Scarlet fever, caused by group A streptococcus (GAS), has resurged globally since the early 2010s. Although schools and pre-schools are well acknowledged as the high-risk settings for scarlet fever outbreaks, little is known about the effect of school terms on scarlet fever epidemics among pre-school-aged and school-aged children. In this study, we aimed to understand the role of school terms in scarlet fever epidemics by leveraging a population-based surveillance across 15 years in China. We included weekly scarlet fever cases from 2005 to 2019 in Liaoning Province (one of the provinces with highest incidence of scarlet fever) among children aged ≤ 12 years who were subsequently categorised into three groups: school-attending, pre-school-attending, and non-pre-school-attending. We used wavelet spectrum analysis to identify periodicity patterns of scarlet fever epidemics. We applied negative binomial regression models to estimate the relative risk (RR) of scarlet fever associated with school terms and population categories, adjusting for background risk of infection, meteorological factors, and temporal trends. A total of 64,950 scarlet fever cases were identified, with non-pre-school-attending children, pre-school-attending children and school-attending children accounting for 16%, 44%, and 40%, respectively. Scarlet fever exhibited a significant semi-annual pattern, usually peaking in May to June (during the spring semester) and November to December (during the autumn semester), with substantial declines during school breaks. Wavelet analysis identified this strong semi-annual signal, plus an additional 3.3-year (171-week) periodicity signal. Compared to non-pre-school-attending children during school breaks, school term was associated with a 2-fold higher risk of scarlet fever in pre-school-attending children (relative risk [RR] 2.14, 95% confidence interval [CI] 1.94-2.36) and school-attending children (RR 2.07, 95% CI 1.88-2.27), whereas a reduced risk was observed in non-pre-school-attending children (RR 0.84, 95% CI 0.77-0.91). During school breaks, pre-school-attending children remained at higher risk than non-pre-school-attending children (RR 1.80, 95% CI 1.63-1.99), while school-attending children showed no significantly increased risk (RR 0.97, 95% CI 0.88-1.08). Further stratification by school semester indicated that the association between school term and scarlet fever risk for pre-school-attending children and school-attending children was stronger in the autumn semester than in the spring semester. School terms have differential effects on scarlet fever risk across population categories. School-attending children have a higher risk for scarlet fever during school terms while pre-school-attending children have a higher risk for scarlet fever all year round than non-pre-school-attending children. By contrast, the risk decreases among non-pre-school-attending children during school terms. These findings support the development of targeted public health interventions to mitigate scarlet fever outbreaks in high-incidence regions.
The ABC transporter Scarlet is known for its role in pigment deposition within insect eye pigment granules. However, its extraocular functions remain largely unexplored. To investigate the role of Scarlet(LOCMI17149) in olfactory modulation and its regulatory mechanisms in the brains of the migratory locusts. The expression patterns and functions of scarlet(LOCMI17149) were analyzed by quantitative PCR (qPCR), fluorescence in situ hybridization and RNAi knockdown. Enzyme linked immunosorbent assay (ELISA) was employed to measure xanthurenic acid (XA) titers. Pharmacological interventions were performed to validate the role of XA and scarlet(LOCMI17149) in multi-unit electrophysiology. DNA-RNA immunoprecipitation (DRIP), chromatin immunoprecipitation (ChIP) and qPCR were conducted to measure the levels of R-loop and histone modification. Among the four Scarlet orthologs, one scarlet(LOCMI17149) is predominantly expressed in the antennae and brain. This expression pattern implicates its roles in olfactory processing. RNAi knockdown of scarlet(LOCMI17149) impaired olfactory preference for plant volatiles and common odorants (indole and β-ionone). This behavioral deficit caused by scarlet(LOCMI17149) RNAi knockdown is linked to a metabolic shift, characterized by decreased 3-hydroxykynurenine (3-HK) and elevated levels of its metabolite XA in the brain. Intracerebral injection of XA recapitulates the olfactory impairment and implicates it as a key behavioral effector. Local field potential (LFP) and electroantennogram (EAG) analysis support that XA suppresses the neurophysiological activity in the antennae and brains of locusts. Furthermore, we discover that an R-loop structure (Scarlet-RL) forms at scarlet(LOCMI17149) locus. Knockdown of Scarlet-RL with antisense oligonucleotides (ASO) increases scarlet(LOCMI17149) mRNA expression, indicating that Scarlet-RL acts as a transcriptional repressor in scarlet(LOCMI17149) transcription. Scarlet-RL mediates the synthesis of nascent mRNAs through histone modification. This study provides the first evidence that Scarlet-RL directly controls the transcription of this chemosensory regulator, revealing a novel epigenetic mechanism that orchestrates insect olfactory preference.
This study investigated the epidemiological and spatiotemporal characteristics of scarlet fever in Guangzhou, China, and provided a scientific basis for the formulation and optimization of prevention and control strategies. The epidemiological profile of scarlet fever was systematically reviewed using descriptive analysis. We used the Moran's I, local indicators of spatial association, and the retrospective spatiotemporal scanning statistical analysis to study the spatiotemporal aggregation phenomenon of scarlet fever in Guangzhou. From 2005 to 2024, 9,601 scarlet fever cases were reported within Guangzhou, with an annual average morbidity of 3.16 per 100,000. Joinpoint regression analysis indicated a statistically significant overall upward trend in scarlet fever incidence (AAPC = 17.26%, p < 0.001), characterized by four phases: low-incidence phase, upsurge phase, COVID-19-affected phase and post COVID-19 rebound phase. Seasonal distribution exhibited a dual-modal pattern, and the crest of transmission occurred from April to June and November to the following January. Demographically, cases mainly occurred among males and kindergarten children aged 3-6 years. Notably, during the post COVID-19 rebound phase, the proportion of cases among students, particularly those aged 7-10 years, increased substantially, becoming a major affected group nearly comparable to kindergarten children. Spatially, higher incidence was observed within central urban districts and expanding peri-urban growth centers. Spatiotemporal scanning identified ten statistically significant clusters, characterized by an expansion toward expanding peri-urban growth centers, such as Licheng in Zengcheng, alongside a resurgence in traditional central urban areas like Meihuacun in Yuexiu, Baihedong in Liwan and their surrounding regions. This study reveals a significant spatial-temporal clustering of scarlet fever in Guangzhou from 2005 to 2024, characterized by an overall upward trend and a notable recent resurgence. The high-risk regions were predominantly localized within the central urban regions and expanding peri-urban growth centers, such as Helong, Licheng, Meihuacun, and their surrounding regions. The outbreak mostly affects kindergarten children aged 3-6 years and students aged 7-10 years, with winter and spring as peaks. Control strategies should target high-risk seasons, populations and regions to reduce scarlet fever cases.
Eye-color mutants provide easily distinguishable visual markers for genetic analysis and genome editing, yet the molecular basis of naturally occurring eye-color variation in Nilaparvata lugens remains unclear. Here, we combined classical genetic analysis, candidate-gene screening, and CRISPR/Cas9 genome editing to elucidate the genetic basis of a stably inherited orange-eye phenotype and evaluate the editing performance of different sgRNA strategies. The orange-eye phenotype was inherited as a single autosomal recessive trait, and the mutant strain showed only limited fitness differences from the WT strain. A 1287-bp insertion spanning exon 13 and the adjacent intronic region of Nlscarlet introduced a premature stop codon, truncating NlScarlet after the fifth transmembrane helix. The insertion completely cosegregated with the orange-eye phenotype, and CRISPR/Cas9-mediated disruption of Nlscarlet recapitulated the phenotype, demonstrating that this insertion underlies the natural mutation. A separate in-frame deletion of lysine 535 produced a dark-orange-eye phenotype, and structural modeling suggested that this residue may contribute to the interaction between the NlWhite/NlScarlet transporter complex and 3-hydroxykynurenine. Using Nlscarlet as a visually scorable marker, two multiple-sgRNA strategies, each using four sgRNAs, increased the proportions of G0 individuals with complete loss-of-function phenotypes from 30.97% to 84.73% and 92.47%, respectively, and of mutant-eyed G1 progeny from 37.33% to 81.33% and 90.67%, respectively. Heritable mutations generated by both strategies were predominantly large deletions. These findings identify the genetic basis of a natural orange-eye mutation in N. lugens and establish multiple-sgRNA editing as an efficient strategy for rapid functional screening in insects.
An increased incidence of group A Streptococcus-related scarlet fever has been observed in Shanghai since 2011, characterized by the co-circulation of both emm12 and emm1 strains. The comparative virulence potential of these two dominant strains, which is critical for understanding their dynamics and severity, remains largely under researched. This study aimed to systematically compare their virulence determinants to uncover the molecular basis for their successful dissemination. As the dominant strains that cause scarlet fever, 16 isolates each of both emm1 and emm12 were selected from the Children's Hospital at Fudan University between 2011 and 2022 using a stratified random sampling method. We compared the two strain types in terms of the positivity rate of virulence factors, adherence and internalization capacity into epithelial cells, biofilm formation capacity, and resistance to innate immune responses. Genomic analysis revealed significant divergence between the emm1 and emm12 strains, particularly within the fibronectin-collagen-T antigen (FCT) region and fibronectin-binding protein and superantigen genes. These genetic differences were reflected in functionally distinct phenotypes. Emm1 strains (linked to FCT2) exhibited a superior colonization capacity, demonstrating rates of epithelial cell adherence and internalization that were approximately two-folds higher, and significantly enhanced biofilm formation compared to emm12 strains (linked to FCT4; P < 0.05). Furthermore, emm1 strains showed significantly greater resistance to innate immune clearance, with higher survival rates in human whole blood, serum, and phagocytic cells (P < 0.001). The enhanced in vitro colonization and immune evasion fitness of emm1 strains are likely attributable to their distinct virulence gene repertoire and expression profile. These findings suggest that the co-dominance of emm1 and emm12 may be driven by divergent pathogenic strategies. The continuous investigation of shifts in the prevalence of emm types and associated virulence factors is essential for understanding their epidemiology and informing strategies for controlling scarlet fever.
The scarlet gene encodes an ATP-binding cassette transporter involved in eye pigmentation across various insect species. In this study, we functionally characterized the scarlet homolog (Gbst) in the cricket Gryllus bimaculatus, a hemimetabolous model organism. Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9-mediated knockout of Gbst generated a stable yellow-eyed mutant line (Gbst-/-) with changed pigmentation evident from embryogenesis through adulthood. Quantitative real-time PCR analysis showed that scarlet expression was extremely low in Gbst-/-, and the transcript levels of white and brown were also reduced. Histological sections of the compound eyes showed that both WT and Gbst-/- mutant possessed complete and well-defined ommatidial structures, indicating that the scarlet gene does not affect compound eye structure. In addition, reproduction tests showed that knockout of the Gbst gene did not affect egg production or embryonic viability. These findings demonstrate that Gbst is a key factor involved in eye pigmentation in G. bimaculatus, and has potential for application as a visual transgenic marker gene.
The replenishment of specialized cells depends on the activity of stem cells. Recent advances in stem cell research have shown that the germline stem cells (GSCs) in Drosophila melanogaster can increase their mitotic activity in response to mating. Here, we show that this ability to respond to mating is eliminated if the males are mutant for either of the ABC transporters, White (W), Brown (Bw) or Scarlet (St), which are known for their role in eye pigmentation and amine production. However, reducing the expression of w specifically from the germline cells also caused a failure to increase GSC mitotic activity upon mating, suggesting that w is required intrinsically in the stem cells. The w gene is a common genetic background for genetic experiments and frequently used as a control. Our findings underline the importance of careful experimental design and control choice.
Scarlet fever has seen a sharp increase in its reported incidence in China since 2011, and this study focuses on Shanghai as a representative setting to systematically investigate its transmission dynamics by analyzing age structure. It further identifies high-risk age groups and provides a theoretical foundation for prevention and non-pharmaceutical intervention strategies. We developed an SIR model that incorporates age structure and seasonality of transmission rate. In parameter estimation, the methodology of the partially observed Markov process framework is employed to derive results based on monthly data. The time-varying reproduction number R0(t) is derived monthly from the next-generation matrix. Age-specific forces of infection are estimated to identify high-risk groups and quantify how school-term-driven contact patterns modulate transmissibility. The force of infection peaked in children aged 7-9 years, whereas the force of infection was highest among adults aged 35-39 years. The seasonal amplitude for transmission among school-aged groups was 39% (95% CI: 37-41%). The estimated R0(t) varied seasonally between 3.02 and 8.83. The transmission rate in Shanghai shows strong age heterogeneity and school-driven seasonality. Children aged 7-9 years are the highest-risk group, and interventions should target them during periods of high R0(t).
Sterculia lanceolata, a tree species of the Malvaceae family with notable ornamental and medicinal value, has long been constrained in genetic research and breeding applications due to the lack of genomic resources. In this study, we report for the first time a high-quality, chromosome-level genome assembly of this species, aimed at elucidating its evolutionary history and the genetic basis of key traits. We constructed the genome using PacBio HiFi sequencing and further assembled it into 20 pseudochromosomes with the aid of Hi-C technology, yielding a final genome assembly size of 602.8 Mb with a contig N50 of 29.3 Mb and a BUSCO completeness of 98.7%. The assembly includes the identification of 20 pseudochromosomes and the annotation of 35,873 protein-coding genes, with an annotation rate of 96.4%. By integrating genomic data from other Malvaceae species, we analyzed the karyotype evolution of S. lanceolata and revealed the basal ploidy level of the family. Comparative genomic analyses uncovered significant syntenic relationships and whole-genome duplication (WGD) events among Malvaceae species, thereby clarifying the trajectory of karyotype evolution. Moreover, the study identified key regulatory gene families associated with fruit dehiscence (homologs of SHP1/2, FUL, IND, and ALC) that have undergone extensive expansion in S. lanceolata as a consequence of ancient polyploidy events. The reference genome provided in this study not only serves as a critical resource for evolutionary research in Malvaceae but also establishes a foundational framework for molecular breeding, genetic improvement, and conservation of S. lanceolata and related species.
Scarlet fever, known in Persian as "Tab-e Sorkh," is a bacterial infection caused by Streptococcus pyogenes. During the Qajar era (1796-1925), it was often deadly and reached pandemic levels in the 19th century. Both traditional Iranian and European medicine described its symptoms, but few comparative studies exist. By analyzing historical Persian texts, European medical reports, and modern literature, this study compares how the disease was understood and treated. Symptoms like rash and fever were widely recognized, and mortality was high before antibiotics. Traditional treatments followed humoral theory, including herbal remedies and bloodletting. Outbreaks peaked in cold months, mostly affecting children aged 5-15 years - a pattern seen in both medical systems. From the 1820s to 1880s, scarlet fever caused global outbreaks, especially in Iran. This research shows how combining historical perspectives can deepen our understanding of infectious diseases and their treatment across time.
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This study characterises the polyphenol profile (LC-MS), antiglycation (BSA-GLU, BSA-FRU, BSA-MGO), and antioxidant potential (ABTS, DPPH) of A. arguta ('Scarlet September Kiwi') and A. kolomikta ('Lande') fruit before and after extract purification. A total of 48 polyphenols belonging to 11 chemical groups were identified. Crude Scarlet extract showed higher TPI (1079.51 µg/g dw) than the crude Lande (761.13 µg/g dw), with quercetin glucoside accounting for 71% of TPI. Crude Lande extract was dominated by caffeic acid glucoside (39% TPI). Purification markedly increased TPI values to 4082.13 µg/g dw (Scarlet) and 2550.51 µg/g dw (Lande). The crude extracts more effectively inhibited glucose- and fructose-induced protein glycation (IC50 = 1.81-7.71 mg/mL) than methylglyoxal-mediated glycation (IC50 = 14.33-24.26). Purification significantly enhanced antiglycation efficacy in all models (IC50 = 0.47-1.78), as well as antioxidant capacity (IC50 = 0.10-0.67 mg/mL). Statistical analyses revealed a strong alignment between the glycation-inhibitory activity and the tested antioxidant potential. These findings suggest that targeted purification enhances the functional potential of Actinidia species, making them promising sources of bioactive compounds against oxidative stress and protein glycation-related disorders.
Cases of scarlet fever have increased since 2011 across China. However, genomic epidemiological knowledge of Streptococcus pyogenes, the causative agent, is limited. Here we present a longitudinal analysis of S. pyogenes isolates (n = 1,029) across emm1 and emm12 genotypes collected from eight provinces across China between 1993 and 2024. Genomic data integrated with national scarlet fever incidence data confirmed emm12 and emm1 as dominant genotypes underlying five incidence peaks and disease resurgence in 2024. Phylogenetic analysis showed independent evolution of these genotypes in China compared to global epidemic lineages. Four emm12 clades were present in China before 2011 but were replaced by a single clade, Clade II, by 2020. A dominant emm1 clade, M1china, distinct from global lineages and the M1UK lineage, represents >98% of emm1 cases in China. Sub-clade expansion coincides with carriage of integrative conjugative elements containing macrolide and tetracycline resistance genes and virulence gene-encoding prophage. Ongoing maintenance of these elements in emm1 and emm12 populations likely underlies the resurgence of scarlet fever in China.
This study compares sediment and pomace from juice production of three Elaeagnus multiflora cultivars (Jahidka, Marianna, Sweet Scarlet) as potential sources of bioactive compounds and minerals, with Marianna profiled for the first time. We quantified macro- and microelements (K up to 1670 mg/100 g d.m.), vitamin C (117-211 mg/1000 g), carotenoids (up to 1183 mg/100 g d.m.), chlorophylls, and tocopherols (α-tocopherol up to 35.59 mg/100 g d.m.). UPLC-PDA-MS/MS identified 15 polyphenols; totals reached 31.39-314.77 mg/100 g d.m. Pomace was richer in flavonoid glycosides and showed 30-38% higher ABTS/DPPH activity, whereas sediments concentrated lycopene, phytoene and α tocopherol and more strongly inhibited α-amylase and α-glucosidase (up to 1.5 fold); multivariate analyses separated samples by fraction and cultivar, with Sweet Scarlet pomace having a distinct pigment profile and Jahidka the greatest bioactive diversity, while cadmium was below the detection limit and the analysed toxic elements were low, although no comprehensive safety evaluation was performed.
DNA methylation changes are reliable biomarkers of aging, but the driving mechanisms remain poorly understood. Here we present SCARLET (Stem Cells and Age-ReLated Epigenetic Trajectories), a parsimonious mathematical model that describes how methylation changes in blood arise and propagate through hematopoietic stem cell divisions. Using a large human cohort, we demonstrate that seemingly distinct age-related methylation patterns can be explained by a unifying mechanistic model. We show that SCARLET captures known drivers of epigenetic aging, with accelerated individuals showing reduced ratios of stem cell pool size to division rate (N/s). Applying SCARLET to methylation data from 11 mammalian species reveals that N/s scales with maximum lifespan, suggesting that evolutionary adjustments to stem cell dynamics, rather than epigenetic maintenance efficiency, drive the previously observed relationship between methylation rates and lifespan. Our findings provide a quantitative framework for understanding epigenetic aging and suggest that stem cell dynamics may be a key driver of aging across mammals.
This study aimed to determine the most suitable sampling unit (apical, middle, or basal leaf strata) and sampling technique (direct counting or tray beating) for sap-sucking pest groups (aphids, thrips, lace bugs, and whiteflies) across different crops in an agroforestry system (AFS). The study was conducted with kale, okra, tomato, and scarlet eggplant over three cropping seasons (one in 2023 and two in 2024). The main pest species were Lipaphis erysimi on kale and Aphis gossypii on okra (aphids); Corythaica passiflorae on scarlet eggplant and Gargaphia lunulata on okra (lace bugs); Bemisia tabaci on kale and tomato (whiteflies); and Frankliniella schultzei on tomato and Thrips spp. on okra (thrips). A generalized linear mixed model (GLMM) with negative binomial distribution was used to evaluate the effects of sampling technique, sampling unit, and crop on pest density. Optimal sampling combinations were defined based on higher mean densities and lower coefficients of variation (CV). Direct counting was the most effective technique for aphids, whiteflies, and lace bugs, whereas tray beating was more efficient for thrips. However, the optimal sampling unit varied strongly according to crop-pest interactions. These results indicate that, although sampling techniques can be partially standardized by pest group, the selection of the sampling unit must consider crop-specific interactions. This approach improves sampling efficiency and supports decision-making in Integrated Pest Management programs in diversified agroecosystems such as AFS.
Predicting how the thermoacoustic response of a combustor changes across operating conditions is a long-standing challenge because small uncertainties in the flame response lead to large uncertainties in the thermoacoustic response. In this paper, we address this challenge for the Rolls-Royce SCARLET test rig using a combination of Bayesian inference, Gaussian process regression, and information-theoretic experiment design. Starting from a physics-based acoustic network model whose flame parameters are inferred at several operating conditions using Bayesian inference (described in a companion paper), we use Gaussian process regression in Part A to learn how the five parameters of a flame model vary with six operating condition parameters. The resulting Gaussian process model predicts the flame response at unseen conditions with quantified uncertainty, and, when coupled into the acoustic network, produces operating maps of the full thermoacoustic response. In Part B, we use metrics from information theory to identify the small number of forcing frequencies that are most informative about the flame parameters. For the SCARLET rig, three optimally chosen frequencies recover the flame transfer function to the same fidelity as the full dataset of around 20 frequencies forced from both upstream and downstream, reducing the data required by up to 90%.
Early embryogenesis and their underlying regulatory mechanisms in crustaceans remains unclear at the cellular level. Here, we mapped the early developmental stages of marine shrimp Palaemon carinicauda using single nucleus RNA sequencing (snRNA-seq), spanning the transitional stages of blastula to protozoea. Profiling over 60,000 nuclei, we identify six distinct embryonic cell types, including the multiple neuronal subtypes, extracellular matrix- producing cells, cuticle-forming cells, and an eye-related cells that emerged during protozoea development. Cell-type identities were validated using selected marker genes expression and spatial expression patterns via fluorescent in situ hybridization (FISH). PcWhite and PcScarlet contain a highly conserved nucleotide-binding domain (NBD) motif, including Walker A, ABC signature sequence and Walker B domain and a conserved six transmembrane domain (TMD). RNA interference (RNAi) analysis targeting the ABC transporter genes White (W) and Scarlet (St) demonstrated that these genes are essential for eye pigment precursor transport, morphogenesis, and embryonic viability. Collectively, this integrative approach demonstrates the robustness of snRNA-seq for dissecting early embryogenesis in non-model species, linking cell-type-specific gene expression to key developmental processes that enables comparative evolutionary genomics across crustaceans.