Nasal Mucosal Cytokines as Potential Biomarkers for Assessing Disease Severity and Class of Pathogen in Children with Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in children. Assessing disease severity and etiology remains challenging in the clinical setting. The objective of this study was to identify mucosal biomarkers that could potentially assist with patient classification. METHODS: We analyzed mucosal concentrations of cytokines in nasopharyngeal samples obtained from a convenience sample of 182 children with CAP and 26 matched healthy controls. Pathogens were identified by cultures and molecular assays. Severe disease was defined by hospital stay ≥ 3 days, and/or PICU admission. Data were analyzed according to identified pathogens and disease severity. RESULTS: Children with CAP and detected atypical bacteria had significantly higher concentrations of MCP-2, IFN-γ and CXCL10 among others compared with those with typical bacteria. Children with influenza virus had significantly higher concentrations of MCP-2, CXCL10, CXCL11, CX3CL1, and IFN-γ than those with typical bacteria. Additionally, children with severe CAP had significantly higher concentrations of CCL23 than children with mild/moderate disease, irrespective of the pathogen(s) identified. CONCLUSIONS: We identified differences in mucosal concentrations of inflammatory and antiviral cytokines in children with CAP according to disease severity and detected pathogens. Mucosal biomarkers represent a promising approach to help assessing disease severity and etiology.

Molecular Structures of Poly(methyl methacrylate) at Different Buried Interfaces Revealed by Sum Frequency Generation Vibrational Spectroscopy.

Silica or calcium fluoride (CaF2) substrate-supported poly(methyl methacrylate) (PMMA) thin films as insulating layers are commonly used in photoelectric/photovoltaic devices to improve the efficiency or stability of these devices. However, a comparative investigation of molecular structures at buried PMMA/silica and PMMA/CaF2 interfaces under thermal stimuli remains unexplored. In this study, we qualitatively and quantitatively revealed different molecular orderings and orientations of PMMA at two interfaces before and after annealing using sum frequency generation (SFG) vibrational spectroscopy. SFG vibrations were carefully assigned by using various deuterated PMMAs. SFG results indicated that, at the buried PMMA/silica interface, the side OCH3 groups were prone to lie down before annealing and tended to stand up after annealing. In contrast, the case was the opposite at the buried PMMA/CaF2 interface. The relative hydrophobicity/hydrophilicity of the two substrates and the developed hydrogen bonds upon annealing at the buried PMMA/silica interface, which is absent at the CaF2 surface, are believed to be the driving forces for different interfacial molecular structures. This study benefits the molecular-level understanding of the interfacial local structural relaxation of polymers at buried interfaces and the rational design of photoelectric/photovoltaic devices from the molecular level.

The transcription factor ZNF248 promotes colorectal cancer metastasis by binding to ZEB1.

Colorectal cancer (CRC) is one of the most common malignant tumors globally, with metastasis emerging as the leading cause of mortality in CRC patients. Transcription factors play pivotal roles in the metastatic process. Using bioinformatics tools, we analyzed the TCGA-COAD and GES146587 datasets and identified ZNF248 participating in tumor progression. By analyzing 100 CRC patient tissues, it is found that ZNF248 is highly expressed in cancer tissue as well as in CRC cell lines identified by qRT-PCR. Our study discovered that ZNF248 enhances CRC cell migratory and invasive capabilities. A positive correlation was found between ZNF248 and epithelial-mesenchymal transition (EMT)-related markers (ZEB1, snail1), while E-cadherin exhibited a negative correlation with ZNF248. In addition, the analysis of the TCGA dataset demonstrated a strong correlation between the mRNA level of ZNF248 and ZEB1 expressions. Furthermore, it is found that the overexpression of ZEB1 could reverse CRC cell invasion and migration, along with the inhibition on EMT marker expressions induced by the RNA interference with ZNF248. Immunohistochemical analysis indicated a substantial association of ZNF248 expression with the lymph node metastasis, and with the liver metastasis (P =0.01, P =0.01), and a positive correlation between ZNF248 and ZEB1 expression (P =0.021) was also identified. Using Chip-PCR assay, it is found that ZNF248 bound to the ZEB1 promoter region. These findings showed that ZNF248 promotes CRC metastasis in vivo, revealed its role as an oncogene in CRC by targeting ZEB1 and activating the EMT pathway, which provided novel and promising biomarkers for CRC therapy through targeting ZEB1.

Downscaling soil moisture in regions with high soil heterogeneity: the solution based on ensemble learning with sequential and parallel learner.

Soil moisture plays an important role in the water and heat exchanges between the land surface and atmosphere, and it has great importance for agricultural production, ecological planning, and water resources management. Although microwave remote sensing has been widely used in large-scale soil moisture monitoring, the accuracy of the downscaled retrieval results cannot be guaranteed for regions with high vegetation coverage and high soil heterogeneity. To address these challenges, this study built soil moisture indice set based on MODIS and elevation data by calculating the Pearson correlation coefficient (R) and Maximum Information Coefficient (MIC), then constructed decision tree models (Gradient Boosting Decision Tree and Random Forest) about the indice set and low-resolution Soil Moisture Active Passive (SMAP) by using two ensemble learning methods (Bagging and Boosting). The models were applied to the high-resolution soil moisture indices in Jilin Province for the years 2017 to 2020 to generate 1 km-resolution products. In the validation process, Triple Collocation Analysis (TCA), comparison of soil moisture maps with coarse and fine resolution, and in-situ measurements in Lishu County, Tongyu County, and Jilin City were used to evaluate the differences between downscaling soil moisture results and ground observations at network, seasonal and point scales. The results were as follows: (1) The correlation coefficient (R2) calculated by the TCA method was 0.733 (GBDT_36km) > 0.649 (RF_36km), and the error variance was 0.0004 (GBDT_36km) < 0.00058 (RF_36km). (2) R at network scale was 0.798 (GBDT_SM) > 0.662 (RF_SM), RMSE was 0.040 (GBDT_SM) < 0.044 (RF_SM), the point scale R was 0.864 (GBDT_SM) > 0.833 (RF_SM), RMSE was 0.029 (GBDT_SM) < 0.039 (RF_SM). The R in four stages of the growth period was GBDT_SM > RF_SM, RMSE was GBDT_SM < RF_SM. In conclusion, the GBDT and RF models can reliably downscale soil moisture in Jilin Province, and the Boosting ensemble learning method represented by GBDT had a better estimation performance.

Sex difference in alcohol consumption associated with colorectal cancer risk in Quzhou, China: A nested case-control study.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.

Research trends between intestinal microbiome and colorectal cancer: A bibliometric analysis.

This was the first bibliometric analysis between intestinal microbiome and colorectal cancer, analyzing the current status and future trends. The annual publication output would be constantly increasing in the future. Future research hotspots would focus on the new drugs development, pathogenesis research and targeted therapy.

Effects of Lake Erie dredged material on microbiomes in a farm soil of northwestern Ohio.

Dredged materials are often considered as candidates for replenishing lost topsoils in the watersheds of rivers and lakes. This study aimed to investigate the impacts of Lake Erie dredged material on the microbial community in a farm soil of northwestern Ohio. Dredged material from the Toledo Harbor, OH was mixed with a local farm soil at ratios of 0:100, 10:90, 20:80, and 100:0 for soybean growth in a greenhouse for 123 days and was subject to 16S rRNA gene sequencing. α-Diversity analysis revealed that although the original dredged material hosted a highly diverse microbiome, soils blended with the dredged material had similar levels of bacterial diversity to 100% farm soil throughout the experiment. ß-Diversity analysis demonstrated that, given the same plant status, that is, with or without soybean, blended soils had similar bacterial communities to 100% farm soil during the experiment. Furthermore, by the end of the experiment, all soils with soybeans merged into one cluster distinctive from those without the plants, indicating that the growth of plants played a dominating role in defining the structure of soil microbiomes. The majority (73.8%) of the operational taxonomy units that were unique to the original dredged material were not detected by the end of the experiment. This study demonstrates that up to 20% of the dredged material can be safely blended into the farm soil without distorting the microbial communities of the latter, implying a potential beneficial use of the dredged material for topsoil restoration.

The Efficacy of Machine Learning Models for Predicting the Prognosis of Heart Failure: A Systematic Review and Meta-Analysis.

INTRODUCTION: Heart failure (HF) is a major global public health concern. The application of machine learning (ML) to identify individuals at high risk and enable early intervention is a promising approach for improving HF prognosis. We aim to systematically evaluate the performance and value of ML models for predicting HF prognosis. METHODS: PubMed, Web of Science, Scopus, and Embase online databases were searched up to April 30, 2023, to identify studies on the use of ML models to predict HF prognosis. HF prognosis primarily encompasses readmission and mortality. The meta-analysis was conducted by MedCalc software. Subgroup analyses include grouping based on types of ML models, time intervals, sample sizes, the number of predictive variables, validation methods, whether to conduct hyperparameter optimization and calibration, data set partitioning methods. RESULTS: A total of 31 studies were included. The most common ML models were random forest, boosting, support vector machine, neural network. The area under the receiver operating characteristic curve (AUC) for predicting HF readmission was 0.675 (95% CI: 0.651-0.699, p < 0.001), and the AUC for predicting HF mortality was 0.790 (95% CI: 0.765-0.816, p < 0.001). Subgroup analyses revealed that models with the prediction time interval of 1 year, sample sizes ≥10,000, the number of predictive variables ≥100, external validation, hyperparameter tuning, calibration adjustment, and data set partitioning using 10-fold cross-validation exhibited favorable performance within their respective subgroups. CONCLUSION: The performance of ML models in predicting HF readmission is relatively poor, while its performance in predicting HF mortality is moderate. The quality of the relevant studies is generally low, it is essential to enhance the predictive capabilities of ML models through targeted improvements in practical applications.

Heart failure potentially affects the cortical structure of the brain.

BACKGROUND: Heart failure (HF) has been reported to affect cerebral cortex structure, but the underlying cause has not been determined. This study used Mendelian randomization (MR) to reveal the causal relationship between HF and structural changes in the cerebral cortex. METHODS: HF was defined as the exposure variable, and cerebral cortex structure was defined as the outcome variable. Inverse-variance weighted (IVW), MR-Egger regression and weighted median (WME) were performed for MR analysis; MR-PRESSO and Egger's intercept was used to test horizontal pleiotropy; and "leave-one-out" was used for sensitivity analysis. RESULTS: Fifty-two single nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs), and there was no horizontal pleiotropy in the IVs. According to the IVW analysis, the OR and 95% CI of cerebral cortex thickness were 0.9932 (0.9868-1.00) (P=0.0402), and the MR-Egger intercept was -15.6× 10-5 (P = 0.7974) and the Global test pval was 0.078. The P-value of the cerebral cortex surface was 0.2205, and the MR-Egger intercept was -34.69052 (P= 0.6984) and the Global Test pval was 0.045. HF had a causal effect on the surface area of the caudal middle frontal lobule (P=0.009), insula lobule (P=0.01), precuneus lobule (P=0.049) and superior parietal lobule (P=0.044). CONCLUSIONS: HF was potentially associated with changes in cortical thickness and in the surface area of the caudal middle frontal lobule, insula lobule, precuneus lobule and superior parietal lobule.

A unicentric center, multicenter, and mixed-type Castleman disease: Three case reports and a review of the literature.

RATIONALE: Due to the lack of specificity symptoms and site of onset of castleman disease (CD), it is difficult to diagnose and poses unique challenges for both patients and clinicians, leading to confusion in diagnosis and delays in treatment. To enhance understanding, we present 3 cases of CD treated at our hospital, including a single-center, multicenter, and mixed-type CD. PATIENT CONCERNS: Case 1: A 53-year-old female patient was admitted with a chief complaint of "abdominal pain and fever for 10 days." Marked enlargement of inguinal lymph nodes on both sides was observed. Case 2: A 58-year-old female patient was admitted with the main complaint of "discovering a left lower abdominal mass during a routine checkup for the past 10 days." Upon deep palpation, a palpable mass of approximately 5.0 * 3.0 cm was identified in the left lower abdomen. Case 3: A 40-year-old male patient was admitted with the main complaint of "progressive right upper abdominal and lumbar back pain for over 6 months." Computed tomography examination revealed multiple nodular soft tissue masses between the abdominal aorta and inferior vena cava, with the largest measuring 5.0 * 4.0 cm. DIAGNOSES: Based on the immunohistochemical results, the diagnoses for the 3 patients are as follows: Case 1: Multicentric Castleman's Disease (Mixed Type). Case 2: Pelvic Retroperitoneal Castleman Disease (Hyaline Vascular Type). Case 3: Castleman Disease Multicentric Type. INTERVENTION: Case 1: cyclophosphamide 0.6-1 g + vincristine 2 mg + methylprednisolone 50 mg/5 days. Cyclophosphamide 1 g + prednisone 30-50 mg/5 days. This alternating chemotherapy cycle is repeated every 6 months. Case 2: Laparoscopic pelvic mass excision surgery. Case 3: Surgical excision of the mass. OUTCOMES: Case 1: After a 43-month follow-up, the patient's general symptoms have improved compared to before, but regular chemotherapy is still necessary at present. Case 2: The patient did not take any medication postoperatively, and there has been no evidence of metastasis or recurrence during the 18-month follow-up. Case 3: The patient did not take any medication, and there has been no evidence of metastasis or recurrence during the 21-month follow-up. LESSONS SUBSECTIONS: The lack of specific signs on imaging studies and nonspecific blood tests increases the difficulty of diagnosis. However, tissue biopsy remains a feasible option. Therefore, we recommend conducting thorough examinations for suspected CD patients to reduce misdiagnosis and determine the CD type for effective targeted treatment.

Probing Interfacial Aging of Model Adhesion Joints under a Hygrothermal Environment at a Molecular Level.

Generally, for adhesive joints, the polar water molecules in humid environments can have a critical effect on the interfacial structures and structural evolution adjacent to the solid substrates. Regarding this, it is still a big challenge to detect and understand the interfacial hygrothermal aging process at the molecular level in real time and in situ. In this study, to trace the interfacial hygrothermal aging process of a classical epoxy formula containing diglycidyl ether of biphenyl A (DGEBA) and 2,2'-(ethylenedioxy) diethylamine (EDDA) with sapphire and fused silica in a typical hygrothermal environment (85 °C and 85% RH), sum frequency generation (SFG) vibrational spectroscopy was used to probe the molecular-level interfacial structural change over the time. The structural evolution dynamics at the buried epoxy/sapphire and epoxy/silica interfaces upon hygrothermal aging were revealed directly in situ. The interfacial delamination during hygrothermal aging was also elucidated from the molecular level. Upon hygrothermal aging, the interfacial CH signals, such as the ones from methyl, methylene, and phenyl groups, decreased significantly and the water OH signals increased substantially, indicating the water molecules had diffused into the interfaces and destroyed the original interactions between the epoxy formula and the substrates. Further analysis indicates that when the integrated signals in the CH range declined to their minimum and leveled off, the interfacial delamination happened. The tensile experiment proved the validity of these spectroscopic experimental results. Our study provides first-hand and molecular-level evidence on a direct correlation between the diffusion of the surrounding water molecules into the interface and the evolution/destruction of the interfacial structures during hygrothermal aging. More importantly, it is proved, SFG can be developed into a powerful tool to noninvasively reveal the local interfacial delamination in real time and in situ under extreme hygrothermal conditions, complemented by the mechanic test.

Qifu Yixin Formula Improves Heart Failure by Enhancing ß-Arrestin2 Mediated the SUMOylation of SERCA2a.

Purpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting ß-arrestin2 (ß-arr2)-mediated SERCA2a SUMOylation. Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. ß-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. ß-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to ß-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein. Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted ß-arr2 expression, whereas Barbadin (ß-arr2 inhibitor) or ß-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with ß-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein. Conclusion: QFYXF improves HF by promoting ß-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.

Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes.

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.

Regulation of saturation magnetization of magnetite by doping with group III elements.

Magnetic Fe3O4 nanoparticles show promising applications in nanomedicine. However, the saturation magnetization (MS) of Fe3O4 nanoparticles synthesized in laboratory is usually not high enough, which greatly limits their application in drug delivery and magnetic hyperthermia. Here, by accurate hybrid density functional computation, the doping behavior of group III elements (including Al, Ga, and In) and the effects on magnetic and electronic properties are well studied. The results show that the doping behavior depends on the concentration of dopants. Interestingly, appropriate Ga and In doping concentrations can significantly increase the MS of Fe3O4. In addition, the doping of group III elements (Al, Ga and In) into Fe3O4 would not induce any defect states in the band gap but slightly increases the band gap. Our results provide a simple and feasible scheme for increasing the MS of magnetite, which is significant for the applications of Fe3O4 nanoparticles in drug delivery and magnetic hyperthermia.

Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations.

Infants necessitate vaccinations to prevent life-threatening infections. Our understanding of the infant immune responses to routine vaccines remains limited. We analyzed two cohorts of 2-month-old infants before vaccination, one week, and one-month post-vaccination. We report remarkable heterogeneity but limited antibody responses to the different antigens. Whole-blood transcriptome analysis in an initial cohort showed marked overexpression of interferon-stimulated genes (ISGs) and to a lesser extent of inflammation-genes at day 7, which normalized one month post-vaccination. Single-cell RNA sequencing in peripheral blood mononuclear cells from a second cohort identified at baseline a predominantly naive immune landscape including ISGhi cells. On day 7, increased expression of interferon-, inflammation-, and cytotoxicity-related genes were observed in most immune cells, that reverted one month post-vaccination, when a CD8+ ISGhi and cytotoxic cluster and B cells expanded. Antibody responses were associated with baseline frequencies of plasma cells, B-cells, and monocytes, and induction of ISGs at day 7.

Efficacy of prophylactic negative pressure wound therapy after open ventral hernia repair: a systematic review meta-analysis.

INTRODUCTION: The susceptibility to surgical site occurrence (SSO) is high following ventral hernia repair (VHR) surgery. SSO severely increases the physical and mental burden on patients. The main purpose of this review was to analyze the efficacy of negative pressure wound therapy (NPWT) after open VHR(OVHR) and explore benefits to patients. METHODS: The Cochrane Library, PubMed, and Embase databases were searched from the date of establishment to 15 October 2022. All randomized controlled trials and retrospective cohort studies comparing NPWT with standard dressings after OVHR were included. The Revman 5.4 software recommended by Cochrane and the STATA16 software were used in this meta-analysis. RESULTS: Fifteen studies (involving 1666 patients) were identified and included in the meta-analysis, with 821 patients receiving NPWT. Overall, the incidence rate of SSO in the NPWT group was lower compared to the control group (odds ratio [OR] = 0.44; 95% confidence interval [CI] = 0.21-0.93; I2 = 86%; P = 0.03). The occurrence rate of surgical site infection (SSI; OR = 0.51; 95% CI = 0.38-0.68, P < 0.001), wound dehiscence (OR = 0.64; 95% CI = 0. 43-0.96; P = 0.03), and hernia recurrence (OR = 0.51; 95% CI = 0.28-0.91, P = 0.02) was also lowered. There was no significant difference in seroma (OR = 0.76; 95% CI = 0.54-1.06; P = 0.11), hematoma (OR = 0.53; 95% CI = 0.25-1.11; P = 0.09), or skin necrosis (OR = 0.83; 95% CI = 0.47-1.46; P = 0.52). CONCLUSION: NPWT can effectively decrease the occurrence of SSO, SSI wound dehiscence and hernia recurrence and should be considered following OVHR.

Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age. One Sentence Summary: Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.