Cryptic differentiation poses a significant challenge to taxonomy, particularly in morphologically conserved lineages whose divergence is not immediately apparent. In eusocial insects like ants, where species boundaries are often maintained through chemical rather than morphological differentiation, integrative methodologies are essential for resolving taxonomic complexity. Here, we present compelling evidence for the recent divergence of African carpenter ants initially identified as Camponotus maculatus into two distinct sub-populations. This divergence is supported through an integrative approach combining chemical, behavioral, and genetic analyses. Most strikingly, we identify two sharply contrasting chemotypes characterized by categorically different cuticular hydrocarbon (CHC) profiles that unambiguously separate the investigated ant populations. Concordantly, behavioral assays reveal that worker ants consistently exhibit aggression toward individuals with opposing chemotypes, while displaying affiliative behaviors toward shared chemotypes irrespective of colony affiliation. Genetic barcoding further corroborates these findings, indicated by phylogenetic clusters largely corresponding with the two chemotypes. Our results highlight the primary role of chemical differentiation within morphologically indistinguishable populations to resolve cryptic sub-population structures. These findings also provide valuable insights into potential early-stage chemical differentiation mechanisms in eusocial insect populations.
Impaired ventricular-arterial coupling (VAC) is associated with adverse health outcomes. However, the predictive values of VAC calculated by different non-invasive methods remain uncertain. We aimed to assess prognostic values of VAC calculated as the ratio between arterial elastance (Ea) and left ventricular end-systolic elastance (Ees) and between carotid-femoral pulse wave velocity (PWV) and global longitudinal strain (GLS). In 3634 Atherosclerosis Risk In Communities study participants (57.4% women; mean age, 75.1 years), Cox proportional hazard models were constructed to determine associations of VAC metrics with heart failure (HF) and all-cause mortality. Risk prediction models were employed to examine prediction improvement of VAC beyond established risk factors. Over approximately 6.3 years (median), 316 participants experienced HF, and 482 died. The hazard ratios of HF related to 1-SD increment in VAC metrics were 1.28 (95% CI, 1.18-1.38; P < 0.001) for Ea/Ees and 1.40 (1.27-1.54; P < 0.001) for PWV/GLS with adjustments applied for potential confounders. PWV/GLS was the only VAC parameter associated with mortality (adjusted HR, 1.18; 1.08-1.28; P < 0.001). PWV/GLS was observed to have stronger associations with all outcomes in individuals aged ≤74 years than those aged >74 years (P for interaction ≤0.034). The addition of VAC maker to the conventional risk factors improved risk prediction for incident HF (P ≤ 0.010) assessed by C statistics, net reclassification improvement, and integrated discrimination improvement for Ea/Ees (0.702, 22.4%, and 1.40%) and for PWV/GLS (0.701, 22.1%, and 1.46%). In the general population, impaired VAC was associated with a higher risk of incident HF and total mortality.
Activities of daily living (ADL) are associated with declines in physical fitness and subjective health. However, it remains unclear as to whether ADL impairments are related to specific components of physical fitness and health variables. Therefore, we examined differences between community-dwelling older persons with versus without ADL impairments with regard to various physical fitness components, physical complaints as well as subjective and objective health outcomes. Cross-sectional study among 254 participants aged ≥ 55 years [51% female; 84 with ADL impairments; mean (SD) age 62.1 (6.6) years] enrolled in the population-based "Gesundheit zum Mitmachen" study in Southwestern Germany. ADL, physical complaints and subjective health status were assessed using a self-report questionnaire, physical fitness (cardiorespiratory fitness, strength, gross motor coordination, flexibility, and functional mobility) was assessed using a fitness test battery, and objective health status was derived from health exam performed by a physician. We ran analyses of covariance, adjusted for age, sex, body mass index and education. Participants with ADL impairments had statistically significantly worse subjective (p < 0.001) and objective (p < 0.001) health and reported more physical complaints (p < 0.001) compared to those without ADL impairments. Regarding physical fitness, ADL-impaired participants performed worse in 10 out of 12 variables. The findings provide additional evidence that ADL impairments are related to decreased objective and subjective health and physical fitness in older community-dwelling adults. Future studies employing more comprehensive, preferably objective, ADL assessments and considering cognitive impairments, which may also impact ADL performance, are warranted.
We previously established an interpretable combinatorial data-mining framework to identify combinations of clinical factors predictive of heart failure. Because hypertension (HT) is a major contributor to heart failure, accurate prediction of new-onset HT is critically important for prevention. To identify combinations of clinical factors predictive of HT onset using a novel limitless-arity multiple-testing procedure (LAMP) and to estimate the probability of developing HT. We analyzed 2,610,286 individuals without HT who underwent annual health check-ups starting in 2005-2015 and were followed for 5 consecutive years without missing data. Using the LAMP method, we systematically identified statistically significant combinations of fewer than four clinical factors associated with HT onset. Among 28,618 subjects used for rule discovery, 4802 combinations predictive of HT onset were identified. The remaining 2,581,668 individuals were classified into one group with no predictive combinations (G0) and 20 groups (G1-G20) according to increasing numbers of predictive combinations. The incidence of HT increased stepwise with the number of predictive combinations, as confirmed by Kaplan-Meier analyses (p < 0.001). Receiver-operating characteristic analysis demonstrated a moderate discriminative performance (area under the curve = 0.69). We identified combinations of routine clinical parameters that predict new-onset HT in the general population. A greater number of matching predictive combinations was associated with a proportionally higher probability of developing HT. This interpretable combinatorial data-mining framework may enable risk stratification for HT and support early preventive strategies.
The epithelial ovarian cancer (EOC) with normal CA125 level is relatively rare. This study aims to develop a nomogram model for predicting the overall survival (OS) of EOC patients with normal CA125 level. A total of 13,068 patients with epithelial ovarian cancer (EOC) were extracted from the SEER database, and an additional 138 patients were recruited from our hospital as an external validation cohort. We found that the OEC patients with normal CA125 levels tend to have a better prognosis than those with elevated CA125 levels. Multivariate Cox regression analysis showed that age, summary stage, histology, and lymphadenectomy status were important factors affecting the prognosis of EOC patients with normal CA125 level.
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This study aimed to investigate the insertional patterns of the Achilles tendon at the calcaneus in Korean cadaveric lower limbs and to evaluate whether morphometric characteristics differ according to insertional pattern. Fifty-five Korean cadavers (110 lower limbs) were dissected. Nine lower limbs with severe deformities were excluded, and 101 lower limbs were included in the final analysis. After separation of the tendon components of the triceps surae, insertional patterns were classified according to the criteria proposed by Edama et al. Tendon length, width, and thickness were measured at predefined reference points. Three insertional patterns were identified. Type 2 was the most common pattern (55.4%), followed by Type 1 (22.8%) and Type 3 (21.8%). Tendon width and thickness differed significantly according to measurement level (p < 0.001), with the greatest values observed at the calcaneal insertion. However, no significant differences in tendon length, width, or thickness were identified according to insertional pattern. Type 2 was the predominant insertional pattern of the Achilles tendon in Korean cadaveric lower limbs. Although morphometric characteristics varied along the course of the tendon, they were not significantly associated with insertional patterns. These findings provide baseline anatomical data regarding insertional variation and morphometric characteristics of the Achilles tendon.
Describe rates of intraventricular hemorrhage (IVH) in the VentFirst cohort, model risks for severe IVH and compare IVH rates to a contemporaneous population. Sub-analysis of the VentFirst multi-center randomized trial. Head ultrasound findings from 548 infants <29 weeks' gestation who survived to first head ultrasound study in the VentFirst trial were analyzed. Any grade of IVH was found in 31% and severe (grade III/ IV) IVH in 8%. Logistic regression indicated gestational age (GA), twin gestation and 1-minute Apgar as risks for severe IVH. Odds of any IVH and severe IVH were lower in the VentFirst population than in a comparable population in the Vermont Oxford Network. Severe IVH in the VentFirst trial was associated with low GA, twin gestation and low 1-minute Apgar score. The lower odds of IVH for the study cohort compared to a similar population may reflect optimized delivery conditions. ClinicalTrials.gov Identifier: NCT02742454.
Obeticholic acid (OCA), a synthetic analog of chenodeoxycholic acid, was approved in 2016 for the treatment of primary biliary cholangitis. Early clinical trials revealed elevated liver biomarkers in healthy subjects receiving supratherapeutic OCA doses (100-250 mg). OCA was also evaluated as a treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) but was not approved by the FDA due to liver safety concerns. In this in silico study, we investigated mechanisms of OCA-associated liver injury in virtual healthy and MASLD populations receiving supratherapeutic and therapeutic (10-25 mg) doses, respectively. OCA and metabolite exposures in plasma, sinusoidal blood, liver, and gut compartments were simulated using a physiologically based pharmacokinetic model. In the virtual MASLD population, exposures were increased 2-, 5-, and 10-fold in plasma, sinusoidal, and/or liver compartments relative to baseline. Mechanistic parameters relevant to OCA-mediated liver injury, including bile acid transporter inhibition and mitochondrial dysfunction, were incorporated into the DILIsym model. Predicted liver injury was reported as evaluation of drug-induced serious hepatotoxicity (eDISH) plots, and elevations in alanine aminotransferase, aspartate aminotransferase, and total hepatic bile acids. DILIsym simulations recapitulated liver biomarker elevations observed at supratherapeutic OCA doses in healthy subjects and predicted biomarker increases in the MASLD population under conditions of 5- and 10-fold increased exposures relevant to this population. Bile acid transporter inhibition alone reproduced simulated biomarker elevations, whereas mitochondrial uncoupling alone predicted increased biomarkers only at the highest exposures. Results suggest that DILIsym modeling would have predicted the liver safety concerns that led to withdrawal of OCA from the US market.
Shortly after its first outbreak in Wuhan, the SARS CoV-2 spread worldwide. This study determined SARS CoV-2 seroprevalence and compared anti-RBD IgG titre distributions among seropositive samples across four repeated cross-sectional surveys conducted during successive epidemic waves from August 2020 to January 2022. Age-specific seroprevalence and titre patterns were also examined across children, adolescents, and adults. We conducted a seroepidemiological cross-sectional study over four epidemic waves periods. A stratified 1,096 samples, reflecting the age and sex distribution of the Accra population, was selected from 15,000 residual clinical samples. Adjusted seroprevalence increased from 58.3% (95% CI: 53.9-62.6%) in wave 1 to > 90% by wave 2 and remained ≥ 96% in waves 3 and 4. Adults aged ≥ 20 years reached near-universal seropositivity earlier than children, who accumulated exposure more gradually. Despite this early plateau, geometric mean anti-RBD IgG concentrations increased from 162 BAU/mL in wave 1 to 625 BAU/mL in wave 3, stabilising at 584 BAU/mL in wave 4. Analyses of antibody titre distributions demonstrated that progressively larger proportions of adults showed concentrations substantially exceeding wave 1 baseline levels in later waves, indicating age-related differences in cumulative antigenic exposure. Across successive epidemic waves, Accra experienced intense and repeated SARS CoV-2 transmission, resulting in near-universal exposure of the adult population by May 2021. Children and adolescents showed a slower and more gradual increase in both seroprevalence and antibody concentrations. Anti-RBD IgG titres increased across successive waves and stabilised after August-November 2021, consistent with sustained cumulative antigenic exposure at the population level.
Aims To assess whether area-level deprivation predicts the population-adjusted distribution of National Health Service (NHS) dental practices within a socioeconomically diverse English local authority.Methods Analysis of dental practice density (dental practices per 10,000 residents) across the Index of Multiple Deprivation (IMD) deciles. Decile 1 represents the most deprived areas and decile 10 the least deprived.Results A non-linear relationship was observed between deprivation and dental practice density. Deprivation did not predict dental practice distribution, with upper-middle deciles showing the highest provision. The least deprived decile (10) had the lowest NHS dental practice density (0.36 per 10,000 residents). The most deprived areas (deciles 1-3) showed variable practice densities (0.52, 0.93, 0.53).Conclusions NHS dental practice density varied non-linearly across deprivation deciles, with no statistically significant association between deprivation and practice density after population adjustment. These findings indicate that deprivation alone does not explain the spatial distribution of NHS dental practices. Commissioning strategies must incorporate data on these factors, rather than relying on deprivation indices. Areas with large populations, but little NHS dental provision, may require distinct policy responses.
Depression and anxiety are common mental disorders with substantial public health burden, yet the relative contributions of potentially modifiable physiological, psychosocial, and female-specific reproductive factors to their development remain incompletely understood, particularly across sex and age groups. We aimed to examine the associations of these factors with incident depression and anxiety in women and men and to estimate their population attributable fractions (PAFs). This prospective cohort study included 87,648 participants from the UK Biobank (44,383 women and 43,265 men) recruited between 2006 and 2010 and followed for a median of 13.7 years. Incident depression and anxiety were defined as the first recorded ICD-10 diagnosis or new-onset symptom positivity during follow-up among participants free of the respective condition at baseline. Sex-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and individual and combined PAFs were calculated separately in women and men. During follow-up, 5.65% of women and 4.21% of men developed depression, while 6.02% and 3.60% developed anxiety, respectively. Psychosocial factors contributed the largest population burden in both sexes. Neuroticism symptoms had the largest PAFs for depression (women: HR 2.61, 95% CI: 2.36, 2.88; PAF 48.61%, 95% CI: 44.71%, 52.68%; men: HR 3.50, 95% CI: 3.07, 3.98; PAF 59.93%, 95% CI: 55.41%, 64.13%) and anxiety (women: HR 2.82, 95% CI: 2.56, 3.11; PAF 51.75%, 95% CI: 47.93%, 55.68%; men: HR 2.94, 95% CI: 2.58, 3.36; PAF 53.80%, 95% CI: 48.89%, 58.62%). The additive combined PAF of psychosocial factors was 61.17% in women and 66.90% in men for depression, and 59.98% and 56.80% for anxiety. Among physiological factors, obesity contributed the largest PAF for depression in both sexes, while chronic inflammation was associated with both outcomes in both sexes. In women, reproductive factors provided additional contributions, with hormone replacement therapy showing the largest PAFs for depression (HR 1.48, 95% CI: 1.34, 1.62; PAF 13.43%, 95% CI: 10.15%, 16.84%) and anxiety (HR 1.32, 95% CI: 1.20, 1.44; PAF 9.43%, 95% CI: 6.38%, 12.80%). Age-stratified analyses showed that psychosocial contributions remained substantial across age groups, whereas physiological and reproductive contributions were more pronounced in later life. When all factors were considered jointly, the overall additive combined PAFs were 67.54% in women and 69.71% in men for depression, and 61.23% and 57.82% for anxiety. These findings support sex-informed and life course-oriented prevention strategies for depression and anxiety.
Orofacial clefts impose a substantial burden on low- and middle-income countries (LMICs), yet evidence on preventable environmental determinants, including agrochemicals, remains sparse. To quantify the association between maternal agrochemical exposure during pregnancy and nonsyndromic orofacial clefts (NSOFCs) across eight LMICs. This population-sampled, unmatched case-control study included questionnaires administered to mothers of children with NSOFCs (cases) and mothers of unaffected children (controls) in the Democratic Republic of Congo (DRC), Guatemala, Honduras, Madagascar, Morocco, Nicaragua, the Philippines, and Vietnam. Binary logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported agrochemical exposure. Sub-analyses examined cleft subtypes and country-specific effects. 3791 cases and 3190 controls recruited from 2012 to 2020 were included for the descriptive statistics. Agrochemical exposure was uncommon (5.4% of cases; 1.3% of controls), and DRC, Guatemala, Morocco, and Nicaragua were excluded from the binary logistic regression due to insufficient exposure reports. After adjustment, any pregnancy exposure was associated with an increased odds of NSOFC (OR 2.34, 95% CI 1.47-3.71); a comparable estimate was observed for first-trimester exposure (OR 2.63, 95% CI 1.37-5.04). The odds ratio was elevated for cleft lip ± cleft palate (OR 2.35, 1.45-3.81), with an elevated but non-significant point estimate for isolated cleft palate (OR 1.52; 95% CI: 0.73-3.15). Country-stratified models identified significantly elevated associations in Vietnam (OR 3.91, 1.35-11.30) and Honduras (OR 4.65, 1.81-11.91). Maternal agrochemical exposure during pregnancy was linked to NSOFC in the largest multicountry study in LMICs to date examining this exposure. Identifying environmental risk factors specific to agricultural communities in LMICs is crucial for informing effective public health interventions, ultimately reducing the burden of orofacial clefts among underserved populations. This study of nearly 7000 participants across eight low- and middle-income countries found that maternal agrochemical exposure during pregnancy was associated with increased odds of nonsyndromic orofacial clefts in children. Elevated estimates observed in Vietnam and Honduras highlight the importance of understanding environmental determinants of cleft risk in specific agricultural contexts and informing targeted prevention strategies in agricultural communities.
Linear transport infrastructure fragments habitats, but its edges can serve as significant refuges for invertebrates. Management of these verges is crucial to realise this conservation potential, but the impact of specific habitat measures on epigeic arthropods remains poorly understood. This study assessed the impact of roadside habitat management on the diversity and composition of epigeic arthropods, using ground beetles (Carabidae) and harvestmen (Opiliones) as bioindicators at the Nitra-Selenec expressway junction, Slovakia. Over two years, we used pitfall traps to sample epigeic arthropods at ten sites managed under three different regimes: passive management (no intervention), active management with renewal/seeding (commercial grass-herb mixture), and active management with mulching only. We analysed the influence of management, vegetation structure, and landscape variables on species assemblages using redundancy analysis and predicted population trends using machine learning. We recorded 1,416 carabids (50 species) and 1,409 harvestmen (6 species). The renewal/seeding intervention had a significant negative effect on the community composition. The structure of the vegetation, specifically the cover of the herb layer and species richness of the shrub layer, were the most significant positive drivers of community assembly. Furthermore, distance from the road significantly influenced species distribution. Analysis of population trends revealed a gradual increase in carabid abundance over time, but an alarming decline in harvestmen. Active revegetation with commercial seed mixtures creates a homogeneous habitat that is less suitable for diverse epigeic communities than passive management. The structural complexity provided by various native vegetation is a key factor in supporting invertebrates. Implications for insect conservation: We recommend that roadside managers prioritise passive management or regionally appropriate native seed mixtures over commercial revegetation, maintain structural complexity of vegetation through a reduced frequency of mowing (1-2 times annually at ≥ 10 cm height), and adopt mosaic approaches that combine intensive mowing only in safety-critical zones with extensive management elsewhere.
Steroid-resistant (SR) graft-versus-host disease (GvHD) remains a severe complication following allogeneic hematopoietic progenitor cell transplantation (HPCT). Mesenchymal stromal cell (MSC)-based therapies hold promise but face challenges in demonstrating clinical efficacy. This study investigates how in vitro immunopotency, a critical quality attribute (CQA) of MSC, correlates with patient outcomes to inform MSC-based therapy development for SR-GvHD. In this retrospective descriptive case series study, we evaluated 49 patients (median age: 10 years, interquartile range, IQR: 5-17; 19 females, 30 males) treated for post-allogeneic HPCT acute (N = 40) and chronic (N = 9) SR-GvHD across 4 tertiary hospitals (2018-2022). Clinical-grade MSCs derived from the Wharton's jelly (MSC, WJ) of the umbilical cord of unrelated donors were administered compassionately at a target dose of 1 × 10⁶ MSC, WJ/kg for a median of 4 infusions at days 1, 4 and once weekly thereafter (197 total infusions). MSC were stratified by immunopotency (in vitro suppression of mixed-lymphocyte reactions: >70% vs. 30%-70%) using a validated assay. An overall response was achieved in 71.4% of patients at day 28 post-treatment (complete response in 11 patients), with 1-year survival of 55.1%. Overall survival in acute GvHD responders was significantly different (P = 0.012) than in the non-responding population. This was especially relevant in acute GvHD patients with improved overall survival in the population under 12 years (P = 0.039). Remarkably, higher in vitro immunopotency strength of MSC, WJ batches correlated with improved clinical responses in patients under 12 years (N = 28, P = 0.039). MSC, WJ therapy proved safe and effective for patients with SR-GvHD, with clinical response rates correlating significantly with measured immunopotency levels. These findings highlight the importance of defining meaningful CQAs and validated release criteria to ensure the therapeutic consistency of MSC-based products.
Large carnivore populations face numerous threats, yet leopards (Panthera pardus) remain understudied in Bhutan, where conservation is primarily focused on tigers (Panthera tigris). We evaluated the bottom-up and top-down influences on leopard habitat use, vital rates, and activity patterns, and provide the first nationwide estimate of leopard density in Bhutan. Using nationwide camera trap surveys from 2014-2015 to 2021-2022, we applied spatially explicit capture-recapture (SECR) models to estimate leopard density, dynamic two-species occupancy models to assess leopard-tiger habitat use, colonization, and local extinction, and activity-overlap analyses to evaluate temporal partitioning. Mean leopard density was 1.02 individuals/100 km2 (95% CI 0.89 -1.16), yielding a national population of 318.73 ± 21.73 SE individuals. Leopard density declined with elevation, stream density, and tree cover, while tiger density, human settlement density, and prey availability had weaker context dependent effects. Estimated site use was higher for leopards than tigers and declined with elevation and stream density for both species, while local extinction declined with increasing prey density. Leopards and tigers showed high diel overlap, suggesting little temporal avoidance. Together, these results suggest that leopard persistence in Bhutan's montane landscapes is structured more strongly by bottom-up habitat and prey conditions than by tiger suppression.
Leishmaniasis remains a major public health challenge in many tropical and subtropical regions despite long-standing emphasis on controlling adult sandflies. This commentary highlights an important ecological gap that has received limited attention: the immature stages of sandflies. Unlike mosquitoes, sandflies develop in cryptic terrestrial microhabitats that are rarely detected through routine surveillance. Consequently, most vector control programmes concentrate on suppressing adult populations, while the biological processes that generate new adult vectors remain poorly understood. Recent ecological studies indicate that breeding activity may be spatially structured and biologically detectable. Surveillance approaches that consider oviposition behaviour and breeding ecology may therefore help make vector population dynamics more measurable and support more sustainable, biology-based control strategies.
The COVID-19 pandemic prompted extraordinary response measures in Central Asia (Kazakhstan, Kyrgyzstan, and Mongolia), but mortality outcomes varied. This retrospective population-based ecological study assessed age-standardized COVID-19 mortality rates (ASMRs per 100,000) from January 2020 to December 2021. Monthly COVID-19 deaths and population data by age and sex were obtained from official statistical and health sources. ASMRs were calculated using direct age standardization; monthly trends were examined by country, sex, and age group using joinpoint regression and interpreted in relation to governmental mitigation measures and circulating SARS-CoV-2 variants. Rates were higher in men than in women: in Kazakhstan, 24.8 vs. 12.8 in 2020 and 87.3 vs. 67.6 in 2021, in Kyrgyzstan, 46.6 vs. 25.2 and 40.8 vs. 29.7, respectively; and in Mongolia, 91.5 vs. 73.1 in 2021, with no deaths reported in 2020. In 2021, the gap between men and women narrowed as female ASMR increased fivefold. COVID-19 mortality was observed among infants in Kazakhstan and children ages 0-4 in Mongolia (2021). Rates rose sharply from age 60, especially among men and showed distinct country-specific timing: an early peak in Kyrgyzstan, delayed acceleration in Kazakhstan, and a late rise in Mongolia. These results underscore the need for timely, coordinated, age- and sex-sensitive response measures and targeted protection of vulnerable groups.
Plant-parasitic nematodes, especially root-knot nematodes (RKNs) of the genus Meloidogyne, are major agricultural pests, causing crop yield losses of up to 80% in vegetables. Rapid reproduction intensifies soil infestation, and reliance on synthetic nematicides is declining due to environmental and health risks, necessitating sustainable alternatives. This study investigates the nematicidal potential of Carissa carandas L. methanolic seed extract, known for bioactive compounds, against Meloidogyne incognita juveniles (J2) and egg masses. In vitro assays at concentrations of 250, 500, and 1000 ppm demonstrated that the extract significantly increased J2 mortality and inhibited egg hatching in a concentration- and time-dependent manner. At 1000 ppm, the extract caused pronounced nematode anatomical disruptions, with Scanning Electron Microscopy (SEM) revealing severe structural changes in egg masses. An in-vivo pot experiment assessed C. carandas seed powder against M. incognita on muskmelon cv. 'Arkasiri' in a glasshouse setting, comparing its efficacy with Fluopyram, a commercial nematicide. Both treatments, applied 15- and 30-days post-inoculation, markedly improved plant growth parameters and reduced nematode indicators such as root galls and soil nematode populations. At 30 days, C. carandas treatment achieved a 94.26% reduction in root galls, while Fluopyram achieved 96.78%, with the latter showing a 99.10% decrease in nematode populations. GC-MS analysis of the extract identified bioactive compounds, including fatty acids, likely responsible for nematicidal effects. These results indicate that C. carandas seed extract offers a promising, eco-friendly approach for managing M. incognita, supporting plant-based nematicidal development for integrated pest management.
Vitiligo is a chronic autoimmune depigmenting disorder affecting 0.5%-2% of the global population, characterized by bidirectional interplay between psychological stress and disease progression, with accumulating evidence highlighting the central role and translational relevance of the neuro-endocrine-immune-cutaneous axis in its pathogenesis. Epidemiological data indicate over half of patients experience significant psychological stress prior to disease onset, while visible depigmentation markedly elevates the burden of depression and anxiety, establishing a self-amplifying pathogenic loop. Mechanistically, neural crest-derived melanocytes form functional "neuro-pigment units" with intraepidermal nerve endings, enabling bidirectional communication via neuropeptides including calcitonin gene-related peptide (CGRP) and substance P. Dynamic crosstalk among keratinocytes, sensory neurons, and melanocytes integrates neurotrophic and inflammatory signals to tightly regulate melanocyte survival and biological function. Sympathetic activation drives melanocyte injury via norepinephrine-mediated β2-adrenergic receptor signaling, while dopamine metabolites exacerbate apoptosis via the oxidative stress-Akt-Bad axis; context-dependent hypothalamic-pituitary-adrenal axis effects and light-melatonin-circadian clock disruption further promote immune dysregulation and melanocyte loss. Notably, neuromodulatory approaches like transcutaneous auricular vagus nerve stimulation show therapeutic promise by attenuating oxidative stress and limiting pathogenic CD8⁺ T-cell infiltration. These insights have fostered targeted strategies including CGRP receptor antagonists and dual antioxidant-neuroprotective natural compounds. Integrating neuroimmunological modulation with psychological and circadian interventions represents a promising precision medicine framework for vitiligo management.