Facile incorporation of DNA-templated quantum dots for sensitive electrochemical detection of the oral cancer biomarker interleukin-8.

Recent studies reveal a great value of interleukin-8 (IL-8), a pro-inflammatory cytokine, as a potent biomarker for early diagnosis of oral cancer. Herein, a new electrochemical method is proposed to detect IL-8 by facilely incorporating DNA-templated quantum dots (QDs). In principle, target IL-8 is first treated with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) to yield active thiols and then captured by antibody-functionalized magnetic beads (MBs). Thereafter, via the Michael addition reaction between the active thiol and maleimide group, a maleimide-modified DNA probe is linked to the surface of MBs, which can initiate a process of rolling circle amplification. In this way, long-range DNA strands are generated on the MB surface, subsequently recruiting DNA-templated CdTe/CdS QDs (DNA-QDs) to act as electrochemical reporters. By tracing the responses of DNA-QDs, the method allows IL-8 detection in a linear range from 5 to 5000 fg/mL with a detection limit of 3.36 fg/mL. The selectivity, reproducibility, and applicability in complex serum samples are also demonstrated to be favorable, indicating that the method may have a great potential in the future. More importantly, the use of TCEP treatment in the method not only provides a facile way to incorporate DNA-QDs, avoiding the complicated and time-consuming preparation process of antibody-DNA conjugates or functional nanomaterials; but also makes the method capable of being extended to detect other protein biomarkers in view of widespread presence of disulfides, which may hold a broad potential to facilitate efficient biosensing designs.

Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice.

OBJECTIVE: Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. MATERIALS AND METHODS: Dmp1Cre ;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre ;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. RESULTS: Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre ;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. CONCLUSIONS: Augmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.

Biomineralization of dentin.

A single biomineralization of demineralized dentin is significant to restore the demineralized dentin due to dental caries or erosion. In recent years, meaningful progress has been made regarding the mechanisms involved in the biomineralization of dentin collagen. Concepts changing from the classical ion-based crystallization to non-classical particle-based crystallization, inspired a different strategy to infiltrate the demineralized dentin collagen. The remarkable discovery was the report of liquid-like amorphous calcium phosphate as nanoprecursor particles to carbonated hydroxyapatite. The non-collagenous proteins and their analogues are widely investigated, for their key role in controlling mineralization during the process of crystal nucleation and growth. The in-depth studies of the gap zone provided significant improvements in our understanding of the structure of collagen and of the intrafibrillar remineralization of collagen fibrils. The collagen is not a passive substrate as previously supposed, and the active role of guiding nanoprecursor infiltration and mediating its nucleation has been demonstrated. Furthermore, recovery of mechanical properties has been evaluated to determine the effectiveness of dentin remineralization. Finally, the problems regarding the origin formation of the calcium phosphate that is deposited in the collagen, and the exact interactions between the non-collagenous proteins, amorphous calcium phosphate and collagen are still unclear. We reviewed the importance of these findings in enriching our understanding of dentin biomineralization, while addressing certain limitations that are inherent to in vitro studies.

MiR-101-3p inhibits EMT to attenuate proliferation and metastasis in glioblastoma by targeting TRIM44.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS: MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.

LRSSL: predict and interpret drug-disease associations based on data integration using sparse subspace learning.

Motivation: : Exploring the potential curative effects of drugs is crucial for effective drug development. Previous studies have indicated that integration of multiple types of information could be conducive to discovering novel indications of drugs. However, how to efficiently identify the mechanism behind drug-disease associations while integrating data from different sources remains a challenging problem. Results: : In this research, we present a novel method for indication prediction of both new drugs and approved drugs. This method is based on Laplacian regularized sparse subspace learning (LRSSL), which integrates drug chemical information, drug target domain information and target annotation information. Experimental results show that the proposed method outperforms several recent approaches for predicting drug-disease associations. Some drug therapeutic effects predicted by the method could be validated by database records or literatures. Moreover, with L1-norm constraint, important drug features have been extracted from multiple drug feature profiles. Case studies suggest that the extracted drug features could be beneficial to interpretation of the predicted results. Availability and Implementation: https://github.com/LiangXujun/LRSSL. Contact: proteomics@csu.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.

Effect of cyclic uniaxial compressive stress on human dental pulp cells in vitro.

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.

Glycometabolic reprogramming associated with the initiation of human dental pulp stem cell differentiation.

Glycometabolism, particularly mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, plays a central role in cell life activities. Glycometabolism can be reprogrammed to maintain the stemness or to induce the differentiation of stem cells, thereby regulating tissue repair and regeneration. However, research on the glycometabolism of human dental pulp stem cells (hDPSCs) remains scarce. Here, we investigated the relationship between glycometabolic reprogramming and initiation of hDPSC differentiation. We found the differentiation of hDPSCs commenced on day 3 when cells were cultured in mineralized medium. When cell differentiation commenced, mitochondria became elongated with well-developed cristae, and the oxygen consumption rate of mitochondria was enhanced, manifested as an increase in basal respiration, mitochondrial ATP production, and maximal respiration. Interestingly, glycolytic enzyme activities, glycolysis capacity, and glycolysis reserve were also upregulated at this time to match the powerful bioenergetic demands. More importantly, hDPSCs derived from different donors or cultured in various oxygen environments showed similar glycometabolic changes when they began to differentiate. Thus, glycometabolic reprogramming accompanies initiation of hDPSC differentiation and could potentially play a role in the regulation of dental pulp repair.

Novel role of zonula occludens-1: A tight junction protein closely associated with the odontoblast differentiation of human dental pulp cells.

Zonula occludens-1 (ZO-1), a tight junction protein, contributes to the maintenance of the polarity of odontoblasts and junctional complex formation in odontoblast layer during tooth development. However, expression and possible role of ZO-1 in human dental pulp cells (hDPCs) during repair process remains unknown. Here, we investigated the expression of ZO-1 in hDPCs and the relationship with odontoblast differentiation. We found the processes of two adjacent cells were fused and formed junction-like structure using scanning electron microscopy. Fluorescence immunoassay and Western blot confirmed ZO-1 expression in hDPCs. Especially, ZO-1 was high expressed at the cell-cell junction sites. More interestingly, ZO-1 accumulated at the leading edge of lamellipodia in migrating cells when a scratch assay was performed. Furthermore, ZO-1 gradual increased during odontoblast differentiation and ZO-1 silencing greatly inhibited the differentiation. ZO-1 binds directly to actin filaments and RhoA/ROCK signaling mainly regulates cell cytoskeleton, thus RhoA/ROCK might play a role in regulating ZO-1. Lysophosphatidic acid (LPA) and Y-27632 were used to activate and inhibit RhoA/ROCK signaling, respectively, with or without mineralizing medium. In normal cultured hDPCs, RhoA activation increased ZO-1 expression and especially in intercellular contacts, whereas ROCK inhibition attenuated the effects induced by LPA. However, expression of ZO-1 was upregulated by Y-27632 but not significantly affected by LPA after odontoblast differentiation. Hence, ZO-1 highly expresses in cell-cell junctions and is related to odontoblast differentiation, which may contribute to dental pulp repair or even the formation of an odontoblast layer. RhoA/ROCK signaling is involved in the regulation of ZO-1.

Effects of combined exogenous dextranase and sodium fluoride on Streptococcus mutans 25175 monospecies biofilms.

PURPOSE: To investigate the effects of exogenous dextranase and sodium fluoride on a S. mutans monospecies biofilm. METHODS: S. mutans 25175 was grown in tryptone soya broth medium, and biofilm was formed on glass slides with 1.0% sucrose. Exogenous dextranase and sodium fluoride were added alone or together. The biofilm morphology was analyzed by confocal laser scanning microscopy. The effects of the drug on the adhesion and exopolysaccharide production by the biofilms were evaluated by scintillation counting and the anthrone method, respectively. RESULTS: In this study, we found that the structure of initial biofilm and mature biofilm were partly altered by dextranase and high concentrations of sodium fluoride separately. However, dextranase combined with a low concentration of sodium fluoride could clearly destroy the typical tree-like structure of the biofilm, and led to less bacterial adhesion than when the dextranase or fluoride were used alone (P < 0.05). The amounts of soluble and insoluble exopolysaccharide were significantly reduced by combining dextranase with a low concentration of sodium fluoride, much more than when they were used alone (P < 0.05). These data indicate that dextranase and a low concentration of sodium fluoride may have synergistic effects against S. mutans biofilm and suggest the application of a low concentration of sodium fluoride in anticaries treatment.

Systemic lupus erythematosus complicated with Fanconi syndrome: a case report and literature review.

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations. The symptoms of SLE in children are more atypical than adults. Childhood SLE complicated with Fanconi syndrome is extremely rare and even more difficult to diagnose. Case presentation: This article reports a preschool boy with SLE who presented with renal tubular acidosis, accompanied by weakness in both lower limbs, delayed growth, and malnutrition. It was later found that the patient had the complication of Fanconi syndrome with renal tubular acidosis. Ultimately, renal biopsy confirmed lupus nephritis. The patient was treated with corticosteroid combined with mycophenolate mofetil, hydroxychloroquine, and belimumab. The symptoms of the child were relieved. Conclusion: Here we report an extremely rare case of childhood SLE complicated with Fanconi syndrome. There has been no similar clinical report. It is necessary to be alert to the possibility of atypical SLE in children to avoid missed diagnosis and misdiagnosis.

Multi-omics analysis reveals the host-microbe interactions in aged rhesus macaques.

Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host-microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host-microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.

ß-Catenin and Rho GTPases as downstream targets of TGF-ß1 during pulp repair.

TGF-ß1 (transforming growth factor-ß1) plays a central role in regulating proliferation, migration and differentiation of dental pulp cells during the repair process after tooth injury. Our previous study showed that p38 mitogen-activated protein kinase may act downstream of TGF-ß1 signalling to effect the differentiation of dental pulp cells. However, the molecular mechanisms that trigger and regulate the process remain to be elucidated. TGF-ß1 interacts with signalling pathways such as Wnt/ß-catenin and Rho to induce diverse biological effects. TGF-ß1 activates ß-catenin signalling, increases ß-catenin nuclear translocation and interacts with LEF/TCF to regulate gene expression. Morphologic changes in response to TGF-ß1 are associated with activation of Rho GTPases, but are abrogated by inhibitors of Rho-associated kinase, a major downstream target of Rho. These results suggest that the Wnt/ß-catenin and Rho pathways may mediate the downstream events of TGF-ß1 signalling.

Roles of lysophosphatidic acid and the Rho-associated kinase pathway in the migration of dental pulp cells.

During the dental pulp repair process, dental pulp cells (DPCs) migrate to the site of injury and differentiate into odontoblasts or odontoblast-like cells. Although migration of DPCs is an important reparative process, the underlying mechanism remains unknown. The objective of this study was to determine the roles of lysophosphatidic acid (LPA) and the Rho-associated kinase (ROCK) pathway in the migration and morphology of dental pulp cells and alpha smooth muscle actin expression in vitro. We demonstrated that both LPA and ROCK inhibition enhanced cell motility and that their combined effects significantly increased migration rate. LPA induced fine cytoskeleton assembly and increased the level of alpha smooth muscle actin (alpha-SMA). ROCK inhibition by Y-27632 and ROCK-(1+2) small interfering RNA (siRNA) resulted in less actin cytoskeleton formation, a lower alpha-SMA level, a star-like cellular morphology and membrane ruffling. LPA and ROCK inhibition induced activation of another Rho GTPase, Rac, which may explain how LPA and ROCK inhibition increases cellmigration and lamellipodium formation.

Engineered red blood cell membrane for sensitive and precise electrochemical detection of salivary exosomes.

As a kind of promising non-invasive biomarker, exosomes naturally occurring in saliva have recently attracted considerable attention in view of their potential use in the diagnosis of oral diseases. Herein, we propose a new electrochemical method for the sensitive and precise detection of salivary exosomes. A red blood cell membrane (RBCM) engineered with CD63 aptamer is the core element of the method and is used to camouflage a gold electrode, thus giving the electrode superior antifouling and targeting ability. Target exosomes presented in saliva are recognized and captured by the highly specific interaction between the exosomal CD63 and the aptamers engineered in RBCM. Then, silver nanoparticles modified with CD63 aptamers are recruited onto the electrode surface to generate significant electrochemical signals, which enables the sensitive detection of target exosomes. By using human oral squamous cell carcinoma CAL27 cell-derived exosomes as a model, the method allows target salivary exosome detection in a wide linear range from 5 × 102 to 1 × 106 particles per mL and a low detection limit of 2.07 × 102 particles per mL. Moreover, the method displays good reproducibility and is feasible for detecting target exosomes with high precision in saliva samples. Overall, the method may provide a useful tool for salivary exosome detection and may have great potential for practical use in the clinical diagnosis of oral diseases.

Role of connexin 43 in odontoblastic differentiation and structural maintenance in pulp damage repair.

Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp-dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.

Coupling of Cell Surface Biotinylation and SILAC-Based Quantitative Proteomics Identified Myoferlin as a Potential Therapeutic Target for Nasopharyngeal Carcinoma Metastasis.

Distant metastasis is a major cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Cell surface proteins represent attractive targets for cancer diagnosis or therapy. However, the cell surface proteins associated with NPC metastasis are poorly understood. To identify potential therapeutic targets for NPC metastasis, we isolated cell surface proteins from two isogenic NPC cell lines, 6-10B (low metastatic) and 5-8F (highly metastatic), through cell surface biotinylation. Stable isotope labeling by amino acids in cell culture (SILAC) based proteomics was applied to comprehensively characterize the cell surface proteins related with the metastatic phenotype. We identified 294 differentially expressed cell surface proteins, including the most upregulated protein myoferlin (MYOF), two receptor tyrosine kinases(RTKs) epidermal growth factor receptor (EGFR) and ephrin type-A receptor 2 (EPHA2) and several integrin family molecules. These differentially expressed proteins are enriched in multiple biological pathways such as the FAK-PI3K-mTOR pathway, focal adhesions, and integrin-mediated cell adhesion. The knockdown of MYOF effectively suppresses the proliferation, migration and invasion of NPC cells. Immunohistochemistry analysis also showed that MYOF is associated with NPC metastasis. We experimentally confirmed, for the first time, that MYOF can interact with EGFR and EPHA2. Moreover, MYOF knockdown could influence not only EGFR activity and its downstream epithelial-mesenchymal transition (EMT), but also EPHA2 ligand-independent activity. These findings suggest that MYOF might be an attractive potential therapeutic target that has double effects of simultaneously influencing EGFR and EPHA2 signaling pathway. In conclusion, this is the first study to profile the cell surface proteins associated with NPC metastasis and provide valuable resource for future researches.

The effects of altered BMP4 signaling in first branchial-arch-derived murine embryonic orofacial tissues.

The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1's cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2+ cells that marked BA1's mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP+ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2+ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.

Interleukin-1ß is a potential therapeutic target for periodontitis: a narrative review.

Interleukin(IL)-1ß, a pro-inflammatory cytokine, was elevated and participates in periodontitis. Not only the link between IL-1ß and periodontitis was proved by clinical evidence, but also the increased IL-1ß triggers a series of inflammatory reactions and promotes bone resorption. Currently, IL-1ß blockage has been therapeutic strategies for autoimmune and autoinflammatory diseases such as rheumatoid arthritis, cryopyrin-associated periodic syndromes, gout and type II diabetes mellitus. It is speculated that IL-1ß be a potential therapeutic target for periodontitis. The review focuses on the production, mechanism, present treatments and future potential strategies for IL-1ß in periodontitis.

China is closely monitoring an increase in infection with avian influenza A (H7N9) virus.

The fifth outbreak of human infection with avian influenza A (H7N9) virus has struck far and wide in China. The number of cases of infection with the avian influenza A (H7N9) suddenly increased in 2013-2014, but the number of cases reported this winter has exceeded the number reported in all previous seasons. Given this situation, the National Health and Family Planning Commission issued updated Chinese guidelines (2017 version) on diagnosis and treatment of infection with the avian influenza A (H7N9) virus on January 24, 2017. In addition, the Chinese Government closed many live poultry markets in urban and rural areas in a number of provinces and the Government has taken proactive measures to surveil, respond to, and prevent potential pandemics involving the avian influenza A (H7N9) virus.