Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury.

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cells activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could impact nidogen-1 accessibility. Phosphoproteomics revealed that the 'AKI protector' Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin ß1 to induce Wnts in tubules to mitigate AKI. Altogether, our results support that fibroblast-selective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis.

Recent advances in c-Met-based dual inhibitors in the treatment of cancers.

The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.

Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Proteome characterization of liver-kidney comorbidity after microbial sepsis.

Sepsis is a life-threatening condition that occurs when the body responds to an infection but subsequently triggers widespread inflammation and impaired blood flow. These pathologic responses can rapidly cause multiple organ dysfunction or failure either one by one or simultaneously. The fundamental common mechanisms involved in sepsis-induced multiple organ dysfunction remain unclear. Here, employing quantitative global and phosphoproteomics, we examine the liver's temporal proteome and phosphoproteome changes after moderate sepsis induced by cecum ligation and puncture. In total, 4593 global proteins and 1186 phosphoproteins according to 3275 phosphosites were identified. To characterize the liver-kidney comorbidity after sepsis, we developed a mathematical model and performed cross-analyses of liver and kidney proteome data obtained from the same set of mice. Beyond immune response, we showed the commonly disturbed pathways and key regulators of the liver-kidney comorbidity are linked to energy metabolism and consumption. Our data provide open resources to understand the communication between the liver and kidney as they work to fight infection and maintain homeostasis.

Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis.

Brain metastasis of HER2+ breast cancer occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with Trastuzumab +/-HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in-vivo models for HER2+ BCBM has compromised the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis. We have generated and characterized new HER2+ BCBM cells (BCBM94) isolated from a patient HER2+ brain metastasis. Repeated hematogenic xenografting of BCBM94 consistently generated BCBM in mice. The clinically used receptor tyrosine kinase inhibitor (RTKi) Lapatinib blocked phosphorylation of all ErbB1-4 receptors and induced the intrinsic apoptosis pathway in BCBM94. Neuregulin-1 (NRG1), a ligand for ErbB3 and ErbB4 that is abundantly expressed in the brain, was able to rescue Lapatinib-induced apoptosis and clonogenic ability in BCBM94 and in HER2+ BT474. ErbB3 was essential to mediate the NRG1-induced survival pathway that involved PI3K-AKT signalling and the phosphorylation of BAD at serine 136 to prevent apoptosis. High throughput RTKi screening identified the brain penetrable Poziotinib as highly potent compound to reduce cell viability in HER2+ BCBM in the presence of NRG1. Successful in-vivo ablation of BCBM94- and BT474-derived HER2+ brain tumors was achieved upon two weeks of treatment with Poziotinib. MRI revealed BCBM remission upon poziotinib, but not with Lapatinib treatment. In conclusion, we have established a new patient-derived HER2+ BCBM in-vivo model and identified Poziotinib as highly efficacious RTKi with excellent brain penetrability that abrogated HER2+ BCBM brain tumors in our mouse models.

Construction of SnO2 buffer layer and analysis of its interface modification for Li and Li1.5Al0.5Ge1.5(PO4)3 in solid-state batteries.

SnO2 layer between Li1.5Al0.5Ge1.5(PO4)3 (LAGP) and lithium anode was prepared through simple scratch-coating process to improve interface properties. The physical phase, morphology, and electrochemical properties of Li/SnO2/LAGP structure were characterized by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and electrochemical analytical methods. It was found that SnO2 layer effectively improved the interface stability of LAGP and lithium anode. The prepared Li/SnO2/LAGP/SnO2/Li symmetric cell exhibited a large critical current density of 1.8 mA cm-2 and demonstrated excellent cycling characteristics. The polarization voltages of symmetric cell were 0.1 V and 0.8 V after 1000 h of cycling at current densities of 0.04 mA cm-2 and 0.5 mA cm-2, respectively. Li/SnO2@LAGP/LiFePO4 solid-state full cells were also assembled, exhibiting a discharge specific capacity of 150 mAh g-1 after 200 cycles at 0.1C with capacity retention rate of 96 %. The good interface properties of Li/SnO2/LAGP structure are attributed to the transformation of SnO2 layer into a buffer layer containing Li2O, Sn0, and LixSny alloy during cycling process, which effectively inhibits the reduction reaction between LAGP and lithium anode.

B cell-reactive triad of B cells, follicular helper and regulatory T cells at homeostasis.

Autoreactive B cells are silenced through receptor editing, clonal deletion and anergy induction. Additional autoreactive B cells are ignorant because of physical segregation from their cognate autoantigen. Unexpectedly, we find that follicular B cell-derived autoantigen, including cell surface molecules such as FcγRIIB, is a class of homeostatic autoantigen that can induce spontaneous germinal centers (GCs) and B cell-reactive autoantibodies in non-autoimmune animals with intact T and B cell repertoires. These B cell-reactive B cells form GCs in a manner dependent on spontaneous follicular helper T (TFH) cells, which preferentially recognize B cell-derived autoantigen, and in a manner constrained by spontaneous follicular regulatory T (TFR) cells, which also carry specificities for B cell-derived autoantigen. B cell-reactive GC cells are continuously generated and, following immunization or infection, become intermixed with foreign antigen-induced GCs. Production of plasma cells and antibodies derived from B cell-reactive GC cells are markedly enhanced by viral infection, potentially increasing the chance for autoimmunity. Consequently, immune homeostasis in healthy animals not only involves classical tolerance of silencing and ignoring autoreactive B cells but also entails a reactive equilibrium attained by a spontaneous B cell-reactive triad of B cells, TFH cells and TFR cells.

ZnSe/SnSe Heterostructure Incorporated with Selenium/Nitrogen Co-Doped Carbon Nanofiber Skeleton for Sodium-Ion Batteries.

Effective strategies toward building exquisite nanostructures with enhanced structural integrity and improved reaction kinetics will carry forward the practical application of alloy-based materials as anodes in batteries. Herein, a free-standing 3D carbon nanofiber (CNF) skeleton incorporated with heterostructured binary metal selenides (ZnSe/SnSe) nanoboxes is developed for Na-ion storage anodes, which can facilitate Na+ ion migration, improve structure integrity, and enhance the electrochemical reaction kinetics. During the carbonization and selenization process, selenium/nitrogen (Se/N) is co-doped into the 3D CNF skeleton, which can improve the conductivity and wettability of the CNF matrices. More importantly, the ZnSe/SnSe heterostructures and the Se/N co-doping CNFs can have a synergistic interfacial coupling effect and built-in electric field in the heterogeneous interfaces of ZnSe/SnSe hetero-boundaries as well as the interfaces between the CNF matrix and the selenide heterostructures, which can enable fast ion/electron transport and accelerate surface/internal reaction kinetics for Na-ion storage. The ZnSe/SnSe@Se,N-CNFs exhibit superior Na-ion storage performance than the comparative ZnSe/SnSe, ZnSe and SnSe powders, which deliver an excellent rate performance (882.0, 773.6, 695.7, 634.2, and 559.0 mAh g-1 at current rates of 0.1, 0.2, 0.5, 1, and 2 A g-1 ) and long-life cycling stability of 587.5 mAh g-1 for 3500 cycles at 2 A g-1 .

Effects of various wet environments on the characteristics of the dust cake deposited on the surface of filter media.

The effect of wet environments on the dust cake of filter media was studied. The collapse angles of dust particles and the collapse angles between dust particles and filter media increase with increasing dust moisture content, relative humidity, and spray rate. The smallest growth rate of collapse was observed under dust moisture content, while the largest growth rate occurred under the spray rate condition. The collapse angles between dust particles and filter media of coated filter media were smaller compared to those of mechanical filter media under different wet environments. The dust cake drag coefficients of both filter media initially increase and then decrease with an increase in the dust moisture content, decrease with the acceleration of the relative humidity, and show a pattern of first decreasing and then increasing as the spray rate increases. The dust loading capacity of both filter media follows an opposite trend to that of the dust cake drag coefficients.

Synthesis of Upper-Rim Sulfanylpropyl- and p-Methoxyphenylazo-Substituted Calix[4]arenes as Chromogenic Sensors for Hg2+ and Ag+ Ions.

A series of calix[4]arenes with upper-rim sulfanylpropyl and p-methoxyphenylazo groups (compounds 8-10) were synthesized and found to be effective chromogenic sensors for selectively detecting Hg2+, Hg+, and Ag+ ions among 18 screened metal perchlorates. In comparison to previously reported diallyl- and dithioacetoxypropyl-substituted calix[4]arenes (5, 6, 14, 15, and 16) and the newly synthesized compound 7, the distal (5,17)-disulfanylpropyl-substituted di-p-methoxyphenylazocalix[4]arene 9 demonstrated superior performance with a limit of detection of 0.028 µM for Hg2+ ions in a chloroform/methanol (v/v = 399/1) cosolvent. Job's plot revealed 1:1 binding stoichiometry for all these upper-rim sulfanylpropyl- and p-methoxyphenylazo-substituted calix[4]arenes 8-10 with Hg2+ ions, and Benesi-Hildebrand plots from ultraviolet/visible (UV-vis) titration spectra were used for the determination of their association constants. Our findings indicated that the distal orientation of two p-methoxyphenylazo and two sulfanylpropyl groups in calix[4]arenes 8-10 is more favorable for binding Hg2+ ions than the proximal (5,11-) orientation; moreover, the adjacent sulfanylpropyl groups exhibited superior coordination as ligands compared to the allyl and thioacetoxypropyl groups. Notably, compounds 8-10 displayed a comparable trend in their association with Ag+ ions, albeit with 1 order of magnitude lower binding constants and a distinct binding mode compared to Hg2+ ions. UV-vis spectroscopy, Job's plots, high-resolution mass spectrometry, and 1H nuclear magnetic resonance titration studies are presented and discussed.

How APTMS Acts as a Bridge to Enhance the Compatibility of the Interface between the Hydrophilic Poly(vinyl alcohol) Film and the Hydrophobic Stearic Acid Coating.

The hydrophobic modification of poly(vinyl alcohol) (PVA) film as a biodegradable packaging material has received significant attention in recent research. Despite the use of stearic acid (SA) as a coating for the PVA film, a challenge persists due to the poor compatibility between SA and PVA. This study addressed the aforementioned issue by utilizing (3-aminopropyl)trimethoxysilane (APTMS) as a bridging agent to establish a connection between the hydrophilic PVA film and the hydrophobic SA coating through hydrogen bonding and chemical reactions. First, SEM and EDS analyses confirmed the enhanced interfacial compatibility between the SA coating and the PVA film. Subsequently, the results from 1H NMR, FTIR, and XPS experiments presented evidence of hydrogen bonding and chemical reactions among APTMS, SA, and the PVA film. Interestingly, the PVA-APTMS-SA film demonstrated a contact angle of 120.77°, a water absorption of 7.81%, and a water vapor transmission rate of 8.69 g/m2/h. Furthermore, such a composite film displayed exceptional adhesion performance, requiring detachment stresses of 9.86 ± 0.91 and 6.17 ± 0.75 MPa when tested on glass and marble surfaces, respectively. In conclusion, the PVA-APTMS-SA film exhibited significant potential in extending the freshness of fresh-cut apples, making it a promising eco-friendly packaging material for food preservation.

Deciphering a global source of non-genetic heterogeneity in cancer cells.

Cell-to-cell variability within a clonal population, also known as non-genetic heterogeneity, has created significant challenges for intervening with diseases such as cancer. While non-genetic heterogeneity can arise from the variability in the expression of specific genes, it remains largely unclear whether and how clonal cells could be heterogeneous in the expression of the entire transcriptome. Here, we showed that gene transcriptional activity is globally modulated in individual cancer cells, leading to non-genetic heterogeneity in the global transcription rate. Such heterogeneity contributes to cell-to-cell variability in transcriptome size and displays both dynamic and static characteristics, with the global transcription rate temporally modulated in a cell-cycle-coupled manner and the time-averaged rate being distinct between cells and heritable across generations. Additional evidence indicated the role of ATP metabolism in this heterogeneity, and suggested its implication in intrinsic cancer drug tolerance. Collectively, our work shed light on the mode, mechanism, and implication of a global but often hidden source of non-genetic heterogeneity.

Dissecting and improving gene regulatory network inference using single-cell transcriptome data.

Single-cell transcriptome data has been widely used to reconstruct gene regulatory networks (GRNs) controlling critical biological processes such as development and differentiation. Although a growing list of algorithms has been developed to infer GRNs using such data, achieving an inference accuracy consistently higher than random guessing has remained challenging. To address this, it is essential to delineate how the accuracy of regulatory inference is limited. Here, we systematically characterized factors limiting the accuracy of inferred GRNs and demonstrated that using pre-mRNA information can help improve regulatory inference compared to the typically used information (i.e., mature mRNA). Using kinetic modeling and simulated single-cell data sets, we showed that target genes' mature mRNA levels often fail to accurately report upstream regulatory activities because of gene-level and network-level factors, which can be improved by using pre-mRNA levels. We tested this finding on public single-cell RNA-seq data sets using intronic reads as proxies of pre-mRNA levels and can indeed achieve a higher inference accuracy compared to using exonic reads (corresponding to mature mRNAs). Using experimental data sets, we further validated findings from the simulated data sets and identified factors such as transcription factor activity dynamics influencing the accuracy of pre-mRNA-based inference. This work delineates the fundamental limitations of gene regulatory inference and helps improve GRN inference using single-cell RNA-seq data.

Developing a Surgical Simulation Curriculum for the Rwandan Context.

OBJECTIVE: We report on the development and implementation of a surgical simulation curriculum for undergraduate medical students in rural Rwanda. DESIGN: This is a narrative report on the development of scenario and procedure-based content for a junior surgical clerkship simulation curriculum by an interdisciplinary team of simulation specialists, surgeons, anesthesiologists, medical educators, and medical students. SETTING: University of Global Health Equity, a new medical school located in Butaro, Rwanda. PARTICIPANTS: Participants in this study consist of simulation and surgical educators, surgeons, anesthesiologists, research fellows and University of Global Health Equity medical students enrolled in the junior surgery clerkship. RESULTS: The simulation training schedule was designed to begin with a 17-session simulation-intensive week, followed by 8 sessions spread over the 11-week clerkship. These sessions combined the use of high-fidelity mannequins with improvised, bench-top surgical simulators like the GlobalSurgBox, and low-cost gelatin-based models to effectively replace resource intensive options. CONCLUSIONS: Emphasis on contextualized content generation, low-cost application, and interdisciplinary design of simulation curricula for low-income settings is essential. The impact of this curriculum on students' knowledge and skill acquisition is being assessed in an ongoing fashion as a substrate for iterative improvement.

Development and validation of a diagnostic model for AFP-negative hepatocellular carcinoma.

PURPOSE: AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC). PATIENTS AND METHODS: The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation. RESULTS: Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892-0.938) in training set and 0.942(95% CI 0.921-0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883). CONCLUSIONS: Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC.

NFAT and NF-κB dynamically co-regulate TCR and CAR signaling responses in human T cells.

While it has been established that the responses of T cells to antigens are combinatorially regulated by multiple signaling pathways, it remains elusive what mechanisms cells utilize to quantitatively modulate T cell responses during pathway integration. Here, we show that two key pathways in T cell signaling, calcium/nuclear factor of activated T cells (NFAT) and protein kinase C (PKC)/nuclear factor κB (NF-κB), integrate through a dynamic and combinatorial strategy to fine-tune T cell response genes. At the cis-regulatory level, the two pathways integrate through co-binding of NFAT and NF-κB to immune response genes. Pathway integration is further regulated temporally, where T cell receptor (TCR) and chimeric antigen receptor (CAR) activation signals modulate the temporal relationships between the nuclear localization dynamics of NFAT and NF-κB. Such physical and temporal integrations together contribute to distinct modes of expression modulation for genes. Thus, the temporal relationships between regulators can be modulated to affect their co-targets during immune responses, underscoring the importance of dynamic combinatorial regulation in cellular signaling.

Long-Term Patient-Reported Symptom Improvement and Quality of Life after Transthoracic Diaphragm Plication in Adults.

BACKGROUND: Open and robotic-assisted transthoracic approaches for diaphragm plication are accepted surgical interventions for diaphragm paralysis and eventration. However, long-term patient-reported symptom improvement and quality of life (QOL) remains unclear. STUDY DESIGN: A telephone-based survey was developed focusing on postoperative symptom improvement and QOL. Patients who underwent open or robotic-assisted transthoracic diaphragm plication (2008-2020) across three institutions were invited to participate. Patients who responded and provided consent were surveyed. Likert responses on symptom severity were dichotomized and rates before and after surgery were compared using McNemar's test. RESULTS: Forty-one percent of patients participated (43 of 105 responded, mean age 61.0 years, 67.4% male, 37.2% robotic-assisted surgery), with an average time between surgery and survey of 4.1 ± 3.2 years. Patients reported significant improvement in dyspnea while lying flat (67.4% pre- vs 27.9% postoperative, p < 0.001), dyspnea at rest (55.8% pre- vs 11.6% postoperative, p < 0.001), dyspnea with activity (90.7% pre- vs 55.8% postoperative, p < 0.001), dyspnea while bending over (79.1% pre- vs 34.9% postoperative, p < 0.001), and fatigue (67.4% pre- vs 41.9% postoperative, p = 0.008). There was no statistical improvement in chronic cough. 86% of patients reported improved overall QOL, 79% had increased exercise capacity, and 86% would recommend surgery to a friend with a similar problem. Analysis comparing open and robotic-assisted approaches found no statistically significant differences in symptom improvement or QOL responses between the groups. CONCLUSIONS: Patients report significantly improved dyspneic and fatigue symptoms after transthoracic diaphragm plication, regardless of open or robotic-assisted approach. The majority of patients report improved QOL and exercise capacity.

GlobalSurgBox: A Portable Surgical Simulator for Surgical Trainees Worldwide.

OBJECTIVES: Identify barriers to surgical simulation in multiple countries across the income spectrum. Evaluate whether a novel, portable surgical simulator (GlobalSurgBox) would be valuable to surgical trainees and overcome these barriers. DESIGN: Trainees from high-, middle-, and low-income countries were instructed on how to perform surgical skills using the GlobalSurgBox. Participants were sent an anonymized survey after 1 week to evaluate practicality and helpfulness of the trainer. SETTING: Academic medical centers in 3 countries: USA, Kenya, and Rwanda. PARTICIPANTS: 48 medical students, 48 surgery residents, 3 medical officers, and 3 cardiothoracic surgery fellows. RESULTS: 99.0% of respondents agreed surgical simulation was an important aspect of surgical education. Despite 60.8% having access to simulation resources, only 3 of 40 (7.5%) US trainees, 2 of 12 (16.7%) of Kenyan trainees, and 1 of 10 (10.0%) Rwandan trainees used these resources routinely. 38 (95.0%) US trainees, 9 (75.0%) Kenyan trainees, and 8 (80.0%) Rwandan trainees with access to simulation resources stated there were barriers to using them. The frequently cited barriers included lack of convenient access and lack of time. After using the GlobalSurgBox, 5 (7.8%) US participants, 0 (0%) Kenyan participants, and 5 (38.5%) Rwandan participants reported lack of convenient access as a continued barrier to simulation. 52 (81.3%) US trainees, 24 (96.0%) Kenyan trainees, and 12 (92.3%) Rwandan trainees stated the GlobalSurgBox was a good facsimile of the operating room. 59 (92.2%) US trainees, 24 (96.0%) Kenyan trainees, and 13 (100%) Rwandan trainees stated the GlobalSurgBox better prepared them for clinical settings. CONCLUSIONS: A majority of trainees across all 3 countries reported multiple barriers to simulation in their current surgical training. The GlobalSurgBox eliminates many of these barriers by providing a portable, affordable, and realistic way to practice skills needed in the operating room.

Age-related seroprevalence trajectories of seasonal coronaviruses in children including neonates in Guangzhou, China.

OBJECTIVES: Four seasonal coronaviruses, including human coronavirus (HCoV)-229E and HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause approximately 15-30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period is still not well understood. METHODS: We evaluated the serological responses against the four seasonal coronaviruses in 1886 children aged under 18 years by using enzyme-linked immunosorbent assay. The optical density values against each HCoV were determined from each sample. Generalized additive models were constructed to determine the relationship between age and seroprevalence throughout the whole childhood period. The specific antibody levels against the four seasonal coronaviruses were also tested from the plasma samples of 485 pairs of postpartum women and their newborn babies. RESULTS: The immunoglobulin (Ig) G levels of the four seasonal coronaviruses in the mother and the newborn babies were highly correlated (229E: r = 0.63; OC43: r = 0.65; NL63: r = 0.69; HKU1: r = 0.63). The seroprevalences in children showed a similar trajectory in that the levels of IgG in the neonates dropped significantly and reached the lowest level after the age of around 1 year (229E: 1.18 years; OC43: 0.97 years; NL63: 1.01 years; HKU1: 1.02 years) and then resurgence in the children who aged older than 1 year. Using the lowest level from the generalized additive models as our cutoff, the seroprevalences for HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were 98.11%, 96.23%, 96.23% and 94.34% at the age of 16-18 years. CONCLUSION: Mothers share HCoV-specific IgGs with their newborn babies and the level of maternal IgGs waned at around 1 year after birth. The resurgence of the HCoV-specific IgGs was found thereafter with the increase in age suggesting repeated infection occurred in children.