Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology.

Common respiratory viruses, including the human parainfluenza viruses, threaten human health seasonally and associate with the development of chronic lung diseases. Evidence suggests that these viruses can persist, but the sources of viral products in vivo and their impact on chronic respiratory diseases remain unknown. Using the murine parainfluenza virus Sendai, we demonstrate that viral protein and RNA persist in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells long after the infectious virus is cleared. Cells containing persistent viral protein expressed Th2 inflammation-related transcriptomic signatures associated with the development of chronic lung diseases, including asthma. Lineage tracing demonstrated that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a key factor in the progression from acute to chronic lung disease after infection with parainfluenza virus.

Comparison of Soy and Pea Protein for Cultured Meat Scaffolds: Evaluating Gelation, Physical Properties, and Cell Adhesion.

Cultured meat is under investigation as an environmentally sustainable substitute for conventional animal-derived meat. Employing a scaffolding technique is one approach to developing cultured meat products. The objective of this research was to compare soy and pea protein in the production of hydrogel scaffolds intended for cultured meat. We examined the gelation process, physical characteristics, and the ability of scaffolds to facilitate cell adhesion using mesenchymal stem cells derived from porcine adipose tissue (ADSCs). The combination of soy and pea proteins with agarose and agar powders was found to generate solid hydrogels with a porous structure. Soy protein-based scaffolds exhibited a higher water absorption rate, whereas scaffolds containing agarose had a higher compressive strength. Based on Fourier transform infrared spectroscopy analysis, the number of hydrophobic interactions increased between proteins and polysaccharides in the scaffolds containing pea proteins. All scaffolds were nontoxic toward ADSCs, and soy protein-based scaffolds displayed higher cell adhesion and proliferation properties. Overall, the soy protein-agarose scaffold was found to be optimal for cultured meat production.

Enhancing emulsion, texture, rheological and sensory properties of plant-based meat analogs with green tea extracts.

Plant-based meat analogs require improvements in taste and texture to better replicate traditional meat. L-theanine and tannin, abundant in green tea, influence food taste and physicochemical properties. This study evaluated the quality characteristics of green tea extract (GE)-supplemented plant-based patties (PP) and the mechanisms affecting taste and texture. Green tea was extracted with water (GWE) or 70 % ethanol (GEE). GEE contained higher tannin and lower L-theanine levels than GWE. Both GWE and GEE reduced protein deterioration and lipid oxidation in PP throughout the 28-day storage period. PP with 1.0 % GEE (PP-GEE1.0) showed improved emulsion stability and texture due to non-covalent interactions including hydrophobic interaction and hydrogen bonds, and increased ß-sheet structures between tannin and pea protein. PP-GEE1.0 also had superior sensory characteristics due to an optimal balance of L-theanine and tannin. Overall, the incorporation of GE, particularly GEE significantly improved physicochemical properties, sensory quality, and storage stability of PP.

Sinonasal Complications of Combined Transseptal-transnasal and Bilateral Transnasal Approaches for Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

BACKGROUND: The endoscopic combined transseptal-transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach. METHODS: Utilizing a retrospective cohort from a preeminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal-transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), Sino-Nasal Outcome Test-22 (SNOT-22), and nasal obstruction symptom evaluation (NOSE) RESULTS: The transseptal-transnasal approach exhibited reduced rates of postoperative ear fullness (p < 0.001), along with fewer subjective complaints of smell/taste loss (p = 0.022) and thick nasal discharge (p = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the two approaches (p = 0.243 and p = 0.454 for CCCRC and CCSIT, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal-transnasal approach (p = 0.067). CONCLUSION: For the surgical treatment of pituitary adenomas, the transseptal-transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation.

Effect and safety of perioperative ibuprofen administration in pediatric tonsillectomy: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of perioperative ibuprofen administration by conducting a meta-analysis of pertinent literature. METHODS: We conducted a comprehensive review of studies sourced from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases. The studies covered the period from database inception to June 2024. A perioperative ibuprofen administration group was compared to a control group administered either saline, acetaminophen, paracetamol, or opioids. The primary outcome was post-tonsillectomy bleeding that was categorized into overall bleeding and further classified as type 1 (observed at home or evaluated in the emergency department without additional intervention), type 2 (necessitating readmission for observation), and type 3 (requiring a return to the operating room for hemorrhage control). Morbidity incidence rates for postoperative nausea and vomiting were also assessed. The secondary outcomes assessed were postoperative pain management and the frequency of analgesic drug usage. Postoperative pain management was assessed from the incidence of emergency department visits or nurses' calls for pain independent of the presence or absence of dehydration. RESULTS: Twenty-two studies with 27,149 patients were included and reviewed for this meta-analysis. Post-tonsillectomy bleeding (OR = 0.9954, 95 % CI [0.8800; 1.1260], I2 = 0.0 %) was not significantly higher in the ibuprofen administration group compared to the control group. In subgroup analysis of post-tonsillectomy bleeding severity, ibuprofen caused clinically insignificant type 1 post-tonsillectomy bleeding that did not require intervention (OR = 1.1310 [0.7398; 1.7289]). Clinically significant bleeding requiring hospital admission (type 2) or surgical control (type 3) was not observed. Administration of ibuprofen has demonstrated efficacy in reducing the need for analgesic drugs (OR = 0.4734, 95 % CI [0.2840; 0.7893]; I2 = 19.8 %) and is associated with a significant decrease in the incidence of postoperative nausea and vomiting (OR = 0.4886, 95 % CI [0.3156; 0.7562], I2 = 34.3 %). CONCLUSION: This study demonstrated that administration of ibuprofen for pediatric tonsillectomy did not increase the incidence of clinically significant postoperative bleeding. Ibuprofen administration decreased the incidence and severity of postoperative pain, nausea, and vomiting.

Short-term efficacy of platelet-rich plasma in the treatment of persistent olfactory dysfunction: systematic review and meta-analysis.

PURPOSE: To assess the short-term effects of topical platelet-rich plasma (PRP) injection on persistent refractory olfactory dysfunction. METHODS: A comprehensive literature search of the PubMed, SCOPUS, EMBASE, Web of Science, Google Scholar, and Cochrane databases was conducted for articles up to November 2023. The search focused on studies that compared the amelioration of olfactory dysfunction between a topical PRP treatment cohort and a control group (receiving either placebo or no treatment), along with pre- and post-treatment comparisons. Subgroup analysis of the evaluation of olfactory function was also performed. RESULTS: The improvement in olfactory scores 1-3 months post-treatment (standardized mean difference = 1.5354 [95% confidence interval: 0.7992; 2.2716], I2 = 83.8%) was greater in the treatment group than in the control group. In the treatment group, PRP increased the threshold, discrimination, and identification (TDI) score for Sniffin' Sticks by > 5.5 (minimum clinically significant difference; mean difference = 6.1789 [3.9788; 8.3789], I2 = 0.0%), indicating clinically significant improvement based on verified examinations. The rate of significant improvement among patients was 0.6683 [0.5833; 0.7436] after treatment. All TDI subdomains were significantly and similarly improved after treatment. CONCLUSION: This meta-analysis suggests that injection of PRP into the olfactory fissure or surrounding mucosal areas is an effective treatment for persistent refractory olfactory dysfunction in the short term.

Efficacy and safety of perioperative ibuprofen for pain control after pediatric tonsillectomy: A systemic review and meta-analysis.

OBJECTIVES: To assess the safety and effectiveness of perioperative ibuprofen in pediatric tonsillectomy through a meta-analysis of relevant randomized controlled trials. METHODS: We conducted a comprehensive review of studies available in PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to June 2024. This analysis compared perioperative ibuprofen administration to control groups (saline, acetaminophen, or opioids). Outcomes assessed were postoperative pain management, as indicated by the frequency of analgesic use, and morbidity rates, which included the incidence of postoperative nausea and vomiting and post-tonsillectomy hemorrhage (PTH). PTH was further categorized as primary (occurring on the day of operation) or secondary (occurring after the day of operation), and classified as type 1 (observed at home or evaluated in the emergency department without further intervention), type 2 (requiring readmission for observation), or type 3 (necessitating a return to the operating room for hemorrhage control). RESULTS: This analysis included nine studies involving a total of 1545 patients. Incidences of primary PTH (OR = 1.0949, 95 % CI [0.4169; 2.8755], I2 = 0.0 %), secondary PTH (OR = 1.6433 95 % CI [0.7783; 3.4695], I2 = 0.1 %), and overall PTH (OR = 1.4296 95 % CI [0.8383; 2.4378], I2 = 0.0 %) were not significantly higher in the ibuprofen group than the control groups. Administration of ibuprofen led to a significant decrease in postoperative nausea and vomiting (OR = 0.4228 95 % CI [0.2500; 0.7150], I2 = 40.0 %) and frequency of postoperative analgesic uptake (OR = 0.4734 95 % CI [0.2840; 0.7893]; I2 = 19.8 %). There was no difference in bleeding by type between the ibuprofen and control groups. CONCLUSIONS: Our meta-analysis demonstrated that administration of ibuprofen for pediatric tonsillectomy did not significantly increase the incidence of postoperative bleeding but did decrease postoperative emesis and improve pain control.

The Impact of Supersaturated Electrode on Heterogeneous Lithium Nucleation and Growth Dynamics.

The concept of a lithiophilic electrode proves inadequate in describing carbon-based electrode materials due to their substantial mismatch in surface energy with lithium metal. However, their notable capacity for lithium chemisorption can increase active lithium concentration required for nucleation and growth, thereby enhancing the electrochemical performance of lithium metal anodes (LMAs). In this study, we elucidate the effects of the supersaturated electrode which has high active lithium capacity around equilibrium lithium potential on LMAs through an in-depth electrochemical comparison using two distinct carbon electrode platforms with differing carbon structures but similar two-dimensional morphologies. In the supersaturated electrode, both the dynamics and thermodynamic states involved in lithium nucleation and growth mechanisms are significantly improved, particularly under continuous current supply conditions. Furthermore, the chemical structures of the solid-electrolyte-interface layers (SEIs) are greatly influenced by the elevated surface lithium concentration environment, resulting in the formation of more conductive lithium-rich SEI layers. The improved dynamics and thermodynamics of surface lithium, coupled with the formation of enhanced SEI layers, contribute to higher power capabilities, enhanced Coulombic efficiencies, and improved cycling performances of LMAs. These results provide new insight into understanding the enhancements in heterogeneous lithium nucleation and growth kinetics on the supersaturated electrode.

Comparative Effectiveness of Dupilumab Versus Sinus Surgery for Chronic Rhinosinusitis With Polyps: Systematic Review and a Meta-Analysis.

BACKGROUND: Current treatment paradigms recommend surgical intervention when conventional medical management proves ineffective in resolving chronic rhinosinusitis with nasal polyposis. OBJECTIVES: To assess and compare the efficacy of dupilumab and functional endoscopic sinus surgery (FESS) for the treatment of chronic rhinosinusitis with nasal polyp (CRSwNP) over time. METHODS: Studies comparing CRSwNP patients who received dupilumab with those who underwent FESS were included. Outcome measures included the nasal congestion score (NCS), Sino-nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test-40 (UPSIT-40), and nasal polyp score (NPS). The risk of bias was evaluated using the Newcastle-Ottawa Scale. RESULTS: A total of 4 studies with 724 participants were included. The dupilumab group had a superior NCS, but an inferior NPS, compared to the FESS group during the follow-up period. The SNOT-22 score of the dupilumab group was inferior to that of the FESS group until 6 months posttreatment, but the scores were similar at around 1 year. A similar trend was observed for the UPSIT-40 score, but the score of the dupilumab group was higher at around 1 year. CONCLUSION: Functional endoscopic sinus surgery was more effective than dupilumab for several months after treatment. However, at 1 year after treatment, the effects of the 2 treatments became similar, with greater olfactory improvement seen in the dupilumab group.

The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial.

BACKGROUND: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. METHODS: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19-60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. RESULTS: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18-0.20) mg/kg in the male group and 0.29 (0.29-0.30) mg/kg in the female group. CONCLUSIONS: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. TRIAL REGISTRATION: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).

Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system.

BACKGROUND: Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. METHODS: This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. RESULTS: Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. CONCLUSIONS: We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.

Surgical and Regenerative Treatment Options for Empty Nose Syndrome: A Systematic Review.

OBJECTIVES: Patients with empty nose syndrome typically experience paradoxical nasal congestion, nasal dryness, epistaxis, and suffocation. Conservative management is generally preferred for empty nose syndrome. However, some patients continue to experience persistent symptoms. When symptoms do not resolve, surgical options are considered. Therefore, we reviewed the surgical and regenerative treatment options for empty nose syndrome. METHODS: PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar were searched from the earliest date provided in the database until December 2022. This review included studies that assessed treatment outcomes using patient symptom scores, including the Sino-Nasal Outcome Test (SNOT-20, -22, and -25) and the Empty Nose Syndrome 6-Item Questionnaire, supplemented by various clinical examinations. RESULTS: Twenty-eight studies were analyzed. Various materials were utilized, including submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants. The polyethylene implant was the most commonly used (23.3%), followed by autologous, homologous, or cadaveric costal cartilage (20%). The anterior-inferior lateral nasal wall was the most frequent site of administration. Most studies indicated that surgical intervention led to significant improvements in clinical outcomes, as evidenced by endoscopic exams, acoustic rhinometry, and computed tomography scans, along with patient-reported enhancements in nasal symptoms, psychological well-being, and overall health-related quality of life. However, several studies found no improvement in certain psychological-related questionnaires or saccharin transit times. The average follow-up duration was 12.0 months (range, 2.0-27.6 months). Only two studies reported postoperative adverse effects. CONCLUSION: Several surgical options and recent tissue regeneration techniques have demonstrated efficacy in treating empty nose syndrome. However, more detailed investigations involving a larger number of participants and a randomized control study are necessary to establish a standardized treatment protocol for patients with empty nose syndrome.

Influence of Gelatin on Adhesion, Proliferation, and Adipogenic Differentiation of Adipose Tissue-Derived Stem Cells Cultured on Soy Protein-Agarose Scaffolds.

Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein-agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering.

Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.

Impact of Aeroallergen Sensitization on Chronic Rhinosinusitis.

PURPOSE: This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization. METHODS: The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia. RESULTS: The allergic group exhibited higher total CT scores than the nonallergic group (P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores (P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores (P = 0.001 and 0.001, respectively). CONCLUSIONS: Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression.

RAG suppresses group 2 innate lymphoid cells.

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Further, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s.

Tissue specific stem cell therapy for airway regeneration.

Secondary atrophic rhinitis (AR), a consequence of mucosal damage during nasal surgeries, significantly impairs patient quality of life. The lack of effective, lasting treatments underscores the need for alternative therapeutic strategies. A major impediment in advancing research is the scarcity of studies focused on secondary AR. Our study addresses this gap by developing an animal model that closely mirrors the histopathological changes observed in patients with secondary AR. These changes include squamous metaplasia, goblet cell hyperplasia, submucosal fibrosis, and glandular atrophy. Upon administering human nasal turbinate stem cells embedded in collagen type I hydrogel in these models, we observed ciliary regeneration. This finding suggests the potential therapeutic benefit of this approach. Our animal models not only emulate the clinical manifestations of secondary AR but also serve as valuable tools for evaluating the efficacy of cell-based biotechnological interventions.

Administration of chromium picolinate and meloxicam alleviates regrouping stress in dairy heifers.

OBJECTIVE: This research investigated the effect of administering chromium (Cr) and meloxicam (MEL) on growth performance, cortisol and blood metabolite, and behaviors in young, regrouped heifers. METHODS: Fifty Holstein dairy heifers (body weight [BW] 198±32.7 kg and 6.5±0.82 months of age) were randomly assigned to non-regrouped group or four regrouped groups. Non-regrouped animals were held in the same pen throughout the entire experimental period (NL: non-regrouping and administration of lactose monohydrate [LM; placebo]). For regrouping groups, two or three heifers maintained in four different pens for 2 weeks were regrouped into a new pen and assigned to one of four groups: regrouping and LM administration (RL); regrouping and Cr administration (RC); regrouping and MEL administration (RM), and regrouping and Cr and MEL administration (RCM). LM (1 mg/kg BW), Cr (0.5 mg Cr picolinate/kg dry matter intake), and MEL (1 mg/kg BW) were orally administered immediately before regrouping. Blood was collected before regrouping (0 h) and at 3, 9, and 24 h and 7 and 14 d thereafter. Behaviors were recorded for 7 consecutive days after regrouping. RESULTS: Average daily gain was lower (p<0.05) in RL than NL heifers, but was higher (p<0.05) in RM, RC, and RCM than RL heifers. RL heifers had higher (p<0.05) cortisol than NL heifers on d 1 after regrouping. The cortisol concentrations in RC, RM, and RCM groups were lower (p<0.05) than in RL treatment 1 d after regrouping. Displacement behavior was greater (p<0.05) in RL group than all other groups at 2, 3, and 6 d after regrouping. CONCLUSION: Regrouping caused temporal stress, reduced growth performance, and increased displacement behavior in heifers. Administering Cr and MEL recovered the retarded growth rate and reduced displacement behavior, thereby alleviating regrouping stress.

Human Nasal Inferior Turbinate-Derived Neural Stem Cells Improve the Niche of Substantia Nigra Par Compacta in a Parkinson's Disease Model by Modulating Hippo Signaling.

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer's disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells. METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs. RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms. CONCLUSION: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.

Perinatal Risk Factors for Asthma and Allergic Rhinitis in Children and Adolescents.

OBJECTIVES: In this study, we evaluated the associations between birth-related exposures, postnatal factors, and the risk of allergic rhinitis and asthma in children and adolescents. METHODS: We performed a comprehensive search of five literature databases up to May 2023. To quantify the associations of birth-related exposures (birth weight, delivery mode, prematurity, sex, maternal age, and parental allergy history) and postnatal factors (birth order, number of siblings, breastfeeding exclusivity, and breastfeeding duration) with allergic disease, we calculated pooled odds ratios and 95% confidence intervals. We conducted subgroup analyses for allergic disease type, birth order, number of siblings, and parental allergy history. The methodological quality of the identified studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: This meta-analysis included 31 studies, encompassing 218,899 patients in total. The birth-related exposures of low birth weight, maternal age, and prematurity (less than 37 weeks gestation) were not significantly associated with the risk of asthma or allergic rhinitis during childhood or adolescence. Male sex, family history of allergy, and cesarean delivery were linked to an elevated risk of asthma or allergic rhinitis. Among postnatal factors, exclusive breastfeeding, breastfeeding for longer than 6 months, second or later birth order, and having siblings exhibited protective effects against allergic diseases in offspring. CONCLUSION: The risks of allergic rhinitis and asthma were elevated in male patients, those delivered by cesarean section, and those with a family history of allergy. Conversely, exclusive breastfeeding, breastfeeding for longer than 6 months, and having siblings corresponded to a reduced risk of respiratory allergic diseases.