Background/Objectives: Intra-articular polynucleotide (PN) has emerged as an alternative to hyaluronic acid (HA) for treating knee osteoarthritis (OA), with randomized controlled trials (RCTs) reporting similar or greater pain reduction. Real-world evidence on both single- and repeated-cycle outcomes remains limited. This study evaluated PN’s real-world effectiveness and safety and whether its pain reduction falls within ranges reported in previous PN–HA RCTs, and evaluated repeated-cycle outcomes. Methods: Clinical data from 1048 PN-treated OA patients were retrospectively reviewed. The safety set comprised 1024 patients with follow-up visits. The efficacy set included 975 patients who completed 3–5 weekly PN injections with evaluable VAS, CGI, and PGI data at baseline, 3, and 6 months. A repeated-treatment subgroup (n = 45) received a second PN cycle 6 months later. First-cycle outcomes were compared with PN–HA RCTs. Results: In the first-cycle (n = 975), VAS decreased from 50.30 mm to 23.02 and 22.43 mm at 3 and 6 months (−27.28 and −27.87 mm; p < 0.0001), showing a comparable magnitude to RCT-reported ranges (~27–41 mm). CGI improvement was 81.0% and 79.6%, and PGI improvement 78.8% and 78.1% at 3 and 6 months. In the repeated-treatment subgroup (n = 45), despite a lower second-cycle baseline VAS of 31.00 mm (vs. 50.30 mm at first-cycle baseline), VAS decreased to 14.07 mm and 17.33 mm at 3 and 6 months (−16.93 and −13.67 mm; p < 0.001), achieving comparable absolute post-treatment pain levels. Among 1024 patients, three mild-to-moderate arthralgia events (0.29%) occurred, with no serious device-related adverse events in either cycle. Conclusions: PN provided meaningful 6-month pain reduction in a comparable magnitude to previous RCTs and showed consistent benefit with repeated administration without new safety concerns.

Aging is accompanied by a chronic, low-grade inflammatory state known as "inflammaging," largely driven by dysregulated signaling of pro-inflammatory cytokines like IL-1 and TNF-α. The biological impact of these cytokines is modulated by the expression of their cellular receptors, which is influenced by genetic polymorphisms. However, the interplay between age, genetic variation, and cell-type-specific receptor expression remains incompletely characterized. This study aimed to determine the relative and absolute expression levels of IL-1 and TNF receptors on major immunocompetent cell populations in healthy donors of different age groups and to assess the influence of receptor gene polymorphisms on this expression. A cohort of 144 healthy donors was stratified into two age clusters using unsupervised clustering: a "young" group (18-31 years, n = 71) and an "older" group (32-59 years, n = 73). Membrane expression of TNFR1, TNFR2, IL-1R1, and IL-1R2 on T-lymphocytes, B-lymphocytes, and monocytes was analyzed by flow cytometry. The analysis included both the percentage of receptor-positive cells and the number of receptors per cell using absolute quantification with calibration beads. Genotyping for eight SNPs in the TNF1, TNFR2, IL1R1, and IL1R2 genes was performed via PCR-RFLP. The most pronounced age-related differences were observed in monocytes, in which the young cohort exhibited a significantly higher percentage of TNFR1- and TNFR2-positive monocytes, as well as a higher number of IL-1R1 receptors. In contrast, T-lymphocytes from the older cluster showed a higher percentage of TNFR2-positive cells. Genetic polymorphisms significantly modulated receptor expression in an age-dependent manner. For example, in the young cluster, polymorphisms primarily affected receptor levels on B-lymphocytes, whereas in the older cluster, the most significant associations were observed in monocytes. This study reveals significant, cell-specific alterations in the IL-1 and TNF receptor landscapes with age, with monocytes being particularly affected. The observed receptor downregulation in older adults is likely to reflect an active process of ligand-induced desensitization driven by chronic inflammation. Furthermore, genetic polymorphisms exert age-dependent effects on receptor expression, highlighting the dynamic interplay between genetics and immunosenescence. These findings provide a foundation for personalized strategies to mitigate inflammaging.

HighlightsWhat are the main findings?Integrating short isometric exercise bouts into regular physical education did not improve health-related functional or cardiovascular outcomes beyond standard PE alone.Improvements in muscular strength and functional capacity were observed over time in both groups, indicating a beneficial effect of regular physical education itself.Biological maturation influenced absolute strength levels but did not modify responsiveness to the isometric exercise intervention.What is the implication of the main finding?Adding brief isometric exercise to school-based physical education may not provide additional health benefits when regular PE already ensures sufficient physical stimulus.Well-designed standard PE programs may be sufficient to support health-related functional development in adolescents.Objectives: This study examined whether integrating an isometric exercise program into physical education (PE) lessons influences functional outcomes and cardiovascular risk markers in adolescents beyond the effects of standard PE alone. Methods: Boys aged 14–15 years were randomly assigned to an experimental group (EG, n = 19) or a control group (CG, n = 21). The EG completed a 6-week isometric exercise program integrated into PE lessons, while the CG followed the regular PE curriculum only. The intervention was based on hold isometric muscle actions (HIMA) with progressively increased volume. Anthropometric measures included body height, body mass, and body mass index (BMI). Body composition was assessed using bioelectrical impedance analysis. Functional capacity was evaluated using field-based measures of lower-limb strength and power (isometric mid-thigh pull, standing broad jump, squat jump, and countermovement jump). Systolic and diastolic blood pressure were measured as indicators of cardiovascular health. Results: A mixed model ANOVA showed that no significant group × time interactions were observed for body composition, functional outcomes, or blood pressure (all p > 0.05). Lean body mass increased over time in both groups (p < 0.01). Improvements in isometric mid-thigh pull (p < 0.01) and standing broad jump (p = 0.01) occurred irrespective of group allocation. Blood pressure remained unchanged. Linear regression revealed that biological maturation did not moderate intervention effects; however, more mature participants demonstrated higher absolute strength levels independent of the intervention (p < 0.05). Conclusions: The inclusion of an isometric exercise program within PE lessons did not provide additional benefits for health-related functional outcomes beyond standard PE alone. In its current format, isometric exercise does not appear to add sufficient value to justify its implementation as a stand-alone strategy in school-based PE.

BackgroundBlood biomarker studies most often use plasma samples. Suitability of serum as an alternative sample type remains unclear, despite many clinical chemistry laboratories preferring it over plasma. We compared the technical performance of the novel NUcleic acid‐Linked Immuno‐Sandwich Assay (NULISA), a blood‐based targeted proteomic biomarker assay, in plasma and serum samples processed from identical blood draws in a memory clinical cohort.MethodsPaired plasma and serum samples from 43 donors (75.2±7.8 years, 41.9% female, 32.6% probable AD) from the University of Pittsburgh ADRC were analyzed using the NULISAseq CNS disease panel 120 (v2) on an Alamar ARGOTM system, following manufacturer protocols. Protein levels were quantified by next generation sequencing, normalized, scaled, and log 2‐transformed to NULISA Protein Quantification (NPQ) units. Spearman's rank correlation assessed concordance between plasma and serum NPQs, while the Wilcoxon rank‐sum test evaluated differences in protein levels. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to determine diagnostic accuracy.ResultsThe assay achieved high analyte detectability (95.7% ± 14.2%) with low variability (%CV: 4.9%). Strong correlations (Spearman rho: 0.75‐0.96) were observed for traditional AD biomarkers (Aβ42, p‐Tau217, p‐Tau231, p‐Tau181, GFAP, NEFL) across both matrices. ANXA5, NRGN, and Oligo‐SNCA were the top three targets significantly more detectable in plasma (log2 plasma vs. serum fold change: 9.72, 9.48, and 4.99), while TIMP3, S100A12, and BDNF were the top three targets that showed higher levels in serum (log2 plasma vs. serum fold change: ‐2.91, ‐2.66, and ‐2.42). Notably, Aβ42, p‐tau181, p‐tau217, and p‐tau231 levels were significantly higher in plasma than in serum (p <0.001). Contrarily, GFAP and NEFL levels were similar in plasma and serum (p >0.05). Serum ACHE (AUC: 0.874, 95% CI: 0.768‐0.981), plasma IGF1R (AUC: 0.874, 95% CI: 0.760‐0.989), and plasma ACHE (AUC: 0.842, 95% CI: 0.703‐0.982) were the top three non‐traditional targets that distinguished between AD and control individuals.ConclusionNULISAseq‐based AD blood biomarkers in paired plasma and serum are highly correlated; however, the absolute levels significantly vary by matrix type. These findings highlight the importance of considering specimen type in clinical study designs to ensure the reliability and accuracy of AD biomarker diagnostics.

ABSTRACT If affectionate communication is beneficial for romantic relationships, as multiple investigations have shown, is it better for partners to have a higher average level of affectionate communication, or is it preferable if their levels match (even if they are both low)? The current study examined 141 romantic dyads (N = 282) composed of heterosexual adults living in the United States and they were asked to report their trait affectionate communication (i.e. expressed and received) and relationship quality (i.e. relational quality, satisfaction, commitment, intimacy, trust, passion, and love). Testing predictions drawn from affection exchange theory (AET), the study found that men’s and women’s trait expressed and received affection were positively correlated in romantic dyads, and that received affection correlations were stronger in genuine couples than in randomly paired ones (but not for expressed affection). Examining actor-partner effects expressed and received affection produced significant actor effects for men and women with all outcomes (with a small number of exceptions). Significant partner effects occurred for about half of the tests. The main finding, and focus of the study, showed that having higher average dyadic affection scores (as supported by AET) is significantly more impactful for relational quality (love and commitment aside) than having similar levels of trait affectionate communication (as supported by the theoretical principle of assortative mating). In other words, the absolute level of affectionate communication in a relationship has greater significance on relational quality than the relative levels between partners.

The metaverse provides an immersive, interactive medium for health education, but most studies evaluate immersion and gamification together. Randomized evidence disentangling their separate effects on immediate learning and short-term retention in breast health education is lacking. To isolate the effects of gamification, over and above an identical immersive metaverse environment, on immediate gains and 4-week retention of women's breast health knowledge. This two-arm parallel individually randomized controlled trial was conducted in Hangzhou, China. Eligible participants were women aged ≥18 years who were interested in breast health and able to use a personal computer with internet access. A total of 80 women were recruited via the Xiaohongshu social media platform; 8 withdrew before randomization or did not complete the baseline assessment, and the remaining 72 women were randomized to a Gamified Metaverse (GM) or a Non-Gamified Metaverse (NGM) group using a computer-generated 1:1 sequence. Both groups used the Mammoverse platform with identical educational content and exposure time. Breast health knowledge was assessed at baseline (T1), immediately post-intervention (T2), and 4-week follow-up (T3) using the same questionnaire, the primary outcome was change in knowledge score. Using linear mixed-effects models, with age, education, family history of breast cancer, prior training, and baseline knowledge as covariates. Participants and investigators were not blinded. All randomized participants completed follow-up and were included in the analysis (GM group n=36; NGM group n=36), with no loss to follow-up. Knowledge scores improved in both groups, but gains from T1 to T2 were larger in GM than NGM (Hedges g=0.65, 95% CI 0.18-1.12, p=.007). From T2 to T3, there was no between-group difference in change scores (p=.91). However, at 4 weeks GM retained higher absolute knowledge than NGM (estimated marginal means 15.7 vs 13.0). No intervention-related adverse events were reported. This study marks the first application of gamification in BSE education for ordinary Chinese women within a 3D desktop metaverse. By comparing gamified and non-gamified versions under identical metaverse platform conditions, it expands the application boundaries of gamified metaverses in breast health education. Gamification significantly enhanced immediate acquisition of breast health knowledge but did not provide additional advantages for short-term retention. However, the gamified group maintained higher absolute knowledge levels at the 4-week follow-up. Overall, in the 3D desktop metaverse, immersive experiences provide foundational effects, while gamification delivers immediate gains. To further optimize long-term retention, memory consolidation strategies must be integrated into the gamified framework. This trial was retrospectively registered at ClinicalTrials.gov (Identifier: NCT06930898, URL: https://clinicaltrials.gov/study/NCT06930898, registered on 8 April 2025).

The relationship between leptin levels and psychiatric disorders has been studied more extensively in adults than in children and adolescents. However, the results are conflicting.We investigated serum leptin levels in children and adolescents (11 to 18.9 years) with psychiatric disorders (n = 363). Absolute and relative (body-mass-index (BMI)-, sex- and pubertal-stage-adjusted z-scores using reference values of healthy children and adolescents) leptin levels of different patient groups according to diagnosis were compared. The association between leptin levels and depression (Beck Depression Inventory-II) and anxiety (Child Behavior Checklist and Youth Self Report) was examined using regression analysis.Leptin z-scores were higher in patients with psychiatric disorders than in healthy controls (median 1.50, p < .001). While global tests suggested differences in leptin z-scores between patients with different psychiatric disorders, these differences could not be attributed to diagnosis groups in post-hoc pairwise comparisons. Absolute leptin levels differed between psychiatric disorders (p < .001). Patients with anorexia nervosa (AN) had the lowest levels, and patients with mood disorders had higher leptin levels than patients with mental disorders other than mood disorders, anxiety or AN. Neither absolute nor relative leptin levels were related to depressive or anxiety symptoms in regression models adjusted for sex and BMI.Significantly elevated BMI-, sex- and puberty-stage-adjusted leptin levels were observed in children and adolescents with psychiatric disorders compared to a reference sample. Further controlled studies are needed to confirm and explain this finding. No relationship was found between absolute or relative leptin levels and symptoms of depression or anxiety.

Donor-derived cell-free DNA associated with increased risk of chronic lung allograft dysfunction and mortality: Are absolute levels better than percentage?

Association Between Air Pollution and Monday Peak Mortality From Acute Myocardial Infarction.

Conventional economic theory assumes that the well-being and happiness of individuals are solely impacted by their income levels. With the influence of behavioral economics, it is evident that personal happiness is affected by others’ possessions, previous experiences, and anticipated future outcomes as well. Accordingly, this article examines the relationship between income, social comparisons and happiness in Türkiye based on the 2024 Life Satisfaction Survey dataset. To this end, the factors indicating the absolute and relative position of individuals were classified into four categories and a social comparison measure called “lifestyle comparison” was created. The effect of these factors on happiness was estimated using the generalized ordered logit model. The findings demonstrate that relative position has as strong an effect as absolute income level among the determinants of individual happiness in Türkiye. Unlike to the existing literature, it was noted that the significance assigned to the living conditions of others, framed as the “lifestyle comparison” variable and viewed as an external comparison standard, plays a crucial role in individual happiness. It was also disclosed that an individual’s future economic expectations and economic shifts they have faced over the past year influence their levels of happiness. Overall, this research demonstrates that economic indicators in Türkiye shape individuals’ well-being through both objective and subjective effects.

Relationship between Disease Activity and Absolute Eosinophil Count and Serum IgE Level in Pediatric Patients with Eosinophilic Esophagitis

This study aimed to evaluate urinary C-megalin in relation to disease staging and diagnostic accuracy in Indian patients with type 2 diabetes mellitus (T2DM). In this cross-sectional study, 325 participants were classified into No-DKD, early-DKD, and late-DKD based on kidney disease improving global outcomes (KDIGO) criteria. Urinary C-megalin was quantified by enzyme-linked immunosorbent assay (ELISA) as absolute and creatinine-normalized values. Group comparisons, correlation analyses, and multinomial logistic regression were performed to assess associations with disease stage. Creatinine-normalized C-megalin excretion was higher in early-DKD compared with No-DKD (median 125.0 vs. 92.0 ng/mg Cr; p = 0.02) and independently associated with early disease [odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.03-1.55; p = 0.02). In late-DKD, absolute C-megalin levels were significantly associated with disease status (OR = 1.23, 95% CI: 1.02-1.48; p = 0.03), while normalized values lost significance. Diagnostic evaluation showed moderate accuracy for detecting early-DKD [area under curve (AUC): 0.69, 95% CI: 0.62-0.76, p = 0.001). Urinary C-megalin demonstrates stage-dependent diagnostic behavior in DKD, suggesting potential as a complementary marker for early tubular injury and advanced disease in high-risk diabetic populations.

ABSTRACTAging is an inevitable consequence for all organisms. According to the mitochondrial free radical theory of aging (MFRTA), reactive oxygen species (ROS), which are predominantly generated in mitochondria, are assumed to play a key role. Calorie restriction (CR) delays aging by improving mitochondrial function; however, the molecular mechanisms underlying the effects of ROS and CR on mitochondria remain poorly understood. Oxidative protein modifications in mitochondrial proteins from the heart and cerebrum of young (6.5 months) and old (27 months) rats were quantified and the effects of short‐term and lifelong CR interventions were investigated. Mass spectrometry was leveraged to achieve an unbiased and comprehensive analysis of various types of oxidative postranslational modifications (oxPTMs). Contrary to the MFRTA, aging did not cause significant increases in mitochondrial protein oxidation in the heart and cerebrum. CR markedly diminished the overall level of oxPTMs in the heart, particularly in transmembrane proteins. Similarly, the level of oxidative modification of transmembrane proteins in cerebrum was reduced by CR, whereas it perplexingly increased in mitochondrial proteins. The absolute level of oxidized mitochondrial protein was always higher in the heart than in the cerebrum under all conditions. Carbonylation, a prevalent marker of protein oxidation and aging, increased in the heart with age and was notably reduced by CR. However, this trend was not consistent in cerebrum or for some other types of oxPTMs. Therefore, protein oxidation in the heart and cerebrum exhibits distinct responses to chronological aging and dietary interventions, with the latter exerting a stronger influence.

Hypertension is a multifactorial and heterogeneous disease that remains the leading cause of global morbidity and mortality. Traditional diagnostic approaches based on office blood pressure (BP) thresholds fail to capture the dynamic variability of BP and its clinical implications. This narrative review synthesizes current evidence on hypertension phenotypes, sustained, masked, white-coat, non-dipper, and resistant, and their associations with target organ damage (TOD) affecting the heart, kidneys, brain, vasculature, and retina. A phenotype-based understanding reveals that the temporal pattern and circadian behavior of BP, rather than its absolute level alone, determine the risk and distribution of organ injury. Sustained and masked hypertension are strongly linked to left ventricular hypertrophy, microalbuminuria, and cerebrovascular disease, whereas non-dipping and resistant forms contribute disproportionately to nocturnal organ damage and renal dysfunction. White-coat hypertension, although previously deemed benign, carries a modest but measurable long-term cardiovascular risk. Advances in diagnostic modalities, including ambulatory and home BP monitoring, cardiac and vascular imaging, and biomarker profiling, have enabled early identification of subclinical TOD. Treatment strategies are evolving toward phenotype-guided management, integrating chronotherapy, targeted pharmacologic combinations, and emerging device-based interventions such as renal denervation and baroreceptor activation therapy. Future directions emphasize precision medicine approaches, combining digital health technologies, multi-omic data, and artificial intelligence–driven analytics to personalize therapy and prevent irreversible organ injury. Recognition of hypertension as a spectrum of biological phenotypes rather than a uniform disease represents a paradigm shift toward individualized cardiovascular protection and optimized long-term outcomes.

Cancer ranks second among the causes of mortality in Russia, surpassed only by cardio-vascular diseases. However, cancer incidence rates vary significantly across the country, reflecting differences in natural conditions, environmental factors, socio-economic characteristics, and population lifestyles. The aim of this study is to identify regional differences in the structure of cancer incidence in Russia using a territorial-structural approach and cartographic methods, as well as to define priority areas for the development of targeted prevention programs. The analysis covers statistical data for the period 2014–2023, including standardized incidence rates and the dynamics of various types of malignant neoplasms. Cartographic models developed in the study revealed the spatial distribution of major cancer types and identified regions with a high concentration of specific malignancies. The internal structure of cancer incidence within regions and its temporal dynamics proved to be more informative indicators than absolute incidence levels. The study made it possible to distinguish territorial types of cancer incidence structures and to assess the influence of environmental and socio-demographic factors on the spatial distribution of cancer cases across the country. The findings provide a basis for optimizing regional prevention and healthcare strategies aimed at reducing cancer mortality and improving population health under conditions of pronounced spatial heterogeneity in risk factors and disease patterns. The proposed approach allows for more efficient resource allocation, the development of targeted primary and secondary prevention strategies, and timely responses to changes in environmental and socio-economic conditions.

The age-related dynamics of main subsets of blood lymphocytes in children has been studied quite well, but the issue of the limits of reference values, especially at an early age, remains actual and important. The paper analyzes results of a direct study dataset of 624 blood samples of healthy children aged 1 week to 17 years and 11 months, residents of Moscow and the central Russian regions who underwent a clinical blood count during routine checkups. The main criterion for the complete inclusion of a child into the study was reliable information about the absence of acute and chronic health disorders. The absolute number of lymphocytes was determined as a complex of indices obtained of automated blood analysis, using 5 Diff technology of flow hemocytometry with fluorescent staining of nucleic acids. The percentage and absolute values of T lymphocytes, T helper cells, T cytotoxic cells, the ratio of helper/cytotoxic lymphocytes, as well as percentages and absolute numbers of B lymphocytes and natural killers were determined in residual blood samples by flow cytometry with 3-4 color staining. 14 age groups were formed with the number of cases from 40 to 64 in each group. The Kolmogorov–Smirnov method confirmed the normal distribution of the obtained numerical indicators, both in the general group and in all distinct age groups. The article provides detailed results of processing the data obtained using nonparametric (median, interquartile range, range from 10 to 90 centiles) and parametric (mean and standard deviation) statistics methods. Based on an estimate of the range of 10-90 centiles, the normal limits for the percentages and absolute values of the main lymphocyte subpopulations were calculated. We have been confirmed the well-known trend for a gradual decrease in the absolute number of lymphocytes and absolute values for all major subpopulations, as well as relatively higher indices of helper/cytotoxic ratio in early age groups. A higher percentage of B lymphocytes was detected in children in the age groups from 2 months to 2 years, which, together with a high total number of lymphocytes, determined fairly high absolute B cell counts in these age groups. The proposed normal ranges were validated on an independent group of 75 children aged 2 to 18 years. The individual indexes of the children in the validation group exceeded the reference values in 4 cases (5.3%, with acceptable level of discrepancies &lt; 10%), which allows us to consider the norms validated. The most debatable findings concern a relatively high absolute level of В lymphocytes in young children which is, however, in good agreement with the pooled data of the world-wide meta-analysis data. The proposed normal ranges are designed in a form that is convenient for practical use.

Abstract This paper is an empirical study aimed at examining how the main profitability ratios relate to the market capitalisations of the three top banks in the Indian privatised sector: ICICI Bank, Axis Bank, and Kotak Mahindra Bank. The analysis relies on the five years from FY 2021 to FY 2025 using secondary data, where market capitalisation is taken to be the dependent variable and four profitability measures, namely Return on Assets (ROA), Return on Equity (ROE), Net Interest Margin (NIM), and Net Profit, are used as independent variables. Both aggregate and individual bank descriptive statistics, correlation analyses, and simple linear regression models were used. The findings indicate that Net Profit is the best predictor of market capitalisation by a long way. The Net Profit variable has a very strong positive correlation with market capitalisation (explaining almost 74% of the variation) and, in the overall regression, has much stronger explanatory power than either ROA or ROE, and very weak explanatory power in comparison with NIM. The Bank-wise regressions affirm the prevailing Net Profit, with the highest R across all three banks, and predict with high predictive power for ICICI Bank. The weighted scoring system, which combines overall R2, average bank-wise R2, correlation strength, and statistical significance rates, ranks Net Profit as the best indicator, with a flawless composite score, far above ROA, ROE, and NIM. The implications of the findings include that the capitalization of banks in equity markets is more related to the absolute level of earnings rather than the efficiency ratios in isolation, and have a direct implication for the management of the banks and their investors, and analysts in the development of valuation models, performance measures, and strategic focus. Keywords Net profit; market capitalisation; profitability indicators; ROA; ROE; NIM; Indian private sector banks; ICICI Bank; Axis Bank; Kotak Mahindra Bank; regression analysis

The complex crosstalk between the tumor milieu, including the hormonal environment and immune system interactions, is important to tumor growth in endometrial cancer (EC). Estradiol-mediated estrogen receptor α (ERα) signaling is critical for the function of regulatory tumor-infiltrating lymphocytes (TILs) in patients with cervical cancer. Therefore, the present study investigated the relative ERα level in infiltrating lymphocytes derived from EC tissues and whether its variable expression is associated with clinicopathological features, including the molecular classification. Endometrial tumor and normal endometrium samples were collected from 82 patients diagnosed with EC; however, only 54 samples were assessed as sufficient and qualified for further study. The frequency of T helper lymphocytes (Th cells), cytotoxic T lymphocytes (CTLs) and B lymphocytes (B cells) as well as the percentages of these cells expressing ERα were examined using flow cytometry. Furthermore, the expression of ERα in these TIL subpopulations was evaluated using median fluorescence intensity (MFI) to assess the absolute level of ERα in the studied lymphocytes. Associations of ERα levels in TILs with clinicopathological characteristics, including molecular subtypes, were measured. All the studied TIL subpopulations showed a significantly lower ERα level compared with normal endometrial tissue, which constituted the control group. However, the frequencies of Th cells and Th cells expressing ERα were significantly increased, while the frequencies of CTLs and CTLs expressing ERα were significantly decreased in EC compared with the control. The frequency of B cells expressing ERα was significantly increased in high grade EC tumors and tumors harboring mismatch repair deficiency. ERα expression (demonstrated with MFI) on examined TIL subsets was negatively correlated with body mass index in patients but did not demonstrate other correlations with the examined clinicopathological prognostic factors. The mechanism of ERα decrease in TILs from endometrial tumors as well as its prognostic significance and potential role in therapeutic targeting needs further investigation, including further examination of its molecular background and functional validation experiments.

To systematically investigate the rheumatic disease spectrum associated with anti-PM/Scl antibodies and to clarify their clinical significance in idiopathic inflammatory myopathies (IIM). Patients who were tested positive for anti-PM/Scl antibodies by immunoblotting at Peking University People' s Hospital from January 2016 to December 2024 were enrolled. Clinical and immunolo gical data were systematically collected and compared across the subgroups defined by anti-PM/Scl75, anti-PM/Scl100, or dual antibody positivity. A total of 422 anti-PM/Scl-positive patients were enrolled. Among them, 83.2% (351/422) were diagnosed with connective tissue disease (CTD), 7.8% (33/422) were not diagnosed with CTD, and 9.0% (38/422) had an undetermined clinical diagnosis. Among 422 patients, most commonly represented by IIM (19.7%), systemic sclerosis (SSc, 14.2%), overlap syndrome (11.8%), undifferentiated CTD (UCTD, 10.4%), rheumatoid arthritis (6.9%), Sjögren syndrome (6.4%), and systemic lupus erythematosus (6.2%), the remaining diseases accounting for 24.4%. Within the IIM subgroup, dermatomyositis predominated (74.7%), followed next by anti-synthetase syndrome (21.7%) and immune-mediated necrotizing myopathy (3.6%). Anti-PM/Scl75 antibodies were detected in 52.1% (220/422) of the total patients, anti-PM/Scl100 in 43.6% (184/422), and both in 4.3% (18/422). In the subsequent detailed analysis of the anti-PM/ Scl-positive subgroup, double-positive patients showed a significantly higher prevalence of SSc (38.9% vs. 14.1% vs. 12.0%, P=0.015) and interstitial lung disease (ILD, 70.6% vs. 28.8% vs. 35.4%, P=0.002) than those individuals with single antibody positivity alone. Raynaud phenomenon was observed more frequently in both the double-positive and anti-PM/Scl75-positive groups than in the anti-PM/Scl100-positive group (29.4% vs. 21.3% vs. 10.9%, P=0.007). The measured proportion of peri-pheral CD8+ T cells was also higher in double-positive patients (35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%, P= 0.008), whereas absolute regulatory T-cell levels were lower in the anti-PM/Scl75-positive group compared directly with the anti-PM/Scl100-positive group [7.6% (5.4%, 10.9%) vs. 9.0% (7.9%, 12.0%) vs. 8.8% (5.2%, 9.7%), P=0.017]. Additionally, co-positivity for anti-PM/Scl and other myositis- specific or myositis-associated antibodies was strongly associated with an increased frequency of ILD (P < 0.05). Anti-PM/Scl antibodies define a broad disease spectrum encompassing IIM, SSc, overlap syndromes, and UCTD. Dual positivity for anti-PM/Scl75 and anti-PM/Scl100 identifies patients prone to systemic sclerosis and pulmonary involvement, suggesting additive pathogenic effects of the two antibody specificities.

Based on field investigations in multiple irrigation districts, it was found that farmers frequently employ sandbag barriers or direct pumping to meet irrigation demands, disrupting irrigation schedules and destabilizing downstream water supply. The core issue stems from differential deterioration of canal sections after prolonged operation, causing variations in Manning’s roughness coefficient and seepage rates. Consequently, irrigation plans based on historical experience no longer satisfy water-level accuracy requirements. This study focuses on a typical canal system in the Ningxia Yellow River Irrigation District, utilizing the NSGA-II optimization algorithm to simultaneously calibrate Manning’s roughness coefficient and seepage parameters. The results indicate that Manning’s roughness exhibits significant spatial heterogeneity in canal sections constructed with the same technique after several years of operation; the simulated values at three water level control sections generally align with the measured trends, with absolute water level errors within 0.03 m; through accurate parameter identification and combined with AMR adaptive mesh refinement technology, the canal flow process is precisely simulated, enabling timely irrigation schedule adjustments to resolve the aforementioned conflicts.; by assessing canal section deterioration and prioritizing anti-seepage measures, corn irrigation area is projected to expand by over 3.2 hectares. This research holds significant practical value for enhancing water resource utilization efficiency, boosting agricultural productivity, and advancing sustainable development in irrigation districts. Future efforts could integrate water inflow predictions, crop water requirements, and coordinated control of gate groups to establish a digital twin-driven precision irrigation framework for the entire canal system.