Epilepsy and thyroid cancer are prevalent disorders with distinct etiologies; however, emerging evidence suggests the presence of shared molecular mechanisms that remain largely unexplored. In this study, we aimed to identify and characterize common hub genes and potential diagnostic markers linking these two conditions using comprehensive in silico and in vitro approaches. Differentially expressed genes (DEGs) were analyzed from epilepsy datasets (GSE44456, GSE186334) and thyroid cancer datasets (GSE60542, GSE153659), leading to the identification of four shared hub genes: CD44, CALCOCO2, ALDH4A1, and CLEC16A. Expression validation using RT-qPCR confirmed consistent patterns, with CD44 and CLEC16A significantly upregulated and CALCOCO2 and ALDH4A1 downregulated in disease cell lines compared to controls. Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic potential for these genes in both diseases, with area under the curve (AUC) values exceeding 0.90. Functional enrichment and pathway analyses revealed that these genes are involved in oncogenic signaling, immune regulation, and tumor progression. Genetic alteration analysis indicated frequent mutations and copy number variations, while promoter methylation profiling suggested epigenetic regulation associated with disease outcomes. Survival analysis further identified ALDH4A1 and CLEC16A as prognostic markers. Moreover, in vitro and in vivo experiments demonstrated that CD44 and CLEC16A regulate cellular proliferation, migration, and clonogenicity through extracellular matrix (ECM)-receptor interactions involving CCL5, STAT3, CXCR4, and RAC1 signaling pathways. Collectively, these findings provide new insights into the shared molecular landscape of epilepsy and thyroid cancer, highlighting potential diagnostic biomarkers and therapeutic targets.

Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the cell lines was compiled from the ATCC, Catalogue of Somatic Mutations in Cancer (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, and Depmap portal databases.

Following the publication of the above article and a corrigendum (doi: 10.3892/or.2017.5455) that was issued in 2017 to address issues of incorrect data assembly in Figs. 3 and  7, an interested reader drew to our attention that data also appeared to be duplicated in Fig. 4C, and data featured in Figs. 2 and 5 subsequently appeared in an article published by the same research group in the journal Oncotarget. Additionally, following an independent re‑evaluation of the data in this paper made by the Editorial Office, duplicated data were also noted in Fig. 5A, and some of the data in question subsequently appeared in an article in Journal of Enzyme Inhibition and Medicinal Chemistry in 2022 written by different authors at different institutes, which has since been retracted. In view of these additional findings, even though the possibility of a further corrigendum was originally considered, the Editor of Oncology Reports has decided that the paper should be retracted on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readrship for any inconvenience caused. [Oncology Reports 32: 205‑212, 2014; DOI: 10.3892/or.2014.3201].

Lung cancer is one of the most common malignancies worldwide, and the prognosis remains unsatisfactory with conventional treatments. Our research revealed that miR-100 is significantly decreased in non-small cell lung cancer (NSCLC) tissues and cell lines, indicating its potential role in NSCLC development. The upregulation of miR-100 expression inhibited the growth of L18 NSCLC cells, while its downregulation increased the growth of A549 NSCLC cells. Cell cycle dysregulation is a key factor in NSCLC development. CDC25A is a vital cell cycle regulator that promotes cell cycle progression. Our objective was to determine the function of the CDC25A protein and its effect on the prognosis of NSCLC patients. The luciferase reporter gene assay demonstrated direct targeting of the 3' non-coding sequence of CDC25A by miR-100-3p. Western blot analysis confirmed that the protein expression levels of cyclin D1, CDK6, pRb, and E2F3 decreased upon miR-100 overexpression. Furthermore, cell cycle analysis demonstrated that miR-100 overexpression led to G1 phase arrest and a concomitant reduction in S phase entry in NSCLC cells. In vivo studies using a xenograft mouse model demonstrated that miR-100 overexpression inhibited tumor growth, while its inhibition accelerated it. Rescue experiments confirmed that CDC25A partially reversed the cell cycle arrest and growth suppression mediated by miR-100. This study's findings suggest that miR-100 can inhibit NSCLC progression by specifically targeting CDC25A, a cell cycle regulator, and its downstream molecular targets. Hence, miR-100 may have significant therapeutic potential against NSCLC.

Mesenchymal stem cells (MSCs), suffering from diverse gene hits, undergo malignant transformation and aberrant osteochondral differentiation. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a nonreceptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear. Here, we showed that MSCs bearing the activating SHP2 E76K mutation underwent malignant transformation into sarcoma stem -like cells. We revealed that the SHP2 E76K mutation in mouse MSCs led to hyperactive mitochondrial metabolism by activating mitochondrial complexes I and III. Inhibition of complexes I and III prevented hyperactive mitochondrial metabolism and malignant transformation of SHP2 E76K MSCs. Mechanistically, we verified that SHP2 underwent liquid -liquid phase separation (LLPS) in SHP2 E76K MSCs. SHP2 LLPS led to its dissociation from complexes I and III, causing their hyperactivation. Blockade of SHP2 LLPS by LLPS-defective mutations or allosteric inhibitors suppressed complex I and III hyperactivation as well as malignant transformation of SHP2 E76K MSCs. These findings reveal that complex I and III hyperactivation driven by SHP2 LLPS promotes malignant transformation of SHP2 E76K MSCs and suggest that inhibition of SHP2 LLPS could be a potential therapeutic target for the treatment of activated SHP2-associated cancers.

Sunitinib based adjuvant chemotherapy combined with chloroquine (CQ) for the treatment of renal cell carcinoma (RCC) is in clinical trials; however, its anti-RCC effect and the mechanism remain unclear. In the present study, the anti-RCC effect of sunitinib with CQ and the underlying mechanism was investigated. An MTT assay demonstrated that CQ enhanced the proliferation inhibitory effect of sunitinib against the OS-RC-2 RCC cell line. CQ inhibited sunitinib-induced autophagy in OS-RC-2, which was evidenced by the inhibition of autophagic vacuoles, acidic vesicular organelle formation, light chain 3 (LC3)-II recruitment to the autophagosomes and the conversion of LC3-I to LC3-II, as induced by sunitinib. The inhibition of autophagy by CQ enhanced sunitinib-induced apoptosis, which was characterized by the activation of caspase-3, caspase-9, Bcl-2 and p53. Additionally, the exposure of OS-RC-2 cells to CQ and sunitinib resulted in the inhibition of AKT, tuberous sclerosis complex 2, mechanistic target of rapamycin and p70 ribosomal S6 kinase, which are associated with cell proliferation. In in vivo study, a combination of sunitinib with CQ in mice significantly reduced OS-RC-2 cell xenograft growth compared with the sunitinib alone group. In conclusion, the present study demonstrated that CQ may enhance the anti-RCC effect of sunitinib by inhibiting the autophagy induced by sunitinib, and enhance the rate of apoptosis. Inhibiting cell proliferation may also serve a role in the synergistic antitumor effect of sunitinib and CQ. These data suggest that combination therapy of sunitinib with CQ may be a promising strategy for adjuvant chemotherapy in RCC.

Gastric cancer (GC) remains a significant global health challenge due to its high morbidity and mortality rates. The development of GC is a multi-hit process and the exploration of precancerous lesions is crucial. To elucidate the molecular and cellular dynamics underlying gastric carcinogenesis, we conducted an integrative single-cell RNA sequencing analysis of 26,028 high-quality cells from gastric antral mucosa biopsies across various stages, including non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, and early gastric cancer. By constructing a detailed single-cell atlas, we identified distinct epithelial cell subpopulations and their corresponding molecular signatures. We focused on the biological link between gastric epithelial cells and cancer cells. Notably, we observed that gland mucous cells acquired an intestinal-like stem cell phenotype during metaplasia, with MUC6, MUC2 and OLFM4 emerging as the specific markers for unique endocrine cells in early malignant lesions. Additionally, our analysis highlighted UPP1 as a key oncogene, with its expression progressively increasing from normal epithelial cells to malignant cells. UPP1 upregulation was shown to promote GC cell proliferation and migration, implicating it in the oncogenic process. Further, we explored the impact of Helicobacter pylori infection on gene expression, revealing that Helicobacter pylori infection upregulates UPP1 via the NF-κB pathway. Our cell-cell communication analysis underscored the significant role of the Macrophage migration inhibitory factor pathway in the tumor microenvironment, contributing to GC progression. Various key molecules involved in intestinal metaplasia, along with UPP1 and the Macrophage migration inhibitory factor pathway, collectively illustrate the multifaceted nature and complexity of gastric cancer evolution, highlighting the cumulative impacts that drive tumorigenesis.

OBJECTIVES:Heterotopic ossification (HO), whether hereditary or traumatic, refers to the abnormal formation of bone in extraskeletal sites, often triggered by inflammation or flare-ups. Unfortunately, there are currently no effective treatments for HO. Metformin is well-known for its anti-diabetic, anti-inflammatory, anti-aging, and anti-cancer effects. However, its potential role in treating HO remains uncertain.METHODS:Metformin was dissolved into water and given to mice. All the mice in this study were examined by microCT and myeloid cell quantification using flow cytometry. Complex activity kit was used to examine the activity of mitochondrial complexes of myeloid cells.RESULTS:In this study, we discovered that metformin effectively inhibits genetic and traumatic HO formation and progression. Additionally, we observed a significant increase in myeloid cells in the genetic and traumatic HO mouse model compared to uninjured mice. Notably, metformin specifically reduced the infiltration of myeloid cells into the injured sites of the genetic and traumatic HO model mice. Further investigations revealed that metformin targets mitochondrial complex I and suppresses mitochondrial metabolism in myeloid cells.CONCLUSION:These findings suggest that metformin suppresses HO development by potentially downregulating the mitochondrial metabolism of myeloid cells, offering a promising therapeutic option for HO treatment.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

目的 建立miR-100 基因敲除小鼠模型,初步探索miR-100 基因缺失对小鼠造血系统发育的影响.方法 通过将EIIa-Cre-;miR-100fl/fl 小鼠和EIIa-Cre+;miR-100+/+小鼠进行配繁,培育出EIIa-Cre+;miR-100fl/fl(miR-100-/-)小鼠,也就是miR-100 全身敲除小鼠.通过PCR技术以及q-PCR技术鉴定小鼠基因型并验证miR-100 基因在小鼠骨髓和脾的敲除效率.分离小鼠外周血、骨髓、脾,制备单细胞悬液,利用血细胞计数、流式细胞术、甲基纤维素血细胞集落形成实验分析该基因缺失对小鼠造血系统的影响.并通过q-PCR和RNA结合蛋白免疫沉淀实验(RIP)验证miR-100 与Mospd2 之间的关系.结果 PCR和q-PCR结果表明,成功构建miR-100 基因敲除小鼠.血细胞计数、流式细胞术及甲基纤维素血细胞集落形成实验结果表明,miR-100 基因缺失小鼠外周血髓系细胞比例增多,但其对小鼠骨髓和脾的髓系细胞,T/B淋巴细胞、红细胞的比例和绝对细胞计数无影响,并且miR-100 基因缺失对小鼠骨髓造血干祖细胞群体比例和数量及骨髓单个核细胞集落形成能力无影响.q-PCR结果表明,miR-100 缺失可以促进小鼠骨髓细胞中Mospd2 的表达.RIP实验表明,miR-100 以AGO2 蛋白复合物的形式与Mospd2 结合在一起,进而调控Mospd2 的表达.结论 本研究成功建立了miR-100 基因敲除小鼠模型,发现该基因缺失影响小鼠外周血髓系细胞占比,验证了miR-100 与Mospd2 之间的关系.本研究为进一步了解该基因在小鼠造血调控中的作用提供指导.

Objective To explore the regulated function and mechanisms of deubiquitinating enzyme USP10 regulation under physiological conditions. Methods GEO2R and Metascape analyze the differential gene expression and pathway enrichment in microarray (GSE198574) of Usp10+/+ and Usp10-/-neonatal kidney tissues. Western blot and immunohistochemistry are used to measure the expression levels of candidate transcription factors. Co-immunoprecipitation (Co-IP) and GST-pull down assays analyze the interaction between USP10 and the candidate molecules, and deubiquitination experiments verify the regulatory mechanisms of USP10 on target molecules. The expression of cell proliferation marker p21 and apoptosis marker Cleaved-caspase 3 are detected by Western blot. Meanwhile, CCK-8 and plate clonality assays analyze the regulatory functions of USP10 on cell proliferation. Results The TGF-beta/BMP signaling pathway is activated in kidney tissues of Usp10-/-neonatal mice. Physiological deficiency of Usp10 in mice leads to downregulation of Smad ubiquitin-related factor-1 (Smurf1) protein and upregulation of Smad1/5 without affecting their transcription levels. Mechanistically, USP10 interacts with Smurf1 and removes poly-ubiquitylation of Smurf1 which rely on its deubiquitination activity. USP10-deficient promotes the expression of cell cycle inhibitors p21, which is one of the transcriptional target gene of Smad1/5 and inhibits cell proliferation. Conclusion USP10 inhibits TGF-beta/BMP signaling pathway by deubiquitinating and stabilizing Smurf1, thus maintains cell proliferation homeostasis.

目的 构建SHP2E76K突变的小鼠模型,利用其间充质干细胞(MSC)研究激活突变引发的SHP2蛋白相分离对其细胞增殖能力的影响及其机制.方法 将Ptpn11E76K-neo/+的C57BL/6J小鼠与Mx1-cre工具鼠杂交,得到所需要的Mx1-cre;Ptpn11+/+和Mx1-cre;Ptpn11E76K/+小鼠,并对后者注射pI-pC以诱导Cre酶的表达,使Ptpn11在骨髓MSC中突变.从Mx1-cre;Ptpn11+/+和Mx1-cre;Ptpn11E76K/+小鼠体内分离培养MSC,通过细胞免疫荧光染色确定所分离的细胞为MSC.以Ptpn11+/+的MSC为对照组,Ptpn11E76K/+的MSC为实验组,通过加药将两种细胞分成6组:Ptpn11+/+组;Pt-pn11+/++SHP099组;Ptpn11+/++ET070组;Ptpn11E76K/+组;Ptpn11E76K/++SHP099组;Ptpn11E76K/++ET070组.免疫荧光染色法观察6组细胞内SHP2蛋白相分离的差异,Western blot法检测6组MSC中SHP2蛋白表达水平的差异.CCK-8检测相分离被影响之后细胞增殖能力的改变.提取实验组与对照组细胞总蛋白通过Western blot法检测ERK/p-ERK、AMPK/p-AMPK、mTOR/p-mTOR等蛋白的表达水平.结果 小鼠基因型鉴定证实得到Mx1-cre;Pt-pn11E76K/+和Mx1-cre;Ptpn11+/+小鼠并分离出原代Pt-pn11+/+和Ptpn11E76K/+骨髓MSC.与Ptpn11+/+组相比,Pt-pn11E76K/+组的SHP2蛋白产生更多的相分离冷凝物;与Pt-pn11E76K/+组相比,Ptpn11E76K/++SHP099组和Ptpn11E76K/++ET070组SHP2蛋白凝聚成的冷凝物在均明显减少;Western blot检测各组SHP2蛋白表达水平差异无统计学意义;与Pt-pn11+/+组相比,Ptpn11+/++SHP099组和Ptpn11+/++ET070组MSC的增殖能力下降,细胞内p-ERK和p-mTOR蛋白表达减少,p-AMPK蛋白表达增加;与Ptpn11E76K/+组相比,Ptpn11E76K/++SHP099组和Ptpn11E76K/++ET070组MSC的增殖能力下降,细胞内p-ERK和p-mTOR蛋白表达减少,p-AMPK蛋白表达增加.结论 SHP2的相分离通过刺激AMPK-mTOR信号通路的表达参与了SHP2E76K激活突变的MSC的增殖能力改变.

Heterotopic ossification（HO） is the abnormal formation of bone in extraskeletal sites. However, the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear. Here, we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO. Moreover, we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury（dpi）.In contrast, a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi. Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss. We further demonstrated that fetuin-A（Fet A）, which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone, acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization, leading to immunosuppression. Intervention with recombinant Fet A inhibited hyperinflammation and prevented HO and associated bone mass loss. Collectively, our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that Fet A is an immunosuppressor and a potential therapeutic option for the treatment of HO.

Background Macrophages, as innate immune cells, were reported to participate in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. However, the role and mechanism of macrophage dysfunction in H. pylori-associated pediatric gastritis remain unclear. Materials and Methods An RNA-sequencing assay was used to examine the differential gene expression in normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. qPCR assays were applied to verify the expression of target genes. HE staining was performed to identify the occurrence of inflammation in the normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. Western blotting was used to measure the expression of SHP2 in pediatric gastritis tissue. The metabolic profile of macrophages was determined via Seahorse metabolic analysis. Flow cytometry analysis was used to examine the level of reactive oxygen species (ROS). Results We found that H. pylori -infected gastritis tissue exhibited many differentially expressed genes (DEGs) compared to gastritis tissue without H. pylori infection. Moreover, H. pylori -infected gastritis tissue showed many DEGs annotated with an overactive immune response. We identified that tyrosine-protein phosphatase nonreceptor type 11 (PTPN11), which encodes SHP2, was significantly increased in macrophages of H. pylori -infected gastritis tissue. Furthermore, we revealed that SHP2 could activate the glycolytic function of macrophages to promote H. pylori -induced inflammation. The transcription factor SPI1 , as the downstream molecule of SHP2, could be responsible for the regulation of metabolism-associated gene expression and inflammation. Conclusion Our study illustrated the molecular landscape of H. pylori-infected gastritis tissue in children and suggested that the SHP2/SPI1axis could be a novel therapeutic target in H. pylori-induced pediatric gastritis.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-015-0465-3.

Breast cancer development and progression rely not only on the proliferation of neoplastic cells but also on the significant heterogeneity in the surrounding tumor microenvironment. Its unique microenvironment, including tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts (CAFs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a crucial role in the occurrence, growth, and metastasis of breast cancer. However, a detailed understanding of the complex microenvironment in breast cancer remains largely unknown. The unique pattern of breast cancer microenvironment cells has been poorly studied, and neither has the supportive role of these cells in pathogenesis been assessed. Single-cell multiomics biotechnology, especially single-cell RNA sequencing (scRNA-seq) reveals single-cell expression levels at much higher resolution, finely dissecting the molecular characteristics of tumor microenvironment. Here, we review the recent literature on breast cancer microenvironment, focusing on scRNA-seq studies and analyzing heterogeneity and spatial location of different cells, including T and B cells, macrophages/monocytes, neutrophils, and stromal cells. This review aims to provide a more comprehensive perception of breast cancer microenvironment and annotation for their clinical classification, diagnosis, and treatment. Furthermore, we discuss the impact of novel single-cell omics technologies, such as abundant omics exploration strategies, multiomics conjoint analysis mode, and deep learning network architecture, on the future research of breast cancer immune microenvironment.

Bone marrow microenvironment (BMM) has been proven to have benefits for both normal hematopoietic stem cell niche and pathological leukemic stem cell niche. In fact, the pathological leukemia microenvironment reprograms bone marrow niche cells, especially mesenchymal stem cells for leukemia progression, chemoresistance and relapse. The growth and differentiation of MSCs are modulated by leukemia stem cells. Moreover, chromatin abnormality of mesenchymal stem cells is sufficient for leukemia initiation. Here, we summarize the detailed relationship between MSC and leukemia. MSCs can actively and passively regulate the progression of myelogenous leukemia through cell-to-cell contact, cytokine-receptor interaction, and exosome communication. These behaviors benefit LSCs proliferation and survival and inhibit physiological hematopoiesis. Finally, we describe the recent advances in therapy targeting MSC hoping to provide new perspectives and therapeutic strategies for leukemia.

OBJECTIVE:To explore the synergistic effect and metabolic mechanism of chronic arsenic exposure and PTPN11 gain-of-function mutation on tumorigenesis.METHODS:Arsenic-transformed Ptpn11+/+ (WT-As) and Ptpn11D61G/+ -mutant (D61G-As) mouse embryonic fibroblasts (MEFs) were established by chronic treatment of low-dose arsenic. We used cell counting, plate colony and soft agar colony formation, and a nude mouse xenograft model to detect malignant transformation and tumorigenesis in vitro and in vivo. To detect mitochondrial oxidative phosphorylation (OXPHOS), we used Seahorse real-time cell metabolic analysis as well as adenosine triphosphate (ATP) and ROS production assays. Lastly, we examined mTOR signaling pathway changes by western blotting.RESULTS:Low-dose arsenic exposure promoted WT MEFs proliferation and exacerbated malignancy driven by Ptpn11D61G/+ mutation. Additionally, Ptpn11D61G/+ -mutant MEFs exhibited increased mitochondrial metabolism and low-dose arsenic amplified this malignant metabolic activity. Mechanistically, the mTOR signaling pathway was activated in Ptpn11D61G/+ -mutant MEFs and was further phosphorylated in arsenic-treated MEFs expressing Ptpn11D61G/+ . Critically, tumorigenesis induced by the synergistic effect of low-dose arsenic and Ptpn11D61G/+ mutation was prevented by mTOR pathway inhibition via rapamycin.CONCLUSION:This study found that metabolic reprogramming, particularly mitochondrial hyperactivation, is a core mechanism underlying tumorigenesis induced by the synergistic effect of Ptpn11D61G/+ mutation and arsenic exposure. Furthermore, these findings suggested mTOR is a therapeutic target for Ptpn11-associated cancers.

While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.