Probing the Surface Layer Modulation on Archaeal Mechanics and Adhesion at the Single-Cell Level.

Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.

CircSSBP2 acts as a MiR-2400 sponge to promote intramuscular preadipocyte proliferation by regulating NDRG1.

Intramuscular fat (IMF) is a critical factor in beef quality. IMF is mainly distributed between muscle fibres and its accumulation can affect the marbling and meat quality of beef. IMF formation and deposition is a complex process and in recent years a group of non-coding RNAs (ncRNAs), known as circRNAs, have been discovered to play an important role in regulating intramuscular fat deposition. CircRNAs form a covalent loop structure after reverse splicing of precursor mRNAs. They can act by adsorbing miRNAs, thereby reducing their repressive effects on downstream target genes. Based on high-throughput sequencing of circRNAs in intramuscular fat of Qinchuan and Japanese black cattle, we identified a novel circSSBP2 that is differentially expressed between the two species and associated with adipogenesis. We show that circSSBP2 knockdown promotes bovine intramuscular preadipocyte proliferation, whereas overexpression inhibits bovine intramuscular preadipocyte proliferation. We also show that circSSBP2 can act as a molecular sponge for miR-2400 and that miR-2400 overexpression promotes bovine intramuscular preadipocyte proliferation. Furthermore, N-myc downstream-regulated gene 1 (NDRG1) was identified as a direct target gene of miR-2400, and NDRG1 interference promoted the proliferation of bovine intramuscular preadipocytes. In conclusion, our results suggest that circSSBP2 inhibits the proliferation of bovine intramuscular preadipocytes by regulating the miR-2400/NDRG1 axis.

Tumor-Targeted Oxaliplatin(IV) Prodrug Delivery Based on ROS-Regulated Cancer-Selective Glycan Labeling.

Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.

NANOG regulate the JAK/STAT3 pathway to promote trophoblast cell migration and epithelial-mesenchymal transition (EMT) in hypertensive disorders of pregnancy (HDP) through protein interaction with CDK1.

PROBLEM: Hypertensive disorders of pregnancy (HDP) are a common pregnancy disease. NANOG and Cyclin-dependent kinase 1 (CDK1) are essential for regulating the function of cell proliferation and apoptosis. However, the mechanism of action in HDP is yet unclear. METHOD: The microarray dataset GSE6573 was downloaded from the GEO database. Emt-related gene set was downloaded from Epithelial-Mesenchymal Transition gene database 2.0 were screened differentially expressed genes by bioinformatics analysis. Pathway Commons and Scansite 4.0 databases were used to predict the interaction between proteins. Placental tissue samples were collected from HDP patients and patients with uneventful pregnancies. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of NANOG, CDK1, MMP-2, MMP-9, EMT markers and the JAK/STAT3 pathway proteins. Transfection NANOG overexpression/knockdown, and CDK1 knockdown into the human chorionic trophoblast cells (HTR-8/Svneo). CCK-8, Transwell and Wound-healing assay were used to evaluate cell proliferation, invasion and migration. CO-IP and GST pull-down assays were used to confirm the protein interaction. RESULTS: A total obtained seven EMT-related differentially expressed genes, wherein NANOG, NODAL and LIN28A had protein interaction. In the HDP patients' tissue found that NANOG and CDK1 had lower expression. NANOG overexpression promoted HTR-8/Svneo proliferation, migration and EMT, while NANOG knockdown had the opposite effect. Further a protein interaction between STAT3 and CDK1 with NANOG. NANOG overexpression downregulated the JAK/STAT3 pathway to promote HTR-8/Svneo proliferation, migration and EMT, which was reversed by CDK1 knockdown. CONCLUSIONS: NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.

Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

In Situ Species Analysis of a Lithium-Ion Battery Electrolyte Containing LiTFSI and Propylene Carbonate.

In this study, we analyzed the species in a model electrolyte consisting of a lithium salt, lithium bis(trifluoromethane sulfone)imide (LiTFSI), and a widely used neutral solvent propylene carbonate (PC) with excess infrared (IR) spectroscopy, ab initio molecular dynamics simulations (AIMD), and quantum chemical calculations. Complexing species including the charged ones [Li+(PC)4, TFSI-, TFSI-(PC), TFSI-(PC)2, and Li(TFSI)2-] are identified in the electrolyte. Quantum chemical calculations show strong Li+···O(PC) interaction, which suggests that Li+ would transport in the mode of solvation-carriage. However, the interaction energy of each hydrogen bond in TFSI-(PC) is very weak, suggesting that TFSI- would transport in hopping mode. In addition, the concentration dependences of the relative population of the species were also derived, providing a scenario for the dissolving process of the salt in PC. These in-depth studies provide physical insights into the structural and interactive properties of the electrolyte of lithium-ion batteries.

Lanthanide-Sensitized Upconversion Iridium Complex via Triplet Energy Transfer.

Cyclometalated iridium (Ir) complexes demonstrate impressive capabilities across a range of fields, including biology and photocatalysis, due to their tunable optical characteristics and structure flexibility. However, generating upconversion luminescence of Ir complexes under near-infrared light excitation is challenging. Herein, by employing lanthanide-doped upconversion nanoparticles (UCNPs) as the sensitizer, a new strategy is demonstrated to gain upconversion luminescence of Ir complexes via triplet energy transfer. This design relies on a rationally designed hybrid of core-shell structured NaYbF4:Tb@NaTbF4 UCNPs and new Ir phosphonate complexes, in which UCNPs can migrate upconverted energy to the surface of nanoparticles through Tb3+-mediated energy migration and then sensitize the upconversion luminescence of Ir complexes upon 980 nm excitation. Both experimental and theoretical investigations highlight the significance of triplet energy transfer from excited Tb3+ ions to the triplet state of Ir complexes in the sensitization of upconversion luminescence of Ir complexes. These findings may open exciting avenues for fabricating hybrid Ir materials with new functions and driving the development of UCNP-based nanomaterials.

Development and validation of a sensitive LC-MS/MS assay of GT-14, a novel Gαi2 inhibitor, in rat plasma, and its application in pharmacokinetic study.

A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gαi2 inhibitor, GT-14, in rat plasma using a SCIEX 6500+ triple QUAD LC-MS system equipped with an ExionLC UHPLC unit. GT-14 (m/z 265.2 → 134.1) and griseofulvin (Internal Standard, IS) (m/z 353.1 → 285.1) were detected in a positive mode by electrospray ionization (ESI) using multiple reaction monitoring (MRM). The assay was linear in the concentration range of 0.78-1000 ng/mL in rat plasma. Both accuracy and precision values were within the acceptance criteria of ±15 %, as established by FDA guidance. The matrix effect was negligible from plasma, with signal percentages of 98.5-106.9 %. The mean recovery was 104.5 %, indicating complete extraction of GT-14 from plasma. GT-14 was found to be stable under different experimental conditions. The validated method was successfully applied to evaluate plasma protein binding and in vivo pharmacokinetics of GT-14 in rats.

Effects of Lactobacillus plantarum fermentation on the structure, physicochemical properties, and digestibility of foxtail millet starches.

This study investigated the effects of Lactobacillus plantarum fermentation on the structural, physicochemical, and digestive properties of foxtail millet starches. The fermented starch granules formed a structure with honeycomb-like dents, uneven pores, and reduced particle size. As the fermentation time extended, the amylose content of waxy (0.88 %) and non-waxy (33.71 %) foxtail millet starches decreased to the minimum value at 24 h (0.59 % and 29.19 %, respectively), and then increased to 0.85 % and 31.87 % at 72 h, respectively. Both native and fermented foxtail millet starches exhibited an A-type crystal structure. Compared with native samples, the fermented samples performed enhanced proportion of short-branched chain, crystallinity, and short-range ordered degree. After fermentation for 24 h, the solubility, adsorption capacity, and pasting viscosity of foxtail millet starches improved, whereas the swelling power, pasting temperature, breakdown, setback, and degree of retrogradation reduced. Additionally, fermentation increased the transition temperatures, enthalpy, and digestibility. Overall, Lactobacillus plantarum fermentation is considered a competent choice to regulate the characteristics of foxtail millet starch.

Biochar-derived dissolved organic matter enhanced the release of residual ciprofloxacin from the soil solid phase.

Biochar has been utilized to reduce ciprofloxacin (CIP) residues in soil. However, little is known about the effect of biochar-derived dissolved organic matter (DOM) on residual CIP transformation. Thus, we analyzed the residual soil CIP as influenced by biochar generated from rice straw (RS3 and RS6), pig manure (PM3 and PM6), and cockroach shell (CS3 and CS6) at 300 °C and 600 °C. The three-dimensional excitation-emission matrix (3D-EEM), parallel factor analysis (PARAFAC) and two-dimensional correlation spectral analysis (2D-COS) were used to describe the potential variation in the DOM-CIP interaction. Compared with CK, biochar amendment increased the water-soluble CIP content by 160.7% (RS3), 55.2% (RS6), 534.1% (PM3), 277.5% (PM6), 1160.6% (CS3) and 703.9% (CS6), indicating that the biochar feedstock controlled the soil CIP release. The content of water-soluble CIP was positively correlated with the content of dissolved organic carbon (r = 0.922, p < 0.01) and dissolved organic nitrogen (r = 0.898, p < 0.01), suggesting that the major influence of the water-soluble CIP increase was DOM. The fluorescence quenching experiment showed that the interaction between DOM and CIP triggered static quenching and the creation of a DOM complex. The mean log K of protein-like material (4.977) was higher than that of terrestrial humus-like material (3.491), suggesting that the protein-like material complexed CIP was more stable than the humus-like material. Compared with pyrolysis at 300 °C, pyrolysis at 600 °C decreased the stability of the complex of protein-like material and CIP by 0.44 (RS), 1.689 (PM) and 0.548 (CS). This result suggested that the influence of temperature change was more profound on PM biochar-derived DOM than on RS and CS. These insights are essential for understanding CIP transportation in soil and controlling CIP contamination with biochar.

The prognostic genes model of breast cancer drug resistance based on single-cell sequencing analysis and transcriptome analysis.

Breast cancer (BC) represents a multifaceted malignancy, with escalating incidence and mortality rates annually. Chemotherapy stands as an indispensable approach for treating breast cancer, yet drug resistance poses a formidable challenge. Through transcriptome data analysis, we have identified two sets of genes exhibiting differential expression in this context. Furthermore, we have confirmed the overlap between these genes and those associated with exosomes, which were subsequently validated in cell lines. The investigation screened the identified genes to determine prognostic markers for BC and utilized them to formulate a prognostic model. The disparities in prognosis and immunity between the high- and low-risk groups were validated using the test dataset. We have discerned different BC subtypes based on the expression levels of prognostic genes in BC samples. Variations in prognosis, immunity, and drug sensitivity among distinct subtypes were examined. Leveraging data from single-cell sequencing and prognostic gene expression, the AUCell algorithm was employed to score individual cell clusters and analyze the pathways implicated in high-scoring groups. Prognostic genes (CCT4, CXCL13, MTDH, PSMD2, and RAB27A) were subsewoquently validated using RT-qPCR. Consequently, we have established a model for predicting prognosis in breast cancer that hinges on drug resistance and ERGs. Furthermore, we have evaluated the prognostic value of this model. The genes identified as prognostic markers can now serve as a reference for precise treatment of this condition.

GAS5 regulated by FTO-mediated m6A modification suppresses cell proliferation via the IGF2BP2/QKI axis in breast cancer.

BACKGROUND: The lncRNA growth arrest-specific 5 (GAS5) is involved in regulating breast cancer progression. In this study, we aimed to elucidate the function and mechanism of GAS5 in breast cancer. METHODS: The expressions of GAS5, fat mass and obesity-associated protein (FTO), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and Quaking (QKI) were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. The m6A modification level of GAS5 was detected using m6A immunoprecipitation assay (MeRIP). The interaction between IGF2BP2 and GAS5 or QKI was detected using RNA immunoprecipitation assay (RIP) and dual luciferase reporter assay. Cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) assay. The biological functions of the FTO/GAS5/IGF2BP2/QKI axis was assessed using the tumor xenograft assay. RESULTS: LncRNA GAS5 expression decreased in breast cancer and was regulated by FTO-mediated m6A modification in an IGF2BP2-dependent manner, resulting in decreased GAS5 stability and expression. GAS5 recruited IGF2BP2 to target QKI and upregulated QKI expression in breast cancer cells. GAS5 suppressed breast cancer growth via IGF2BP2/QKI, and this inhibitory effect was modulated by FTO both in vitro and in vivo. CONCLUSIONS: GAS5 regulated by FTO-mediated m6A modification represses the growth of breast cancer via the IGF2BP2/QKI pathway, suggesting that the FTO/GAS5/IGF2BP2/QKI pathway can be a potential target for breast cancer treatment.

Analysis of the factors influencing of sleep quality in intensive care unit awake patients based on a structural equation model: A cross-sectional study.

OBJECTIVE: The objective of this study was to construct and validate a structural equation model (SEM) to identify factors associated with sleep quality in awake patients in the intensive care unit (ICU) and to assist in the development of clinical intervention strategies. RESEARCH METHODS/SETTING: In this cross-sectional study, 200 awake patients who were cared for in the ICU of a tertiary hospital in China were surveyed via several self-report questionnaires and wearable actigraphy sleep monitoring devices. Based on the collected data, structural equation modelling analysis was performed using SPSS and AMOS statistical analysis software. The study is reported using the STROBE checklist. RESULTS: The fit indices of the SEM were acceptable: χ2/df = 1.676 (p < .001) and RMSEA = .058 (p < 0.080). Anxiety/depression had a direct negative effect on the sleep quality of awake patients cared for in the ICU (ß = -.440, p < .001). In addition, disease-freeness progress had an indirect negative effect on the sleep quality of awake patients cared for in the ICU (ß = -.142, p < .001). Analgesics had an indirect negative effect on the sleep quality of awake patients cared for in the ICU through pain and sedatives (ß = -.082, p < .001). Sedation had a direct positive effect on the sleep quality of conscious patients cared for in the ICU (ß = .493; p < .001). CONCLUSION: The results of the SEM showed that the sleep quality of awake patients cared for in the ICU is mainly affected by psychological and disease-related factors, especially anxiety, depression and pain, so we can improve the sleep quality of patients through psychological intervention and drug intervention.

Analysis of the perivascular fat attenuation index and quantitative plaque parameters in relation to haemodynamically impaired myocardial ischaemia.

To investigate the correlation between quantitative plaque parameters, the perivascular fat attenuation index, and myocardial ischaemia caused by haemodynamic impairment. Patients with stable angina who had invasive flow reserve fraction (FFR) assessment and coronary artery computed tomography (CT) angiography were retrospectively enrolled. A total of 138 patients were included in this study, which were categorized into the FFR < 0.75 group (n = 43), 0.75 ≤ FFR ≤ 0.8 group (n = 37), and FFR > 0.8 group (n = 58), depending on the range of FFR values. The perivascular FAI and CTA-derived parameters, including plaque length (PL), total plaque volume (TPV), minimum lumen area (MLA), and narrowest degree (ND), were recorded for the lesions. An FFR < 0.75 was defined as myocardial-specific ischaemia. The relationships between myocardial ischaemia and parameters such as the PL, TPV, MLA, ND, and FAI were analysed using a logistic regression model and receiver operating characteristic (ROC) curves to compare the diagnostic accuracy of various indicators for myocardial ischaemia. The PL, TPV, ND, and FAI were greater in the FFR < 0.75 group than in the grey area group and the FFR > 0.80 group (all p < 0.05). The MLA in the FFR < 0.75 group was lower than that in the grey area group and the FFR > 0.80 group (both P < 0.05). There were no significant differences in the PL, TPV, or ND between the grey area and the FFR > 0.80 group, but there was a significant difference in the FAI. The coronary artery lesions with FFRs ≤ 0.75 had the greatest FAI values. Multivariate analysis revealed that the perivascular FAI and PL density are significant predictors of myocardial ischaemia. The FAI has some predictive value for myocardial ischaemia (AUC = 0.781). After building a combination model using the FAI and plaque length, the predictive power increased (AUC, 0.781 vs. 0.918), and the change was statistically significant (P < 0.001). The combined model of PL + FAI demonstrated great diagnostic efficacy in identifying myocardial ischaemia caused by haemodynamic impairment; the lower the FFR was, the greater the FAI. Thus, the PL + FAI could be a combined measure to securely rule out myocardial ischaemia.

LGR5 Modulates Differentiated Phenotypes of Chondrocytes Through PI3K/AKT Signaling Pathway.

BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction. However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein-protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize ß-catenin and enhance the intensity of Wnt/ß-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION: LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.

A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. METHODS: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. RESULTS: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. CONCLUSIONS: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

O-GlcNAcylation Facilitates the Interaction between Keratin 18 and Isocitrate Dehydrogenases and Potentially Influencing Cholangiocarcinoma Progression.

Glycosylation plays a pivotal role in the intricate landscape of human cholangiocarcinoma (CCA), actively participating in key pathophysiological processes driving tumor progression. Among the various glycosylation modifications, O-linked ß-N-acetyl-glucosamine modification (O-GlcNAcylation) emerges as a dynamic regulator influencing diverse tumor-associated biological activities. In this study, we employed a state-of-the-art chemical proteomic approach to analyze intact glycopeptides, unveiling the critical role of O-GlcNAcylation in orchestrating Keratin 18 (K18) and its interplay with tricarboxylic acid (TCA) cycle enzymes, specifically isocitrate dehydrogenases (IDHs), to propel CCA progression. Our findings shed light on the mechanistic intricacies of O-GlcNAcylation, revealing that site-specific modification of K18 on Ser 30 serves as a stabilizing factor, amplifying the expression of cell cycle checkpoints. This molecular event intricately fosters cell cycle progression and augments cellular growth in CCA. Notably, the interaction between O-GlcNAcylated K18 and IDHs orchestrates metabolic reprogramming by down-regulating citrate and isocitrate levels while elevating α-ketoglutarate (α-KG). These metabolic shifts further contribute to the overall tumorigenic potential of CCA. Our study thus expands the current understanding of protein O-GlcNAcylation and introduces a new layer of complexity to post-translational control over metabolism and tumorigenesis.

Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity.

Allergic rhinitis (AR) is a global health challenge that particularly affects the quality of life of children. Human rhinovirus (HRV) infection usually causes common cold in the upper respiratory tract (URT) and can also affect airway allergy development, such as asthma exacerbation, but its relationship with AR is poorly understood. The study aimed to gain insight into the characteristics of HRV that is prevalent in AR children and its role in AR severity. A total of 362 children with symptomatic AR were enrolled from southwestern China during 2022-2023, and nasal lavage samples were collected for HRV molecular characterization and cytokine measurement. HRV was detected in 40% of the AR children, with peak detection in autumn. The positive rate was not correlated with whether the subjects were under allergen-specific immunotherapy (AIT). Among the detected HRVs, 42% were species A, 36% were species B, and 22% were species C, involving 21 A genotypes, 6 B genotypes, and 7 C genotypes. HRV positivity was significantly associated with symptom severity (visual analog scale [VAS] score) and elevated levels of local nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 in AR children who did not receive antiallergic treatment. All three species of HRV strains (A1B, A21, B27, B70, and C17) had been isolated and were able to infect respiratory epithelial tissue in vitro. Complete genome sequencing showed that the antigenic epitopes of the isolated HRVs had certain variations. Our work reveals the etiological characteristics of URT-HRV in AR children and suggests a role of HRV infection in the pathogenesis of childhood AR. IMPORTANCE: Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.

An unusually high prevalence of allergic rhinitis at high altitudes in 6-7 year old children - An epidemiological study.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.