In Situ H-Radical Surface Treatment on Aluminum Gallium Nitride for High-Performance Aluminum Gallium Nitride/Gallium Nitride MIS-HEMTs Fabrication.

In this work, we demonstrated a low current collapse normally on Al2O3/AlGaN/GaN MIS-HEMT with in situ H-radical surface treatment on AlGaN. The in situ atomic pretreatment was performed in a specially designed chamber prior to the thermal ALD-Al2O3 deposition, which improved the Al2O3/AlGaN interface with Dit of ~2 × 1012 cm-2 eV-1, and thus effectively reduced the current collapse and the dynamic Ron degradation. The devices showed good electrical performance with low Vth hysteresis and peak trans-conductance of 107 mS/mm. Additionally, when the devices operated under 25 °C pulse-mode stress measurement with VDS,Q = 40 V (period of 1 ms, pulse width of 1 µs), the dynamic Ron increase of ~14.1% was achieved.

A Novel NDT Scanning System Based on Line Array Fast Neutron Detector and D-T Neutron Source.

A novel non-destructive testing scanning system based on a large-size line array fast neutron detector and compact D-T neutron source has been constructed. The scanning range is up to 1000 mm, and the resolution is better than 1 mm. The fast neutron detection subsystem consists of a polypropylene zinc sulfide scintillator embedded with wavelength-shifting fibers, coupled with a light lens and a scientific CCD camera. With a new rotating tritium target, the lifetime of the compact D-T neutron source could achieve ten hours. The experimental results indicate that the scanning method based on line array fast neutron detector and D-T neutron source is feasible and enables the detection of slits on the order of 0.5 mm in width. Fast neutron tomography has been realized by this detection system too.

Dearomatization-rearomatization strategy of tyrosine for peptide/protein modification through thiol-addition reactions.

We have developed a dearomatization-rearomatization strategy for the modification of peptides/proteins through a thiol-Michael addition to the electrophilic cyclohexadienone intermediate that is generated in situ via the oxidation of tyrosine. This strategy enriches the conjugation toolbox and has great potential for applications in medicinal chemistry and chemical biology.

Association of Pulse Pressure Difference and Diabetes Mellitus in Chinese People: A Cohort Study.

PURPOSE: Here, we sought to determine the association between pulse pressure difference and the incidence of type 2 diabetes mellitus (T2DM) in Chinese people. METHODS: This study involved 211,814 participants among whom 4156 had been diagnosed with T2DM. The correlation between pulse pressure difference and T2DM incidence in Chinese people was determined by multivariate analysis. A smooth curve fitting diagram was then used to explore correlation between pulse pressure difference and T2DM incidence. Finally, the inflection point in the correlation between pulse pressure difference and the T2DM incidence was located by piecewise linear regression. RESULTS: To understand the relationship, adjustments were made for sex, age, total serum cholesterol (TC), fasting blood glucose (FPG), triglyceride (TG), alanine aminotransferase (ALT), family history of diabetes, body mass index (BMI), blood urea nitrogen (BUN), drinking status, and smoking status. Diabetes incidence increased by 0.3% [HR 1.003 (1.001, 1.005), p = <0.05] for every 1mmHg increase in pulse pressure difference. Smooth curve analysis showed that, when pulse pressure difference was ≤35mmHg, diabetes incidence negatively correlated to pulse pressure difference [HR 0.972 (0.953, 0.972) p = 0.053]. However, when pulse pressure difference was >35mmHg, diabetes incidence increased with increasing pulse pressure difference [HR 1.044 (1.042, 1.047) p = <0.001]. And between pulse pressure difference and fasting blood glucose in the final visit, the blood glucose level increased with the elevation of pulse pressure. CONCLUSION: The risk of diabetes was lowest at about 35mmHg pulse pressure difference.

[Determination of silanol group content on the surface of fumed silica by chemical reaction-headspace gas chromatography].

Fumed silica is prepared by flame pyrolysis, where silicon halide is combusted in an oxygen-hydrogen flame, resulting in finely dispersed and thermally stable silicon dioxide. Because of its unique physical and chemical properties, including high porosity, large pore volumes, large specific area, and high chemical activity, fumed silica is widely used in rubbers, plastics, adhesives, paints, and printing inks for reinforcement, as well as in thixotropy, anti-setting, and anti-sagging applications. These functional properties of fumed silica are related to the silanol group on its surface. However, there is no accurate and convenient test method to determine the silanol group content on the surface of fumed silica. This work explores a novel method to determine the silanol group content on the surface of fumed silica by chemical reaction-headspace gas chromatography (HS-GC). Theoretically, by this method, the silanol group can rapidly react with the Grignard reagent and generate methane, the amount of which can be determined accurately by GC analysis. GC analysis was conducted using a headspace flask as a closed reactor to transform the silanol group into a volatile component through a chemical reaction, so as to realize the accurate determination of silica hydroxyl. The amount of methane produced in the reaction was directly proportional to the content of silanol groups on the surface of fumed silica. Therefore, the silanol group content was calculated using the chemical reaction equation. Before the experiment, fumed silica was dried for 2 h in an oven at 105 ℃ to remove adsorbed moisture. The dried fumed silica sample was then reacted with the Grignard reagent dispersed in toluene in an airtight reaction bottle. Toluene was used as a dispersion agent to promote contact and reaction between the fumed silica sample and Grignard reagent. The methane produced by the reaction was injected into a gas chromatograph for separation and further detected using a flame ionization detector (FID). Methane was quantified from the peak areas of the GC signals using the external standard method, and the silanol content in the sample was obtained. Simultaneously, factors influencing the outcome of the method, such as the dosage of the Grignard reagent and reaction time with it, were optimized by a comparison test. Accordingly, 2.0 mL of 0.3 mol/L Grignard reagent and a reaction time of 15 min were found to be optimal for testing. The test results showed that there was good linear correlation between the content of the silanol group and the GC signals, with a correlation coefficient of 0.9990. The limit of detection was 0.30 mg/g, and the limit of quantification was 1.00 mg/g. The relative standard deviation of reproducibility was less than 3%. Based on an interlaboratory test conducted by four laboratories on five samples with different silanol group contents, the repeatability limit (r) was less than 2.5%, and the reproducibility limit (R) was less than 6.5%. Compared with the traditional chemical method, the method involving HS-GC presents distinct advantages in terms of lower reagent consumption, high sensitivity, good stability, and reliability. It is suitable for the rapid detection of the silanol group content on the surface of fumed silica, and can aid in the quality control of fumed silica during its production and application. This method has important theoretical and practical significance for developing accurate methods to determine silica hydroxyl in the silicon industry for standards and the optimization of industrial technology. This study serves as a foundation to standardize and promote the rapid development of silicon material-related industries.

A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo.

Aurora kinase A (Aurora A) plays a critical role in regulating cell mitotic progression and has been considered as a promising drug target for cancer therapy. To develop a novel molecule targeting Aurora A with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide (PIP) Hoechst conjugate, PIP-Ht, targeting to a cell-cycle regulated DNA sequence locating at the promoter of human Aurora A gene (AURKA). PIP-Ht potently suppressed AURKA promoter activities, mRNA expression and protein level, induced tumor cell cycle delay and inhibited tumor cell proliferation in vitro. Furthermore, subcutaneous injection of PIP-Ht into mice bearing human cancer xenografts induced significant tumor growth suppression and cell apoptosis. Collectively, PIP-Ht exhibits the potential as an effective therapeutic candidate for the tumor treatment.

Identification of P2RY13 as an immune-related prognostic biomarker in lung adenocarcinoma: A public database-based retrospective study.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading histological subtype of non-small cell lung cancer (NSCLC). METHODS: In the present study, the gene matrixes of LUAD were downloaded from The Cancer Genome Atlas to infer immune and stromal scores with the 'Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data' (ESTIMATE) algorithm and identified immune-related differentially expressed genes (DEGs) between the high- and low-stromal/immune score groups. Next, all DEGs were subjected to univariate Cox regression and survival analyses to screen out prognostic biomarkers in the tumor microenvironment (TME), and were validated in the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to assess the level of tumor-infiltrating immune cells (TIICs) and immune functions, and GSEA was used to identified pathways altered by prognostic biomarkers. RESULTS: Survival analysis showed that LUAD in the high-immune and stromal score group had a better clinical prognosis. A total of 303 immune-related DEGs were detected. Univariate Cox regression and survival analyses revealed that P2Y purinoceptor 13 (P2RY13) was a favorable factor for the prognosis of LUAD. ssGSEA and Spearman correlation analysis demonstrated that P2RY13 was highly correlated with various TIICs and immune functions. Several immune-associated pathways were enriched between the high- and low-expression P2RY13 groups. CONCLUSION: P2RY13 may be a potential prognostic indicator and is highly associated with the TME in LUAD. However, further experimental studies are required to validate the present findings.

Identification of a ferroptosis-related gene signature (FRGS) for predicting clinical outcome in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Ferroptosis, an oxidative, iron-dependent form of necrotic cell death, is highly associated with tumorigenesis and cancer progression. However, the prognostic value of ferroptosis progress in LUAD was still rarely be investigated. METHODS: Herein, we collected three mRNA expression profiles and 85 ferroptosis-related genes from public databases. The "limma" package was used to identify ferroptosis-related differentially expressed genes (DEGs). Univariate Cox regression analysis and LASSO regression analysis were applied to screen and develop a ferroptosis-related gene signature (FRGS) and a formula to calculate the risk score. Multivariate Cox regression analysis was implemented to determine independent prognostic predictors of overall survival (OS). The area under the receiver operating characteristic curve (AUC) and calibration plot were used to evaluate the predictive accuracy of the FRGS and nomogram. RESULTS: We developed a FRGS with five genes (CYBB, CISD1, FADD, SAT2, VDAC2). The AUC of the FRGS in TCGA cohort was 0.777 at 1-year, 0.721 at 3-year and 0.725 at 5-year, significantly superior to the AUC of TNM stage (1-year: 0.701, 3-year: 0.691, 5-year: 0.686). A similar phenomenon was observed in GEO cohort 1 and 2. Multivariate Cox regression analysis indicted TNM stage and risk score were independent prognostic predictors. Finally, we built a nomogram with TNM stage and FRGS, the AUCs of which markedly higher than that of FRGS or TNM stage alone. CONCLUSION: We constructed a prognostic FRGS with five ferroptosis-related genes and a nomogram for predicting the 1-, 3- and 5-year survival rate of LUAD patients, which may provide a new understanding of the prognostic value of ferroptosis progress in LUAD and will benefit prognosis assessment of LUAD patients.

Tyrosine-Specific Modification via a Dearomatization-Rearomatization Strategy: Access to Azobenzene Functionalized Peptides.

Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides. This method enriches the postsynthetic modification toolbox of peptides and has great potential to be applied in medicinal chemistry and chemical biology.

Coibamide A kills cancer cells through inhibiting autophagy.

Natural products are useful tools for biological mechanism research and drug discovery. Due to the excellent tumor cell growth inhibitory profile and sub-nanomolar potency, Coibamide A (CA), an N-methyl-stabilized depsipeptide isolated from marine cyanobacterium, has been considered as a promising lead compound for cancer treatment. However, the molecular anti-cancer mechanism of the action of CA remains unclear. Here, we showed that CA treatment induced caspase-independent cell death in breast cancer cells. CA treatment also led to severe lysosome defects, which was ascribed to the impaired glycosylation of lysosome membrane protein LAMP1 and LAMP2. As a consequence, the autophagosome-lysosome fusion was blocked upon CA treatment. In addition, we presented evidence that this autophagy defect partially contributed to the CA treatment-induced tumor cell death. Together, our work uncovers a novel mechanism underlying the anti-cancer action of CA, which will promote its further application for cancer therapy.

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.

Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy.

Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

A ratiometric fluorescent probe based on quinoline for monitoring and imaging of Leucine aminopeptidase in liver tumor cells.

Leucine aminopeptidase (LAP) is known as an important potential biomarker for liver malignancy and it is urgent to develop an intuitive and effective method to monitor the activity of LAP in liver cancer. Although, numerous LAP fluorescent probes had been developed, it is still a challenge to detect LAP activity in liver cancer. Herein, combained with the DFT, we reported a novel galactose-appended hepatoma-specific ratiometric fluorescent probe (Gal-QL-Leu) based on quinoline group for imaging and tracing LAP in liver tumor cells. Probe Gal-QL-Leu demonstrated a obvious ratiometric characteristics, better selectivity, good biocompatibility and high sensitivity. Moreover, the selective imaging of LAP in HepG2, HCT116, A549 and HeLa cells had been achieved with probe Gal-QL-Leu, demonstrating good application prospect in the detection of LAP activity in liver tumor cells.

Long non-conding RNA LOXL1-AS1 sponges miR-589-5p to up-regulate CBX5 expression in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a common malignant tumor that seriously endangers people's health. In recent years, long non-coding RNAs (lncRNAs) have been discovered to play vital roles in diverse cancers, including RCC. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) has been found to exert carcinogenic functions in several cancers, but its role and mechanism in RCC have not been investigated. METHODS: qRT-PCR was utilized for testing RNA expression and Western blot for protein expression in RCC tissues or cells. Then, we assessed cell function by conducting a series of functional experiments, such as 5-ethynyl-2'-deoxyuridine staining, colony formation, flow cytometry, JC-1, Western blot and transwell migration experiments. Following, RNA immunoprecipitation, pull down and luciferase reporter experiments were carried out to explore the regulatory mechanisms of LOXL1-AS1 in RCC. RESULTS: LOXL1-AS1 was highly expressed in RCC tissues and cells. Moreover, knockdown of LOXL1-AS1 hampered RCC cell proliferation and migration. Importantly, miR-589-5p that was lowly expressed and worked as a tumor-inhibitor in RCC was found to bind with LOXL1-AS1. Furthermore, chromobox 5 (CBX5) targeted by miR-589-5p could expedite cell proliferation and migration in RCC. Finally, overexpressed CBX5 or inhibited miR-589-5p reversed the repressive impacts of silenced LOXL1-AS1 on RCC malignant phenotypes. CONCLUSIONS: LncRNA LOXL1-AS1 sequestered miR-589-5p to augment CBX5 expression in RCC cells, opening a new way for potential development in RCC treatment.

Chlorotoxin-derived bicyclic peptides for targeted imaging of glioblastomas.

A convenient and efficient strategy was developed for accessing chlorotoxin-derived bicyclic peptide-biomolecule conjugates by cyclizing fully-unprotected linear peptides with a designed tetrafunctional chemical linker. Among these peptides, bicycle-P3 bearing the N-terminal sequence of chlorotoxin shows high tumor selectivity and penetration ability, which is promising for treatment of gliomas.

Drinking Frequency but not Years may be Associated with Lower Urinary Tract Symptoms: Result from a Large Cross-Sectional Survey in Chinese Men.

OBJECTIVE: To evaluate the effect of the drinking frequency and years on lower urinary tract symptoms (LUTS) in a large Chinese male population. METHODS: The current data were obtained from a consecutive series of 3,229 men aged 18-79 who participated in a routine physical examination in Fangchenggang First People's Hospital, Guangxi, China. During a face-to-face interview, the detailed demographic variables about alcohol consumption, potential confounding factors were collected. LUTS were assessed by International Prostate Symptom Score (IPSS) and defined as total LUTS, irritative (IRR) and obstructive (OBS) symptoms, respectively. Multivariate logistic regression analysis was used to evaluate the risk of total LUTS, IRR and OBS symptoms affected by alcohol consumption. RESULTS: The prevalence of moderate to severe LUTS was 8.3% and apparently increased with age (P<0.001). A significant distribution presented in age, alcohol consumption, BMI, cigarette smoking, education attainment and hypertension among different strata of LUTS severity (P<0.05). Men who drank 1-2 times per week were less likely to have OBS symptoms (OR=0.45, 95%CI=0.29-0.70) regardless of age (OR=0.52, 95%CI=0.33-0.82) or multivariate adjusted (OR=0.52, 95%CI=0.33-0.83). Nevertheless, we did not observe a significant negative or positive association presented between drinking years and the risk of total LUTS, OBS and IRR symptoms. CONCLUSION: The current results imply that moderate drinking frequency may be protective against LUTS, and drinking years did not relate to worsening or improving LUTS.

Gene mutation detection of urinary sediment cells for NMIBC early diagnose and prediction of NMIBC relapse after surgery.

Early diagnose of bladder cancer could lead to good prognosis and high 5-year-survival rate. Among bladder cancer, about 75% patients with were nonmuscle-invasive bladder cancer (NMIBC). Patients were painful and easily get infected during bladder cancer diagnosis, which mainly depends on invasive cystoscopy and low-sensitivity urine exfoliation cytology. Meanwhile, relapse after surgery was also becoming the major problem for patients. Exploring noninvasive, high-sensitivity, and painless method is very important and meaningful for NMIBC treatment.Firstly, we found potential related gene mutation sites for NMIBC by searching COSMIC database and related study. Urinary sediment cells of patients both in normal group (patients with benign) and NMIMC group were collected before and after operation for potential gene mutation site detecting. Meanwhile, the urinary sediment cells of relapse patients and good prognosis people in NMIBC group after surgery were also collected for further Gene mutation detection and NMIBC relapse after surgery prediction.Fourteen genes (152 mutation sites) were selected between 95 NMIBC patients and 67 control patients, which were FGFR3, TP53, PIK3CA, and others. Compared with control group, mutation ratio of above 14 genes was higher in NMIBC group. NMIBC diagnose model was established by 5 times cross-validation and had a good effects, which included the all mutation site in FGFR3, TP53, PIK3CA, ARID1A, STAG2, and KTM2D. On the contrary, the relapse rate was 30.5% among 95 patients for about 1.5-year follow-up time. Compared with control group, smoking rate and tumor grade were higher in relapse group. Meanwhile, mutation rate of FGFR3, TP53, PIK3CA, ERBB3, and TSC1 in relapse group were higher than that in normal group. According to the mutation sites of FGFR3, TP53, PIK3CA, and ERBB3 and the combination of urinary sediment cells genetic mutation and relapse status, a predicted model for NMIBC relapse was also established, which had 90% accuracy.The diagnosed NMIBC model (based on FGFR3, TP53, PIK3CA, ARID1A, STAG2, and KTM2D gene mutation) and predicted relapse model (based on FGFR3, TP53, PIK3CA, and ERBB3 gene mutation) possess high accuracy and would be applied in early diagnose and early predicting relapse of patients.

Angiogenesis and bone regeneration by mesenchymal stem cell transplantation with danshen in a rabbit model of avascular necrotic femoral head.

The present study aimed to explore the potential of combined treatment with mesenchymal stem cells (MSCs) and danshen for angiogenesis and bone regeneration in a rabbit model of avascular necrosis of femoral head (ANFH). A rabbit model of ANFH was established using the Shwartzman reaction with methylprednisolone and Escherichia coli endotoxin injection. Magnetic resonance imaging (MRI) and histopathological examination were used to evaluate the rabbit model of ANFH. The rabbits were randomly divided into the danshen group, the MSCs group, the danshen combined with MSCs group and the model group (treated with physiological saline). The expression level of monocyte chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1 (SDF-1) were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression level of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were detected by immunofluorescence and the mRNA expression of BMP-2 and VEGF were detected by RT-PCR. Typical osteonecrosis occurred in the rabbit model of ANFH, which indicated that the model was successfully established. MCP-1 and SDF-1 were significantly increased in the model group compared with the normal group (P<0.05). Following the administration of MSCs and Salvia miltiorrhiza (danshen), MSCs labeled with 5-bromo-2-deoxyuridine were observed to be gathered in the necrotic area. The increased migration of MSCs to the necrotic area may be due to the upregulated expression of the chemokines MCP-1 and SDF-1. ANFH treated with danshen combined with MSCs may promote revascularization by increasing the expression of VEGF and BMP-2 in the femoral head, promoting re-ossification and revascularization. Danshen combined with the transplantation of MSCs may be regarded as a novel therapy for the treatment of ANFH in a clinical setting.

Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation.

Inhibitors and nucleic acid based techniques were two main approaches to interfere with protein signaling and respective cascade in the past. Until recently, a new class of small molecules named proteolysis-targeting chimeras (PROTACs) have emerged. Each contains a target warhead, a linker and an E3 ligand. These bifunctional molecules recruit E3 ligases and target specific proteins for degradation via the ubiquitin (Ub) proteasome system (UPS). The degradation provides several advantages over inhibition in potency, selectivity and drug resistance. Thus, a variety of small molecule PROTACs have been discovered so far. In this review, we summarize the biological mechanism, advantages and recent progress of PROTACs, trying to offer an outlook in development of drugs targeting degradation in future.

CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.

Cyclin-dependent kinases 8 (CDK8) regulates transcriptional process via associating with the mediator complex or phosphorylating transcription factors (TF). Overexpression of CDK8 has been observed in various cancers. It mediates aberrant activation of Wnt/ß-catenin signaling pathway, which is initially recognized and best studied in colorectal cancer (CRC). CDK8 acts as an oncogene and represents a potential target for developing novel CDK8 inhibitors in cancer therapeutics. However, other study has revealed its contrary role. The function of CDK8 is context dependent. Even so, a variety of potent and selective CDK8 inhibitors have been discovered after crystal structures were resolved in two states (active or inactive). In this review, we summarize co-crystal structures, biological mechanisms, dysregulation in cancers and recent progress in the field of CDK8 inhibitors, trying to offer an outlook of CDK8 inhibitors in cancer therapy in future.