The associations of early specialization, sports volume, and maturity status with musculoskeletal injury in elite youth football players.

Background: Youth football in schools has experienced rapid growth in China. Despite the increase of players engaging in more frequent, intensive, and organized sports training at their early ages, the controversy over early specialization (ES) still exists. This study aims to: a) investigate the training situation of players in the Chinese School Football Programme and b) examine the associations of early specialization, sports volume, and maturity status with musculoskeletal injury. Methods: A cross-sectional survey was used. Players who participated in the National School Football Winter Camp were invited to fill out a questionnaire that included the data of maturity, ES, sports volume, and injury history (n = 88 boys and n = 90 girls). Results: The results have shown that 80.3% of the athletes were classified as ES, while 19.7% of them were classified as non-ES. Almost all athletes (96%) participated in a sport for more than 8 months in a year. Most athletes (75.8%) spent more than twice of the time on organized sports than leisure activities. 30.3% of the athletes trained on average more hours per week than the number of their ages. Binomial logistic regression models reflected the significant differences in the odds ratios (OR) of reporting a history of injury among athletes with different levels of specialization (p = 0.024) and the OR of reporting a history of leg injury among players with different weekly sports volumes (p = 0.038). Significant differences were also shown in the OR of players reporting foot injuries between players with different maturity states (p = 0.046), and the Chi-squared test showed significant differences in the OR of reporting acute injuries between players with different levels of specialization (p = 0.048) and weekly activity (p = 0.022). No significant differences were found between the remaining variables. Conclusion: Most school football elite players follow the ES pathway even though ES increases the risk of injury, especially acute injury. Pre-pubertal and early pubertal players have a higher incidence of foot injuries. Players who train more hours per week than their ages have more leg injuries and acute injuries. Therefore, priority protection and intervention should be carried out for populations with a high risk of injury.

Effects of plyometric training on kicking performance in soccer players: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to determine the pooled effect size (ES) of plyometric training (PT) on kicking performance (kicking speed and distance) in soccer players depending upon some related factors (i.e., age, gender, skill level, and intervention duration). This study was carried out according to the PRISMA guidelines. Four electronic databases-EBSCO, PubMed, Scopus, and Web of Science-were searched for relevant studies. A total of n = 16 studies yielding 17 ES with n = 553 participants were finally included in the meta-analysis. A random-effects model was used to calculate Hedge's g with a 95% confidence interval (CI), which showed that plyometric training had a large-sized positive effect on soccer kicking performance (g = 0.979, 95% CI [0.606, 1.353], p < 0.001). Subgroup analyses were performed according to participants' characteristics (i.e., age, gender, skill level) and intervention duration, demonstrating no significant differences between these subgroups. The study pointed out that plyometric training is a generally effective method to improve soccer players' kicking performance, which plays a crucial role in passing and shooting actions during games. As for soccer players and strength and conditioning coaches, the plyometric training aiming to enhance kicking performance has valuable implications in practice. Therefore, besides well-known training methods like power training in the weight room, plyometric training could be incorporated into the overall strength and conditioning programs for soccer players to reach high standards of kicking performance.

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma.

Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72.

BACKGROUND: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored. RESULTS: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage. CONCLUSION: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

The effect of the video assistant referee (VAR) on referees' decisions at FIFA Women's World Cups.

Video assistant referee (VAR) has been implemented in women's football, aiming to improve referees' decision-making, but its impact has not yet been analyzed. This study intended to explore how the VAR affects refereeing decisions at Fédération Internationale de Football Association (FIFA) Women's World Cup competitions. The sample includes all 52 matches played in the 2015 tournament before VAR was introduced and all 52 matches played in the 2019 competition where VAR was deployed. For each match, data on ten variables were collected: first half playing time, second half playing time, total playing time, penalties, offsides, fouls, goals, corner kicks, yellow cards, and red cards. The match variables were compared before and after VAR implementation using a Mann-Whitney U test, a Bayesian analysis, a generalized linear model, and a non-clinical magnitude-based inference. The results demonstrated that after VAR was introduced, playing time during the first half [p < 0.001, BF 10 = 547.05, Cohen's d = 1.06, 90%CI (0.71, 1.40)], the second half [p < 0.001, BF 10 = 57.09, Cohen's d = 0.91, 90%CI (0.57, 1.25)], and the entire match [p < 0.001, BF 10 = 1,120.39, Cohen's d = 1.33, 90%CI (0.97, 1.69)] increased significantly with moderate to large effect sizes, while the number of penalties, offsides, and fouls did not vary significantly neither did the number of goals, corner kicks, yellow cards, and red cards. This study has practical implications for professionals in terms of a better understanding of VAR's impact on elite women's football.

Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is a common type of oral cancer, with a relatively poor prognosis and low post-treatment survival rate. Various strategies and novel drugs to treat TSCC are emerging and under investigation. Trichosanthin (TCS), extracted from the root tubers of Tian-Hua-Fen, has been found to have multiple biological and pharmacological functions, including inhibiting the growth of cancer cells. Granzyme B (GrzB) is a common toxic protein secreted by natural killer cells and cytotoxic T cells. Our group has reported that TCS combined with GrzB might be a superior approach to inhibit liver tumor progression, but data relating to the use of this combination to treat TSCC remain limited. The aim of this study was to examine the effectiveness of TCS on TSCC processes and underlying mechanisms. METHODS: First, we screened the potential antitumor activity of TCS using two types of SCC cell lines. Subsequently, a subcutaneous squamous cell carcinoma xenograft model in nude mice was established. These model mice were randomly divided into four groups and treated as follows: control group, TCS treatment group, GrzB treatment group, and TCS/GrzB combination treatment group. Various tumorigenesis parameters, such as Ki67, PCNA, caspase-3, Bcl-2 and VEGFA, et al., were performed to determine the effects of these treatments on tumor development. RESULTS: Screening confirmed that the SCC25 line exhibited greater sensitivity than the SCC15 line to TCS in vitro studies. TCS or GrzB treatment significantly inhibited tumor growth compared with the inhibition seen in the control group. The TCS/GrzB combination inhibited tumor growth more than either drug alone. TCS treatment inhibited tumor proliferation by downregulating Ki67 and Bcl2 protein expression while accelerating tumor apoptosis. In the TCS/GrzB-treated group, expression of Ki67 was further downregulated, while the level of activated caspase-3 was increased, compared with their expression in either of the single drug treatment groups. CONCLUSION: These results suggest that the TCS/GrzB combination could represent an effective immunotherapy for TSCC.

Acute kinematics and kinetics changes to wearable resistance during change of direction among soccer players.

This study determined the acute changes in kinematics and kinetics when an additional load equivalent to 5% body mass was attached to the torso during change of direction (COD). In this within-subject repeated measures study, 14 male soccer players (age: 18.29 ± 0.32 years) volunteered to participate. Subjects performed COD under two conditions in randomized order: (1) no WR, and (2) with WR. No significant differences between the loaded and unloaded conditions in actual COD angle, approach speed, braking time, propulsive time, contact time, COD completion time (all p > 0.05, ES = 0.05-0.11), and all measured kinematic parameters (all p > 0.05, ES = 0-0.18). Nonetheless, ankle plantar/dorsi flexion ROM had possibly small increase in the loaded condition (ES = 0.24). Kinetics analysis has shown that the loaded condition was likely to have small increase in relative peak vertical propulsive ground reaction force (GRF, p = 0.11, ES = 0.41), and possible small increases in relative peak braking GRF (vertical: p = 0.21, ES = 0.42; total: p = 0.22, ES = 0.38), relative peak total propulsive GRF (p = 0.24, ES = 0.26), and relative braking impulse (horizontal, vertical, and total; p = 0.27-0.41, ES = 0.26-0.28). WR did not significantly change the acute movement techniques, meanwhile induced small increases in important kinetic stimuli for potential adaptation in COD.

Astrin: A Key Player in Mitosis and Cancer.

Astrin, which is a spindle-associated protein, was found to be closely related to mitotic spindle formation and maintenance. It interacts with other spindle-related proteins to play a key role in maintaining the attachment of the kinetochore-microtubule and integrity of centrosomes and promoting the centriole duplication. In addition, Astrin was quite recently found to be abnormally highly expressed in a variety of cancers. Astrin promotes the development of cancer by participating in various molecular pathways and is considered as a potential prognostic and survival predictor.

Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

Extracellular Matrix Remodeling During Palate Development.

The morphogenesis of the mammalian secondary plate is a series of highly dynamic developmental process, including the palate shelves vertical outgrowth, elevation to the horizontal plane and complete fusion in the midline. Extracellular matrix (ECM) proteins not only form the basic infrastructure for palatal mesenchymal cells to adhere via integrins but also interact with cells to regulate their functions such as proliferation and differentiation. ECM remodeling is essential for palatal outgrowth, expansion, elevation, and fusion. Multiple signaling pathways important for palatogenesis such as FGF, TGF ß, BMP, and SHH remodels ECM dynamics. Dysregulation of ECM such as HA synthesis or ECM breakdown enzymes MMPs or ADAMTS causes cleft palate in mouse models. A better understanding of ECM remodeling will contribute to revealing the pathogenesis of cleft palate.

Distinct Roles of TRAPPC8 and TRAPPC12 in Ciliogenesis via Their Interactions With OFD1.

The transport protein particle (TRAPP) complex was initially identified as a tethering factor for COPII vesicle. Subsequently, three forms (TRAPPI, II, and III) have been found and TRAPPIII has been reported to serve as a regulator in autophagy. This study investigates a new role of mammalian TRAPPIII in ciliogenesis. We found a ciliopathy protein, oral-facial-digital syndrome 1 (OFD1), interacting with the TRAPPIII-specific subunits TRAPPC8 and TRAPPC12. TRAPPC8 is necessary for the association of OFD1 with pericentriolar material 1 (PCM1). Its depletion reduces the extent of colocalized signals between OFD1 and PCM1, but does not compromise the structural integrity of centriolar satellites. The interaction between TRAPPC8 and OFD1 inhibits that between OFD1 and TRAPPC12, suggesting different roles of TRAPPIII-specific subunits in ciliogenesis and explaining the differences in cilium lengths in TRAPPC8-depleted and TRAPPC12-depleted hTERT-RPE1 cells. On the other hand, TRAPPC12 depletion causes increased ciliary length because TRAPPC12 is required for the disassembly of primary cilia. Overall, this study has revealed different roles of TRAPPC8 and TRAPPC12 in the assembly of centriolar satellites and demonstrated a possible tethering role of TRAPPIII during ciliogenesis.

New ribosome-inactivating proteins and other proteins with protein synthesis-inhibiting activities.

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.

A Naturally Occurring Splice Variant of GGA1 Inhibits the Anterograde Post-Golgi Traffic of α2B-Adrenergic Receptor.

The regulatory mechanisms of cell surface targeting of nascent G protein-coupled receptors (GPCRs) en route from the endoplasmic reticulum through the Golgi remain poorly understood. We have recently demonstrated that three Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding proteins (GGAs) mediate the post-Golgi export of α2B-adrenergic receptor (α2B-AR), a prototypic GPCR, and directly interact with the receptor. In particular, GGA1 interaction with α2B-AR is mediated via its hinge domain. Here we determined the role of a naturally occurring truncated form of GGA1 (GGA1t) which lacks the N-terminal portion of the hinge domain in α2B-AR trafficking and elucidated the underlying mechanisms. We demonstrated that both GGA1 and GGA1t were colocalized and mainly expressed at the Golgi. In marked contrast to GGA1, the expression of GGA1t significantly attenuated the cell surface export of newly synthesized α2B-AR from the Golgi and in parallel receptor-mediated signaling. Furthermore, we found that GGA1t formed homodimers and heterodimers with GGA1. More interestingly, GGA1t was unable to bind the cargo α2B-AR and to recruit clathrin onto the trans-Golgi network. These data provide evidence implicating that the truncated form of GGA1 behaviors as a dominant-negative regulator for the cell surface export of α2B-AR and this function of GGA1t is attributed to its abilities to dimerize with its wide type counterpart and to inhibit cargo interaction and clathrin recruitment to form specialized transport vesicles.

Specific TBC Domain-Containing Proteins Control the ER-Golgi-Plasma Membrane Trafficking of GPCRs.

G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell surface signaling proteins. However, the molecular mechanisms underlying their cell surface delivery after synthesis remain poorly understood. Here, we screen the TBC domain-containing proteins, putative Rab GTPase-activating proteins (GAPs), in the intracellular trafficking of GPCRs and identify several TBC proteins that activity-dependently regulate the anterograde transport, en route from the endoplasmic reticulum to the Golgi or from the Golgi to the cell surface, of several prototypic GPCR members without affecting other plasma membrane proteins. We also show that TBC1D6 functions as a GAP for Rab26, physically associates with Rab26, and attenuates Rab26 interaction with GPCRs. Furthermore, both overexpression and depletion of TBC1D6 inhibit the post-Golgi traffic of GPCRs. These data demonstrate important roles of the TBC proteins in forward trafficking of nascent GPCRs and reveal regulatory mechanisms of GPCR targeting to the functional destination.

Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.

Liver transplantation (LT) is most effective and promising approach for end-stage liver disease. However, there remains room for further improvement and innovation, for example, to reduce ischemic reperfusion injury, transplant rejection and immune tolerance. A good animal model of LT is essential for such innovation in transplant research. Although rat LT model has been used since the last century, it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other. In this study, we for the first time performed LT using the tree shrew (Tupaia belangeri), a species in the Order Scandentia which is closely related with primates, and evaluated the possibility to adopt this species as a new model of LT. We performed LT on 30 animals using the two-cuff technique, examining the success rate, the survival rate and the immunological reaction. The recipient operation time was 60 min averagely, and we limited the time of the anhepatic phase within 20 min. Twenty-seven (90%) of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9), similar to the reaction in human but not in experimental rat. The rest 14 animals that were given rapamycin survived significantly longer (38 days) and half of them survived for 60 days until the end of the study. Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate. More importantly, the tree shrews share similar immunological reaction with human. In addition, previous genomics study found that the tree shrews share more proteins with human. In sum, the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.

Correction: A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C.

[This corrects the article DOI: 10.18632/oncotarget.19960.].

The novel targets of DL-3-n-butylphthalide predicted by similarity ensemble approach in combination with molecular docking study.

BACKGROUND: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke, and may play a neuroprotective role by acting on multiple active targets. The aim of this study was to predict the target proteins of NBP in mammalian cells. METHODS: The similarity ensemble approach search tool (SEArch), one of the commonly used public bioinformatics tools for target prediction, was employed in the experiment. The molecular docking of NBP to target proteins was performed by using the three-dimensional (3-D) crystal structure, substrate free. The software AutoDock Vina was used for all dockings. The binding targets of NBP were illustrated as 3-D and 2-D diagrams. RESULTS: Firstly, the results showed that NBP bounded to the same binding site on NAD(P)H quinone oxidoreductases (NQO1) as the substrate FAD, leading to competitive inhibition for the catalytic site with -7.2 kcal/mol. This might break the 3-D structure of NQO1 and bring about P53 degradation, resulting in a decrease of p53-mediated apoptosis in ischemic brain cells. Secondly, NBP might exert its therapeutic effect on acute ischemic stroke via modulating indoleamine 2,3-dioxygenase (IDO) bioactivity after associating with it. NBP could alleviate the depression following ischemic stroke by inhibiting IDO. Thirdly, NBP might modulate the function of NADH-ubiquinone oxidoreductase by competitively embedding itself into this complex, further affecting mitochondrial respiration in cerebrovascular diseases as an anti-oxidant agent. CONCLUSIONS: Three potential target proteins of NBP were identified, which may provide a novel aspect for better understanding the protective effects of NBP on the nervous system at the molecular level.

A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C.

Lipid droplet (LD) homeostasis involves activities of various RAB small GTPases. Recently, we found RAB40C was one of the RAB proteins regulating LD homeostasis. RAB40C contains a unique SOCS domain that is required for clustering of LDs. However, its precise functional role in LD homeostasis and mechanism of regulation remain largely unknown. In this study, we observed over-accumulation of LDs in cells with RAB40C deleted by Crispr-Cas9 editing. RAB40C appeared to reduce LD accumulation after long term incubation of cells with oleic acid (24 hours). Unexpectedly, we found that Ras GTPase activating protein (GAP), DAB2IP, bound to RAB40C mainly via its GAP domain and could serve as RAB40C GAP. Studies involving overexpression of DAB2IP and its GAP defective mutant and siRNA depletion of DAB2IP all confirmed that DAB2IP negatively regulated the effect of RAB40C on LD homeostasis. These results provide a novel perspective on the regulation of RAB40C and implicate various signalling pathways regulated by DAB2IP, which may play a role in LD homeostasis via RAB40C.

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs.

G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER) to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

Anti-tumor Activity of Toll-Like Receptor 7 Agonists.

Toll-like receptors (TLRs) are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy. This article reviewed the anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations, and mainly focused on small synthetic molecules, including imiquimod, resiquimod, gardiquimod, and 852A, etc.