Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

Effects of acupuncture at myofascial trigger points combined with sling exercise therapy on clinical recovery and cervical spine biomechanics in patients with cervical spondylotic radiculopathy.

OBJECTIVE: This research aimed to ascertain the effects of acupuncture at myofascial trigger points (MTrPs) in combination with sling exercise therapy (SET) on the clinical recovery and cervical spine biomechanics in patients with cervical spondylotic radiculopathy (CRS). METHODS: Eighty patients with CSR were divided into Group A and Group B. Group A was treated with acupuncture at MTrPs, and Group B was treated with acupuncture at MTrPs combined with SET. The cervical spine function, pain level, cervical spine biomechanics and the occurrence of complications were compared between the two groups before and after treatment. RESULTS: After treatment, the Japanese Orthopaedic Association scores, Clinical Assessment Scale for Cervical Spondylosis scores, cervical forward flexion angle, posterior extension angle, left lateral flexion angle, right lateral flexion angle, left lateral rotation angle, and right lateral rotation angle of the Group B were raised, and the Neck Disability index, Visual Analogue Scale scores, and Neck Pain Questionnaire scores were reduced versus those of the Group A. The difference in complication rates between the two groups was not of statistical significance. CONCLUSION: Acupuncture at MTrPs combined with SET promotes functional recovery of the cervical spine, reduces pain, and improves cervical spine biomechanics in patients with CRS.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.

Mn Single-Atom Nanozyme Functionalized 3D-Printed Bioceramic Scaffolds for Enhanced Antibacterial Activity and Bone Regeneration.

Infective bone defect is increasingly threatening human health. How to achieve the optimal antibacterial activity and regenerative repair of infective bone defect simultaneously is a huge challenge in clinic. Herein, this work reports a rational integration of Mn single-atom nanozyme into the 3D-printed bioceramic scaffolds (Mn/HSAE@BCP scaffolds). The integrated Mn/HSAE@BCP scaffolds can catalyze the conversion of H2 O2 to produce hydroxyl radical (• OH) and superoxide anion (O2 •- ) through cascade reaction. Besides, the prominent thermal conversion efficiency of Mn/HSAE@BCP scaffolds can be utilized for sonodynamic therapy (SDT). The synergetic strategy of chemodynamic therapy (CDT)/SDT enables the sufficient generation of reactive oxygen species (ROS) to kill Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Furthermore, the enhanced antibacterial efficacy of Mn/HSAE@BCP scaffolds is beneficial to upregulate the expression of osteogenesis-related markers (such as collagen 1(COL1), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteoprotegerin (OPG)) in vitro and further promote bone regeneration in vivo. The results demonstrate the good potential of Mn/HSAE@BCP scaffolds for the enhanced antibacterial activity and bone regeneration, which provide an effective method for the treatment of clinical infective bone defect.

Creation of Wood-Based Hierarchical Superstructures via In Situ Growth of ZIF-8 for Enhancing Mechanical Strength and Electromagnetic Shielding Performance.

Given the escalating prevalence of electromagnetic pollution, there is an urgent need for the development of high-performance electromagnetic interference (EMI) shielding materials. Herein, wood-based electromagnetic shielding materials have gained significant popularity due to their exceptional performance as building materials. In this study, a novel wood-based composite with electromagnetic shielding properties is developed. Through the in situ growth of zeolitic imidazolate framework-8 (ZIF-8) crystals on wood fibers, coupled with uniform integration of carbon nanotubes (CNTs), a multifunctional composite named ZIF-8/Poplar-CNT composite is synthesized via a one-step thermoforming process. The incorporation of CNTs endows the composites with excellent EMI shielding effectiveness (EMI SE). Among these elements, despite ZIF-8 crystals not possessing intrinsic electromagnetic shielding functionality, their distinctive dodecahedral structure proves adept at scattering and reflecting electromagnetic waves within the composites, further improving the electromagnetic shielding effect. Hence, the ZIF-8/Poplar-CNT composite (56.95 dB) has ≈10 dB higher EMI SE compared to that of the composites without ZIF-8 crystals. Meanwhile, ZIF-8 crystals endow the materials with excellent tensile strength (54.84 MPa, enhanced by 4 times). Moreover, the introduction of Zn2+ provides superior antibacterial properties. The potential applications of ZIF-8/Poplar-CNT composites extend to diverse areas such as building decoration, electronic products, and medical equipment.

Systemic delivery of proteins using novel peptides via the sublingual route.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

Prototype-Augmented Self-Supervised Generative Network for Generalized Zero-Shot Learning.

Generalized Zero-Shot Learning (GZSL) aims at recognizing images from both seen and unseen classes by constructing correspondences between visual images and semantic embedding. However, existing methods suffer from a strong bias problem, where unseen images in the target domain tend to be recognized as seen classes in the source domain. To address this issue, we propose a Prototype-augmented Self-supervised Generative Network by integrating self-supervised learning and prototype learning into a feature generating model for GZSL. The proposed model enjoys several advantages. First, we propose a Self-supervised Learning Module to exploit inter-domain relationships, where we introduce anchors as a bridge between seen and unseen categories. In the shared space, we pull the distribution of the target domain away from the source domain and obtain domain-aware features. To our best knowledge, this is the first work to introduce self-supervised learning into GZSL as learning guidance. Second, a Prototype Enhancing Module is proposed to utilize class prototypes to model reliable target domain distribution in finer granularity. In this module, a Prototype Alignment mechanism and a Prototype Dispersion mechanism are combined to guide the generation of better target class features with intra-class compactness and inter-class separability. Extensive experimental results on five standard benchmarks demonstrate that our model performs favorably against state-of-the-art GZSL methods.

The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv /Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc /ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc . Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis.

Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: • A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. • The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. • Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.

Cell-penetrating peptides for transmucosal delivery of proteins.

Enabling non-invasive delivery of proteins across the mucosal barriers promises improved patient compliance and therapeutic efficacies. Cell-penetrating peptides (CPPs) are emerging as a promising and versatile tool to enhance protein and peptide permeation across various mucosal barriers. This review examines the structural and physicochemical attributes of the nasal, buccal, sublingual, and oral mucosa that hamper macromolecular delivery. Recent development of CPPs for overcoming those mucosal barriers for protein delivery is summarized and analyzed. Perspectives regarding current challenges and future research directions towards improving non-invasive transmucosal delivery of macromolecules for ultimate clinical translation are discussed.

Integrated Bioinformatics Analysis Reveals Diagnostic Biomarkers and Immune Cell Infiltration Characteristics of Solar Lentigines.

Background: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers. Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features. Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs. Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells. Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.

3D hierarchic interfacial assembly of Au nanocage@Au along with IS-AgMNPs for simultaneous, ultrasensitive, reliable, and quantitative SERS detection of colorectal cancer related miRNAs.

Simultaneous, reliable, and ultra-sensitive analysis of promising miRNA biomarkers of colorectal cancer (CRC) in serum is critical for early diagnosis and prognosis of CRC. In this work, we proposed a novel 3D hierarchic assembly clusters-based SERS strategy with dual enrichment and enhancement designed for the ultrasensitive and quantitative analysis of two upregulated CRC-related miRNAs (miR-21 and miR-31). The biosensor contains the following: (1) SERS probe, Au nanocage@Au nanoparticles (AuNC@Au NPs) labeled with Raman reporters (RaRs). (2) magnetic capture unit, Ag-coated Fe3O4 magnetic nanoparticles (AgMNPs) modified with internal standard (IS). (3) signal amplify probes (SA probes) for the formation of hierarchic assembly clusters. Based on this sensing strategy, the intensity ratio IRaRs/IIS with Lg miRNAs presents a wide linear range (10 aM-100 pM) with a limit of detection of 3.46 aM for miR-21, 6.49 aM for miR-31, respectively. Moreover, the biosensor shows good specificity and anti-interference ability, and the reliability and repeatability of the strategy were then verified by practical detection of clinical serum. Finally, the biosensor can distinguish CRC cancer subjects from normal ones and guide the distinct tumor, lymph node, and metastasis (TNM) stages. Overall, benefiting from the face-to-face coupling of hierarchic assembly clusters, rapid magnetic enrichment and IS signal calibration of AgMNPs, the established biosensor achieves ultra-sensitive and simultaneous detection of dual miRNAs and opens potential avenues for prediction and staging of CRC.

Quantitative brain mapping using magnetic resonance fingerprinting on a 50-mT portable MRI scanner.

Ultralow-field magnetic resonance imaging (ULF-MRI) has broad application prospects because of its portable hardware system and low cost. However, the low B0 magnitude of ULF-MRI results in a reduced signal-to-noise ratio in qualitative images compared with that of commercial high-field MRI, which can affect the visibility and delineation of tissues and lesions. In this work, a magnetic resonance fingerprinting (MRF) approach is applied to a homemade 50-mT ULF-MRI scanner to achieve efficient quantitative brain imaging, which is an original and promising disease-diagnosis approach for portable MRI systems. An inversion recovery fast imaging with steady-state precession-based sequence is utilized for MRF through Cartesian acquisition. A microdictionary analysis method is proposed to select the optimal repetition time and flip angle variation schedule and ensure the best possible tissue discriminative ability of MRF. The T1 and T2 relaxation properties and the B1 + distribution are considered for estimation, and the results are compared with those of gold standard (GS) quantitative imaging or qualitative imaging methods. The phantom experiment indicates that the quantitative values obtained by schedule-optimized MRF show good agreement, and the bias from the GS results is acceptable. The in vivo experiment shows that the relaxation times of white and gray matter estimated by MRF are slightly lower than the reference data, and the relaxation times of lipid are within the range of the reference data. Compared with qualitative MRI under ULF, MRF can intuitively reflect various items of brain tissue information in a single scan, so it is a valuable addition to point-of-care imaging approaches.

8R-methoxy-9R-hydroxyl-fumitremorgin C, a new diketopiperazine alkaloid from Haima cold seep-derived fungus Aspergillus fumigatus CYH-5.

One novel diketopiperazine derivative 8R-methoxy-9R-hydroxyl-fumitremorgin C (1), together with twelve known compounds, was separated from the fungus Aspergillus fumigatus CYH-5 collected from Haima cold seep. The structures of the compounds were identified by NMR, MS, optical rotation, hydrolysis reaction and comparing with literatures. Among them, compounds 10 and 11 exhibited inhibitory effect against bacteria. Compound 11 showed inhibitory activity on α-glucosidase and compound 8 displayed acetylcholinesterase (AchE) inhibitory activity.

Revolutionizing the female reproductive system research using microfluidic chip platform.

Comprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes' manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere.

Bio-friendly long-term subcellular dynamic recording by self-supervised image enhancement microscopy.

Fluorescence microscopy has become an indispensable tool for revealing the dynamic regulation of cells and organelles. However, stochastic noise inherently restricts optical interrogation quality and exacerbates observation fidelity when balancing the joint demands of high frame rate, long-term recording and low phototoxicity. Here we propose DeepSeMi, a self-supervised-learning-based denoising framework capable of increasing signal-to-noise ratio by over 12 dB across various conditions. With the introduction of newly designed eccentric blind-spot convolution filters, DeepSeMi effectively denoises images with no loss of spatiotemporal resolution. In combination with confocal microscopy, DeepSeMi allows for recording organelle interactions in four colors at high frame rates across tens of thousands of frames, monitoring migrasomes and retractosomes over a half day, and imaging ultra-phototoxicity-sensitive Dictyostelium cells over thousands of frames. Through comprehensive validations across various samples and instruments, we prove DeepSeMi to be a versatile and biocompatible tool for breaking the shot-noise limit.

[Research on a portable shielding-free ultra-low field magnetic resonance imaging system].

The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.

All-analog photoelectronic chip for high-speed vision tasks.

Photonic computing enables faster and more energy-efficient processing of vision data1-5. However, experimental superiority of deployable systems remains a challenge because of complicated optical nonlinearities, considerable power consumption of analog-to-digital converters (ADCs) for downstream digital processing and vulnerability to noises and system errors1,6-8. Here we propose an all-analog chip combining electronic and light computing (ACCEL). It has a systemic energy efficiency of 74.8 peta-operations per second per watt and a computing speed of 4.6 peta-operations per second (more than 99% implemented by optics), corresponding to more than three and one order of magnitude higher than state-of-the-art computing processors, respectively. After applying diffractive optical computing as an optical encoder for feature extraction, the light-induced photocurrents are directly used for further calculation in an integrated analog computing chip without the requirement of analog-to-digital converters, leading to a low computing latency of 72 ns for each frame. With joint optimizations of optoelectronic computing and adaptive training, ACCEL achieves competitive classification accuracies of 85.5%, 82.0% and 92.6%, respectively, for Fashion-MNIST, 3-class ImageNet classification and time-lapse video recognition task experimentally, while showing superior system robustness in low-light conditions (0.14 fJ µm-2 each frame). ACCEL can be used across a broad range of applications such as wearable devices, autonomous driving and industrial inspections.

Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model.

BACKGROUND: The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. RESULTS: We found that, similar to that of FGF19WT, the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models. The therapeutic benefits of FGF19ΔKLB on cholestatic liver damage are attributable, according to the following mechanistic investigation, to the reduction of BA production, liver inflammation, and fibrosis. More importantly, FGF19ΔKLB did not induce any tumorigenesis effects during its prolonged treatment. CONCLUSIONS: Together, our findings raise hope that FGF19ΔKLB may represent a useful therapeutic strategy for the treatment of intrahepatic cholestasis.

The global/local (limited to some regions) effect of cesarean delivery on the risk of pediatric allergic rhinitis: a systematic review and meta-analysis.

Background: Allergic rhinitis is a chronic and refractory disease that can be affected by a variety of factors. Studies have shown an association between cesarean section and the risk of pediatric allergic rhinitis. Methods: The PubMed, Springer, Embase, Cochrane Library, and Web of Science databases were searched to retrieve all studies published from January 2000 to November 2022, focusing on the relationship between cesarean section and the risk of pediatric allergic rhinitis. A meta-analysis was conducted to find a correlation between cesarean section and the risk of pediatric allergic rhinitis. A subgroup analysis was performed, considering the region and family history of allergy, after adjusting for confounding factors. Pooled odds ratios (ORs) were calculated, publication bias was assessed using a funnel plot, and heterogeneity between study-specific relative risks was taken into account. Results: The results showed that cesarean section was significantly associated with an increased risk of pediatric allergic rhinitis (OR: 1.27, 95% CI: 1.20-1.35). Subgroup analysis stratified by region indicated that cesarean section increased the risk of pediatric allergic rhinitis, with the highest increase in South America (OR: 1.67, 95% CI: 1.10-2.52) and the lowest in Europe (OR: 1.13, 95% CI: 1.02-1.25). The results of the subgroup analysis stratified by family history of allergy indicate that family history of allergy was not associated with the risk of pediatric allergic rhinitis. Conclusion: An association exists between cesarean section as the mode of delivery and the increased risk of pediatric allergic rhinitis, and cesarean section is a risk factor for allergic rhinitis.