policy

Climate policy design must balance emissions mitigation with concerns for fairness, particularly as climate change disproportionately affects the poorest households within and across countries. Integrated Assessment Models used for global climate policy evaluation have so far typically not considered inequality effects within countries. To fill this gap, we develop a global Integrated Assessment Model representing national economies and subnational income, mitigation cost, and climate damage distribution and assess a range of climate policy schemes with varying levels of effort sharing across countries and households. The schemes are consistent with limiting temperature increases to 2 °C and account for the possibility to use carbon tax revenues to address distributional effects within and between countries. We find that carbon taxation with redistribution improves global welfare and reduces inequality, with the most substantial gains achieved under uniform taxation paired with global per capita transfers. A Loss and Damage mechanism offers significant welfare improvements in vulnerable countries while requiring only a modest share of global carbon revenues in the medium term. The poorest households within all countries may benefit from the transfer scheme, in particular when some redistribution is made at the country level. Our findings underscore the potential for climate policy to advance both environmental and social goals, provided revenue recycling mechanisms are effectively implemented. In particular, they demonstrate the feasibility of a welfare improving global climate policy involving limited international redistribution.

A machine learning analysis for hybrid nanofluid flow between two co-axial cylinders