Ag-modified CuO cavity arrays as a SERS-electrochemical dual signal platform for thiram detection.

Rapid and sensitive determination of pesticide residues in fruits and vegetables is critical for human health and ecosystems. This paper used an Ag-modified CuO sphere-cavity array (CuO@Ag) electrode as a thiram SERS/electrochemical dual readout detection platform. Numerous Raman "hotspots" generated by uniformly distributed silver nanoparticles, charge transfer at the CuO@Ag interface, and the formation of Ag-thiram complexes contribute to the significant enhancement of this SERS substrate, which results in excellent SERS performance with an enhancement factor up to 1.42 × 106. When using SERS as the readout technique, the linear range of the substrate for thiram detection was 0.05-20 nM with a detection limit (LOD) of up to 0.0067 nM. Meanwhile, a correlation between the value of change in current density and thiram concentration was established due to the formation of stable complexes of thiram with Cu2+ generated at specific potentials. The linear range of electrochemical detection was 0.05-20.0 µM, and the detection limit was 0.0167 µM. The newly devised dual-readout sensor offers notable sensitivity and stability. The two signal readout methods complement each other in terms of linear range and detection limit, making it a convenient tool for assessing thiram residue levels in agro-food. At the same time, the combination of commercially available portable equipment makes on-site monitoring possible.

Development and Validation of Nomogram for the Prediction of Malignant Ventricular Arrhythmia Including Circulating Inflammatory Cells in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Background: Malignant ventricular arrhythmia (MVA) can seriously affect the hemodynamic changes of the body. In this study, we developed and validated a nomogram to predict the in-hospital MVA risk in patients with STEMI after emergency PCI. Methods: The multivariable logistic regression analysis included variables with a P<0.05 in the univariate logistic regression analysis and investigated the independent predictors affecting in-hospital MVA after PCI in patients with STEMI in the training cohort. The construction of a nomogram model used independent predictors to predict the risk of in-hospital MVA, and C-index, Hosmer-Lemeshow (HL) test, calibration curves, decision curve analysis (DCA), and receiver operating characteristic (ROC) were used to validate the nomogram. Results: Killip class [OR=5.034 (95% CI: 1.596-15.809), P=0.005], CK-MB [OR=1.002 (95% CI: 1.001-1.004), P=0.022], serum potassium [OR=0.618 (95% CI: 0.406-0.918), P=0.020], NLR [OR=1.073 (95% CI: 1.034-1.115), P<0.001], and monocyte [OR=1.974 (95% CI: 1.376-2.925), P<0.001] were the independent predictors of in-hospital MVA after PCI in patients with STEMI. A nomogram including the 5 independent predictors was developed to predict the risk of in-hospital MVA. The C-index, equivalent to the area under the ROC curve (AUC), was 0.803 (95% confidence interval [CI]: 0.738-0.868) in the training cohort, and 0.801 (95% CI:0.692-0.911) in the validation cohort, showing that the nomogram had a good discrimination. The HL test (χ2=8.439, P=0.392 in the training cohort; χ2=9.730, P=0.285 in the validation cohort) revealed a good calibration. The DCA suggested an obvious clinical net benefit. Conclusion: Killip class, CK-MB, serum potassium, NLR, and monocyte were independent factors for in-hospital MVA after PCI in patients with STEMI. The nomogram model constructed based on the above factors to predict the risk of in-hospital MVA had satisfactory discrimination, calibration, and clinical effectiveness, and was an excellent tool for early prediction of the risk of in-hospital MVA after PCI in patients with STEMI.

Diallyl trisulfide inhibits gastric cancer stem cell properties through ΔNp63/sonic hedgehog pathway.

Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ΔNp63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ΔNp63/SHH pathway. We found that ΔNp63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ΔNp63 elevated the self-renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ΔNp63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ΔNp63 upregulation through SHH pathway activation. These findings illustrated the role of ΔNp63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ΔNp63/SHH pathway.

Association between screen time and suspected developmental coordination disorder in preschoolers: A national population-based study in China.

Introduction: Excessive screen exposure (ESE) is a growing global public health concern. This study aims to investigate the potential association between ESE and suspected developmental coordination disorder (DCD) in Chinese pre-schoolers, with or without siblings. Method: A retrospective cohort study was conducted, involving 126,433 children from 551 cities in China. The Little Developmental Coordination Disorder Questionnaire (LDCDQ) was employed to evaluate motor impairment in children, while parents provided information on their children's screen time in the past year. A mixed and multi-level logistic regression model was used to analyze the associations of all screen exposure measurements from the past year with LDCDQ scores and the risk of suspected DCD. Results: The prevalence of excessive screen exposure was 67.6% (>1 h per day) and 28.9% (>2 h per day) in Chinese pre-schoolers. One hour's increase in weekday daily screen time, weekend daily screen time, and screen time before sleep in the past year was associated with a decreased total score of the LDCDQ (ß were -0.690, -0.398, and -1.587, p < 0.001) and an increased risk of suspected DCD by 15.3%, 9.1%, and 46.8% when adjusting for the child, family and maternal health characteristics. Excessive screen exposure decreased the total LDCDQ scores by 1.335 (>1 vs. ≤1 h) and 1.162 (>2 vs. ≤2 h) and increased risks of suspected DCD by 44.0% (>1 vs. ≤1 h) and 31.1% (>2 vs. ≤2 h) with statistical significance (each p < 0.05). The stratified analysis showed that the association between screen time and LDCDQ score was stronger in children without siblings than in those with siblings. Conclusion: The risk of suspected DCD was highest for screen time exposure before bed compared with average weekday and weekend exposures. Parents should be advised to prevent their children from using electronic screens unsupervised, especially in one-child families.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

Sulforaphane ameliorates bisphenol A-induced hepatic lipid accumulation by inhibiting endoplasmic reticulum stress.

The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) - induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.

Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3-10 years.

BACKGROUND: This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0-36+6 gestational week), and early-term (37+0-38+6 gestational week) children compared to their full-term peers with a national population-based sample in China. METHODS: A total of 1673 children (799 girls, 874 boys) aged 3-10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model. RESULTS: The global motor performance [ß = - 5.111, 95% confidence interval (CI) = - 9.200 to - 1.022; P = 0.015] and balance (ß = - 5.182, 95% CI = - 5.055 to - 1.158; P = 0.003) for very and moderately preterm children aged 3-6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3-6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067-8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05). CONCLUSIONS: Our findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.

An ER-targeted "reserve-release" fluorogen for topological quantification of reticulophagy.

The endoplasmic reticulum's (ER) dynamic nature, essential for maintaining cellular homeostasis, can be influenced by stress-induced damage, which can be assessed by examining the morphology of ER dynamics and, more locally, ER properties such as hydrophobicity, viscosity, and polarity. Although numerous ER-specific chemical probes have been developed to monitor the ER's physical and chemical parameters, the quantitative detection and super-resolution imaging of its local hydrophobicity have yet to be explored. Here, we describe a photostable ER-targeted probe with high signal-to-noise ratio for super-resolution imaging that can specifically respond to changes in ER hydrophobicity under stress based on a "reserve-release" mechanism. The probe shows an excellent ability to target ER over commercial ER dyes and can be used to track local changes of hydrophobicity by fluorescence intensity and morphology during the selective autophagy of ER (i.e., reticulophagy). By correlating the level and location of ER damage with the distribution of fluorescence intensity, we were able to assess reticulophagy at the subcellular level. Beyond that, we developed a topological analytical tool adaptable to any ER probe for detecting structural changes in ER and thus quantitatively identifying reticulophagy. The algorithm-assisted tool can also be adapted to a wide range of molecular probes and organelles. Altogether, the new probe and analytical strategy described here show promise for the quantitative detection and analysis of subtle ER damage and stress.

Isothiocyanates attenuate immune checkpoint blockage therapy in gastric cancer via induction of PD-L1 expression.

The PD-1/PD-L1 immune checkpoint blockade therapy has shown revolutionary efficacy in the treatment of multiple cancers including gastric cancer. Isothiocyanates play important roles in cancer cell suppression and immunomodulation. However, the effects of isothiocyanates on immune checkpoint inhibitors are poorly understood in gastric cancer. The influence of three major isothiocyanates (sulforaphane, phenylethyl isothiocyanate, and benzhydryl isothiocyanate) on gastric cancer cell growth and PD-L1 expression was investigated. Syngeneic mouse models were administered by isothiocyanates and anti-PD-L1 monoclonal antibody, and the anti-tumor effects were assessed. The expression of PD-L1, proportion of lymphocytes and serum cytokine levels were detected to explore the underlying mechanisms. We found that PD-L1 expression was significantly induced by isothiocyanates which was associated with TAp63α up-regulation. We further revealed that TAp63α promoted PD-L1 through transcriptional activation. Combination treatment of isothiocyanates and anti-PD-L1 therapy weakened the sensitivity of gastric cancer cells to anti-PD-L1 drug. Moreover, in vivo studies illustrated that the interference effects of isothiocyanates on anti-PD-L1 antibody were related to PD-L1 expression and decreased infiltrating T lymphocytes in tumor bearing mouse hosts. Our findings provide novel insights as isothiocyanates could interfere with the successful application of immunotherapy in gastric cancer.

Super-Resolution Imaging of Mitochondrial HClO during Cell Ferroptosis Using a Near-Infrared Fluorescent Probe.

Ferroptosis is of great importance in physiological and pathological processes, which is associated with various inflammation-related diseases, cardiovascular diseases, and even cancer. Ferroptosis can cause abnormal change of reactive oxygen species (ROS) in mitochondria. Hypochlorous acid (HClO) acts as a typical ROS. Therefore, it is needed to study the relationship between mitochondrial morphology and HClO changes during ferroptosis at the subcellular level. To this end, a near-infrared-excitation/emission fluorescent probe, HD-Br-1, for rapid detection of mitochondrial HClO was developed based on the specific oxidative cleavage of the N,N-dimethylthiocarbamate moiety. The fluctuation in mitochondrial HClO content and the change in mitochondrial morphology during ferroptosis were monitored in real time by super-resolution imaging. In addition, HD-Br-1 was successfully applied to monitor exogenous and endogenous mitochondrial HClO during cell ferroptosis and visualize tumor to discriminate from healthy tissues. Therefore, we believe that HD-Br-1 could provide a valuable approach for the detection of mitochondrial HClO in cancer cells as well as for understanding the ferroptosis mechanism and early diagnosis of cancers associated with ferroptosis for future research.

Magnesium isoglycyrrhizinate ameliorates lipopolysaccharide-induced liver injury by upregulating autophagy and inhibiting inflammation via IL-22 expression.

Liver disease has become a major cause of premature mortality worldwide. It is well known that dysregulated inflammation response plays a crucial role in most liver diseases. As a Chinese medicinal herb, Magnesium isoglycyrrhizinate (MgIG) has been proven to have good hepatoprotective activity and has been used in clinic to treat liver disease. However, the mechanisms by which MgIG regulates LPS-induced liver injury and inflammation in vivo remain elusive. In our study, MgIG pretreatment mitigated LPS-induced liver damage by suppressing apoptosis and inflammation via regulating macrophage/neutrophil infiltration. MgIG ameliorated the effects of LPS on pro-oxidant enzymes (NOX1/2/4) and anti-oxidant enzymes (SOD1/2). Interestingly, we found that the level of the hepatoprotective cytokine interleukin (IL)-22 was significantly upregulated in MgIG-treated liver tissues, which might be a potential mechanism of MgIG against liver injury. Moreover, we found that MgIG treatment not only inhibited TLR4/MyD88/NF-κB signaling pathway, but also activated autophagy. Furthermore, IL-22 treatment activated autophagy and inhibited TLR4/NF-κB signaling pathway in vitro, suggesting that IL-22-activated autophagy and -inhibited inflammation also participated in the protective effects of MgIG. Altogether, our results uncovered the potential mechanisms of the hepatoprotective effects of MgIG, which provided critical evidence to support the use of MgIG to prevent and treat liver diseases.

An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Molecule Reveals Zn2+ Micro-Dynamics During Drug-Induced Organelle Ionic Disorder.

The endoplasmic reticulum (ER) is the main storage site of Zn2+, and Zn2+ plays an important role in regulating ER homeostasis. Therefore, we designed and synthesized a ratiometric fluorescent Zn2+ probe ER-Zn targeting ER stress. The probe displayed a specific Zn2+ induced blue shift at the spectral maximum values of excitation (80 nm) and emission (30 nm). The ratio imaging capability of Zn2+ under dual excitation mode can be applied not only to quantitative and reversible detection of exogenous Zn2+, but also the observation of the Zn2+ level change under ER stress, elucidating the different behaviors of Zn2+ release in ER stimulated by tunicamycin and thapsigargin. Additionally, the NIR imaging capability of ER-Zn provides an important basis for further research on animal models and is expected to realize the visualization and treatment of ER stress-related diseases through the regulation of ER stress by Zn2+. We envision that this probe can be applied to screen drugs for diseases related to ER stress regulation.

ΔNp63α mediates sulforaphane suppressed colorectal cancer stem cell properties through transcriptional regulation of Nanog/Oct4/Sox2.

Cancer stem cells (CSCs) play a key role in cancer initiation, development, metastasis, and recurrence. Previously, we found that sulforaphane (SFN), a natural compound obtained from cruciferous vegetables, inhibited colorectal CSCs via the downregulation of TAp63α. However, the role of ΔNp63α, another critical isoform of p63 which has been considered to contribute to cancer progression, in SFN-mediated colorectal CSCs inhibition remains unclear. Here, we showed that ΔNp63α expression was enhanced in sphere-forming colorectal cancer cells. Overexpression of ΔNp63α promoted the properties of CSCs, while downregulation of ΔNp63α suppressed those properties. Besides, ΔNp63α was found to activate the transcription of core CSCs genes including Nanog, Oct4, and Sox2. Furthermore, in vitro and in vivo experiments illustrated the regulatory effects of SFN on ΔNp63α and colorectal CSCs. These findings suggested for the first time that ΔNp63α activated the transcription of Nanog, Oct4, Sox2 and mediated the interventional effects of SFN on colorectal CSCs, thus providing a novel mechanism by which SFN inhibits colorectal CSCs.

Bacterial mandelic acid degradation pathway and its application in biotechnology.

Mandelic acid and its derivatives are an important class of chemical synthetic blocks, which is widely used in drug synthesis and stereochemistry research. In nature, mandelic acid degradation pathway has been widely identified and analysed as a representative pathway of aromatic compounds degradation. The most studied mandelic acid degradation pathway from Pseudomonas putida consists of mandelate racemase, S-mandelate dehydrogenase, benzoylformate decarboxylase, benzaldehyde dehydrogenase and downstream benzoic acid degradation pathways. Because of the ability to catalyse various reactions of aromatic substrates, pathway enzymes have been widely used in biocatalysis, kinetic resolution, chiral compounds synthesis or construction of new metabolic pathways. In this paper, the physiological significance and the existing range of the mandelic acid degradation pathway were introduced first. Then each of the enzymes in the pathway is reviewed one by one, including the researches on enzymatic properties and the applications in biotechnology as well as efforts that have been made to modify the substrate specificity or improving catalytic activity by enzyme engineering to adapt different applications. The composition of the important metabolic pathway of bacterial mandelic acid degradation pathway as well as the researches and applications of pathway enzymes is summarized in this review for the first time.

Association of Maternal Dietary Patterns during Gestation and Offspring Neurodevelopment.

The health effects of diet are long term and persistent. Few cohort studies have investigated the influence of maternal dietary patterns during different gestational periods on offspring's health outcomes. This study investigated the associations between maternal dietary patterns in the mid- and late-gestation and infant's neurodevelopment at 1 year of age in the Jiangsu Birth Cohort (JBC) Study. A total of 1178 mother-child pairs were available for analysis. A semiquantitative food frequency questionnaire (FFQ) was used to investigate dietary intake at 22-26 and 30-34 gestational weeks (GWs). Neurodevelopment of children aged 1 year old was assessed using Bayley-Ⅲ Screening Test. Principal component analysis (PCA) and Poisson regression were used to extract dietary patterns and to investigate the association between dietary patterns and infant neurodevelopment. After adjusting for potential confounders, the maternal 'Aquatic products, Fresh vegetables and Homonemeae' pattern in the second trimester was associated with a lower risk of being non-competent in cognitive and gross motor development, respectively (cognition: aRR = 0.84; 95% CI 0.74-0.94; gross motor: aRR = 0.80; 95% CI 0.71-0.91), and the similar pattern, 'Aquatic products and Homonemeae', in the third trimester also showed significant association with decreased risk of failing age-appreciate cognitive and receptive communication development (cognition: aRR = 0.89; 95% CI 0.80-0.98; receptive communication: aRR = 0.91; 95% CI 0.84-0.99). Notably, adherence to the dietary pattern with relatively high aquatic and homonemeae products in both trimesters demonstrated remarkable protective effects on child neurodevelopment with the risk of being non-competent in cognitive and gross motor development decreasing by 59% (95% CI 0.21-0.79) and 63% (95% CI 0.18-0.77), respectively. Our findings suggested that adherence to the 'Aquatic products and Homonemeae' dietary pattern during pregnancy may have optimal effects on offspring's neurodevelopment.

Interleukin-17A mediates tobacco smoke-induced lung cancer epithelial-mesenchymal transition through transcriptional regulation of ΔNp63α on miR-19.

Interleukin-17A (IL-17A) is an essential inflammatory cytokine in the progress of carcinogenesis. Tobacco smoke (TS) is a major risk factor of lung cancer that influences epithelial-mesenchymal transition (EMT) process. However, the potential mechanism by which IL-17A mediates the progression of lung cancer in TS-induced EMT remains elusive. In the present study, it was revealed that the IL-17A level was elevated in lung cancer tissues, especially in tumor tissues of cases with experience of smoking, and a higher IL-17A level was correlated with induction of EMT in those specimens. Moreover, the expression of ΔNp63α was increased in IL-17A-stimulated lung cancer cells. ΔNp63α functioned as a key oncogene that bound to the miR-17-92 cluster promoter and transcriptionally increased the expression of miR-19 in lung cancer cells. Overexpression of miR-19 promoted EMT in lung cancer with downregulation of E-cadherin and upregulation of N-cadherin, while its inhibition suppressed EMT. Finally, the upregulated levels of IL-17A, ΔNp63α, and miR-19 along with the alteration of EMT-associated biomarkers were found in lung tissues of TS-exposed mice. Taken together, the abovementioned results suggest that IL-17A increases ΔNp63α expression, transcriptionally elevates miR-19 expression, and promotes TS-induced EMT in lung cancer. These findings may provide a new insight for the identification of therapeutic targets for lung cancer.

Progress of metabolic engineering for the production of eicosapentaenoic acid.

Eicosapentaenoic Acid (EPA) is an essential ω-3 polyunsaturated fatty acid for human health. Currently, high-quality EPA production is largely dependent on the extraction of fish oil, but this unsustainable approach cannot meet its rising market demand. Biotechnological approaches for EPA production from microorganisms have received increasing attention due to their suitability for large-scale production and independence of the seasonal or climate restrictions. This review summarizes recent research on different microorganisms capable of producing EPA, such as microalgae, bacteria, and fungi, and introduces the different EPA biosynthesis pathways. Notably, some novel engineering strategies have been applied to endow and improve the abilities of microorganisms to synthesize EPA, including the construction and optimization of the EPA biosynthesis pathway, an increase in the acetyl-CoA pool supply, the increase of NADPH and the inhibition of competing pathways. This review aims to provide an updated summary of EPA production.

Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting the Sonic Hedgehog Pathway.

The presence of gastric cancer stem cells (GCSCs) marks the onset of gastric carcinoma. The sonic hedgehog (SHH) pathway plays a vital role in the maintenance of GCSC characteristics. Apatinib has been approved in China for advanced gastric cancer (GC) treatment. However, whether apatinib can target GCSCs and affect the SHH pathway remains unclear. The present study aimed to investigate the underlying mechanism of apatinib's antitumor effects on GC. The expression levels of GCSC markers and number of CD133+ cells were significantly elevated in the sphere-forming cells. Apatinib effectively suppressed GCSC traits by inhibiting tumorsphere formation and cell proliferation, suppressing GCSC markers expression and CD133+ cell number, and inducing apoptosis. Apatinib downregulated the activation of the SHH pathway; while upregulation of the SHH pathway attenuated the inhibitory effects of apatinib on GCSCs. Moreover, apatinib treatment significantly delayed tumor growth and inhibited GCSC characteristics in the xenograft model. Our data suggested that apatinib exhibited inhibitory effects on GCSCs by suppressing SHH pathway both in vitro and in vivo, thus providing new insights into the therapeutic application of apatinib in GCSC suppression and advanced gastric cancer treatment.