Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Construction of an Exercise Intervention Program for Patients with Sarcopenic Obesity: A Delphi Method Study.

Purpose: Construct an exercise intervention program for patients with sarcopenic obesity. Material and Methods: Based on the COM-B theoretical model and evidence-based principles, the program was constructed using qualitative methods of literature analysis and Delphi method. The Delphi panel consisted of 15 experts from the fields of clinical medicine, rehabilitation medicine, medical technology, and nursing. Results: Fifteen experts were consulted, and the consultation recovery rate was 100%; the authority coefficient of the 1st round was 0.83, with coefficients of variation ranging from 0.00 to 0.27, and importance scores ranging from (4.13±1.13) to (5±0); the authority coefficient of the 2nd round was 0.82, with coefficients of variation ranging from 0.00 to 0.20, and importance scores ranging from (4.53±0.64) to (5±0); Kendall's harmony coefficient was 0.102, 0.115, respectively, and the differences were statistically significant(P < 0.05). The constructed exercise intervention program for patients with sarcopenic obesity included 4 primary indicators, 12 secondary indicators, and 28 tertiary indicators. Conclusion: The constructed exercise intervention program for patients with sarcopenic obesity is scientific, feasible and generalizable, and can provide useful reference for related personnel to develop exercise programs for patients with sarcopenic obesity.

Discovery of Highly Potent and Efficient CBP/p300 Degraders with Strong In Vivo Antitumor Activity.

The transcriptional coactivator cAMP response element binding protein (CREB)-binding protein (CBP) and its homologue p300 have emerged as attractive therapeutic targets for human cancers such as acute myeloid leukemia (AML). Herein, we report the design, synthesis, and biological evaluation of a series of cereblon (CRBN)-recruiting CBP/p300 proteolysis targeting chimeras (PROTACs) based on the inhibitor CCS1477. The representative compounds 14g (XYD190) and 14h (XYD198) potently inhibited the growth of AML cells with low nanomolar IC50 values and effectively degraded CBP and p300 proteins in a concentration- and time-dependent manner. Mechanistic studies confirmed that 14g and 14h can selectively bind to CBP/p300 bromodomains and induce CBP and p300 degradation in bromodomain family proteins in a CRBN- and proteasome-dependent manner. 14g and 14h displayed remarkable antitumor efficacy in the MV4;11 xenograft model (TGI = 88% and 93%, respectively). Our findings demonstrated that 14g and 14h are useful lead compounds and deserve further optimization and activity evaluation for the treatment of human cancers.

JAK3/STAT5 signaling-triggered upregulation of PIK3CD contributes to gastric carcinoma development.

Gastric cancer (GC) is one of the most common solid cancers with high incidence and mortality worldwide. Chronic gastritis and consequent inflammatory microenvironment is known as a major cause leading to gastric carcinogenesis. Here we report that PIK3CD that encodes p110δ, a catalytic subunit of the class IA PI3Ks, is overexpressed and tumorigenic in GC and associated with tumor inflammatory microenvironment. By investigating the data from TCGA database and our immunohistochemical staining and quantitative real-time PCR results from clinical samples, we found PIK3CD exhibits higher expression level in GC tissues compared with adjacent non-tumorous stomach tissues. Genetic silencing of PIK3CD in GC cells retards proliferation and migration in vitro and tumorigenicity and metastasis in vivo. In contrast, enhanced expression of PIK3CD promotes these phenotypes in vitro. Furthermore, pharmacological inhibition of PIK3CD could reduce GC cell viability and colony formation capacities. More importantly, we reveal a relevant mechanism that PIK3CD, but not PIK3CA and PIK3CB, is transcriptionally regulated by the pro-inflammatory IL2/JAK3/STAT5 axis and tumor-infiltrating immune cells such as lymphocytes. These observations may setup a new crosstalk between tumor inflammatory microenvironment, IL2/JAK3/STAT5 signaling and PI3K/AKT signaling. Targeting PIK3CD may be a promising therapy strategy for GC.

SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis.

PIK3CB, one of catalytic subunits of PI3Ks kinase family, is implicated in several cellular processes such as cell growth, proliferation, mobility and neoplastic transformation. Its abnormal expression has been found in several human cancer types. However, the regulation pattern and function of PIK3CB in gastric cancer (GC) are still unclear. Here, we demonstrated that PIK3CB and SP1 (special protein 1) were both upregulated in GC samples compared to adjacent non-cancerous stomach tissues at mRNA and protein levels. The expression of the two genes also displayed a significant positive correlation in GC samples. Dual-luciferase assays and chromatin immunoprecipitation (ChIP) assays revealed that SP1 could bind to the -771~-605 region of the promoter of PIK3CB and enhance transcription. Furthermore, we discovered that SP1 induced AKT activation through PIK3CB and accelerated GC cell proliferation and migration in a PIK3CB/AKT signaling dependent manner. TGX-221, a PIK3CB-selective inhibitor, which can block this signaling transduction pathway, was found to inhibit the growth of GC cells and induce apoptosis in vitro, implying that it may act as a potential development agent for GC. These collective findings provide a new insight into PI3K/AKT signaling that SP1 may function as an upstream factor on PI3K, forming a new signaling axis to promote the progression of GC or other malignancies.

Optimization of the synthesis of BET BD2 selective inhibitor XY153.

XY153 is a promising BET BD2 inhibitor with an IC50 value of 0.79 nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains. However, the reported synthesis route of XY153 and its derivatives are extremely poor-yielding. After the synthesis of three key fragments, XY153 can only be obtained with a yield of 1.3 % in the original four-step reaction. In this study, we reported a three-step alternative route in the synthesis process of XY153. The reaction conditions for this route were thoroughly investigated and optimized, resulting in a significantly improved yield of 61.5 %. This efficient synthesis route establishes a robust chemical foundation for the rapid synthesis of XY153 derivatives as BET BD2 inhibitors in the near future.

A Ratio Fluorescence Method Based on Dual Emissive Copper Nanoclusters for the Detection of Vanillin.

In this study, a novel double-emission fluorescence probe at 340 and 400 nm was synthesized by one-pot method using phenylalanine (Phe) and ascorbic acid (AA) as stabilizing and reducing agents. It was found that the fluorescence intensity of the probe at 400 nm could be controlled by controlling the temperature within a certain range, and the ratio of double-emission fluorescence probe could be further regulated. Under the optimal conditions, the fluorescence intensity at 340 nm decreased significantly, while it only showed a slight decrease at 400 nm, which constituted the ratio fluorescence probe. The synthesized fluorescence probe showed good linearity in the range of 0.2-32 µM, and its detection limit was 63.4 nM. Moreover, the method was successfully employed to determine VA in vanilla drink and perfumes, and corresponding results were consistent with those of HPLC.

The Fibrosis-5 Index Predicts Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

This study aimed to evaluate the fibrosis-5 (FIB-5) index as a marker of liver fibrosis for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 406 STEMI patients were enrolled in the study. Over an average follow-up of 27 months, 143 of the patients developed MACE. The patients were subgrouped into tertiles based on the FIB-5 index and Kaplan-Meier survival (MACE-free) curves were plotted, showing statistically significant differences (log-rank test, P < .001). In the adjusted Cox regression model, the hazard ratio (HR) of MACE was 1.95 (95% CI 1.21-3.13; P = .006) in tertile 3 and 0.98 (95% CI 0.97-1.00; P = .013) for per unit increase in the FIB-5 index. The area under the curve (AUC) of the FIB-5 index predicting the occurrence of MACE in STEMI patients after PCI was 0.645 (95% CI 0.590-0.701; P < .001). Low FIB-5 may be a useful predictor of MACE in STEMI patients undergoing PCI.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Discovery of a potent and selective CBP bromodomain inhibitor (Y08262) for treating acute myeloid leukemia.

The bromodomain of CREB (cyclic-AMP response element binding protein) binding protein (CBP) is an epigenetic "reader" and plays a key role in transcriptional regulation. CBP bromodomain is considered to be a promising therapeutic target for acute myeloid leukemia (AML). Herein, we report the discovery of a series of 1-(indolizin-3-yl)ethan-1-one derivatives as potent, and selective CBP bromodomain inhibitors focused on improving cellular potency. One of the most promising compounds, 7e (Y08262), inhibits the CBP bromodomain at the nanomolar level (IC50 = 73.1 nM) with remarkable selectivity. In addition, the new inhibitor also displays potent inhibitory activities in AML cell lines. Collectively, this study provides a new lead compound for further validation of CBP bromodomain as a molecular target for AML drug development.

Alterations in urinary microbiota composition in urolithiasis patients: insights from 16S rRNA gene sequencing.

Objectives: To investigate the urinary microbiota composition in urolithiasis patients compared to healthy controls and to identify potential microbial markers and their association with clinical parameters. Methods: A total of 66 samples, comprising 45 from urolithiasis patients and 21 from healthy controls, were analyzed. 16S rRNA gene sequencing was employed to determine the microbiota composition. Various statistical and bioinformatics tools, including ANOVA, PCoA, and LEfSe, were utilized to analyze the sequencing data and identify significant differences in microbial abundance. Results: No significant demographic differences were observed between the two groups. Post-quality control, clean tags ranged from 60,979 to 68,736. Significant differences in α-diversity were observed between the two groups. ß-diversity analysis revealed distinct clustering of the urinary microbiota in urolithiasis patients and controls. Notably, Ruminococcaceae was predominant in urolithiasis samples, while Proteobacteria was more prevalent in healthy samples. Lactobacillus was significantly overrepresented in samples from healthy females. Conclusion: The urinary microbiota composition in urolithiasis patients is distinct from that of healthy controls. Specific microbial taxa, such as Ruminococcaceae and Proteobacteria, could serve as potential biomarkers for urolithiasis. The findings pave the way for further exploration of the role of microbiota in urolithiasis and the development of microbiome-based therapeutic strategies.

Sensitive Detections of Sodium Dichloroisocyanurate and Rosmarinic Acid by Polyvinylpyrrolidone Coated Copper Nanoclusters.

In this article, the water-soluble blue-light-emitting copper nanoclusters (CuNCs) were prepared by polyvinylpyrrolidone (PVP) and ascorbic acid as templating and reducing agents, respectively. The optimization of synthesis conditions of PVP-CuNCs were studied and analyzed. And the quantum yield of the PVP-CuNCs was calculated to be 14.97%. It had good specificity and exceptionally sensitive detection for sodium dichloroisocyanurate (DCCNa)/rosmarinic acid (RA), with a linear response range of 0.030-2.400/0.030-0.900 µM and corresponding LOD value of 10.766/8.985 nM. Moreover, the fluorescent reaction mechanisms of the PVP-CuNCs-DCCNa and PVP-CuNCs-DCCNa-RA systems were discussed, and the sensing probe could be effectively used for the assays of DCCNa and RA in genuine samples, whose results were acceptable.

Characteristics and risk of interstitial lung disease in dermatomyositis and polymyositis: a retrospective cohort study in Japan.

Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42-20.59) for dermatomyositis and 5.39 (95% CI 4.43-6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18-3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.

Impact of plaque characteristics on percutaneous coronary intervention-related microvascular dysfunction: insights from angiographic microvascular resistance and intravascular ultrasound.

Background: The correlation between percutaneous coronary intervention (PCI)-related microvascular dysfunction (MVD) and plaque characteristics remains unclear. To investigate this correlation and its prognosis, we assessed changes in MVD by angiographic microvascular resistance (AMR) and intracoronary ultrasound scans after PCI. Methods: We conducted a retrospective study that enrolled 250 patients with coronary artery disease between July 2016 and December 2018. We collected demographic characteristics, laboratory tests, coronary angiography (CAG) and intracoronary ultrasound findings. We calculated quantitative flow ratio (QFR) and AMR by CAG. The endpoint was vessel-oriented composite outcomes (VOCOs). Results: After 47 exclusions, we divided 203 cases into a deteriorated group (n=139) and an improved group (n=64) based on AMR change after PCI. Compared with the improved group, the deteriorated group had smaller lumen area [3.03 (interquartile range, 2.20-3.91) vs. 3.55 mm2 (interquartile range, 2.45-4.57), P=0.033], higher plaque burden [78.92% (interquartile range, 73.95-82.61%) vs. 71.93% (interquartile range, 62.70-77.51%), P<0.001], and higher proportion of lipidic components (13.86%±4.67% vs. 11.78%±4.41%, P=0.024). Of 186 patients who completed 4.81±1.55 years follow-up, 56 developed VOCOs. Receiver-operating characteristic (ROC) curve analysis showed post-PCI AMR and VOCOs correlation (area under the curve: 0.729, P<0.001). Multivariate regression analysis showed post-PCI AMR >285 mmHg·s/m correlated with adverse outcome (hazard ratio =4.350; 95% confidence interval: 1.95-9.703; P<0.001). Conclusions: Intravascular ultrasound (IVUS) imaging and AMR revealed an association of post-PCI MVD with a smaller lumen area, more severe plaque burden, and a higher percentage of lipidic components. Post-PCI MVD was an independent risk factor for poor prognosis.

Effects of non-pharmacological interventions on patients with sarcopenic obesity: A meta-analysis.

OBJECTIVE: Systematic evaluation of the improvement effect of non-pharmacological intervention on patients with sarcopenic obesity. METHODS: Wanfang, VIP, China National Knowledge Infrastructure (CNKI), SinoMed, Web of Science, Cochrane Library, PubMed, and Embase databases were searched systematically for randomized controlled trials (RCTS) and experimental studies of non-pharmacological interventions on patients with sarcopenic obesity. The retrieval period was from the establishment of the databases to October 31, 2022. Meta-analysis was conducted using RevMan 5.4. RESULTS: A total of 18 studies involving 1,109 patients were included. Meta-analysis results showed that non-pharmacological interventions improved patients' body weight [mean difference, MD = -2.74, 95% CI (-4.79, -0.70), P = 0.009], body fat percentage [MD = -0.67, 95% CI (-0.96, -0.38), P<0.00001], grip strength [MD = 1.29, 95% CI (0.81, 1.77), P<0.00001], gait speed [MD = 0.05, 95% CI (0.03, 0.07), P<0.00001], and knee extension strength [MD = 2.56, 95% CI (1.30, 3.82), P<0.0001]. CONCLUSIONS: Non-pharmacological interventions can effectively improve the clinical symptoms and signs of patients with sarcopenic obesity. Dissemination of this information will be therapeutically useful. TRIAL REGISTRATION: Registration. The PROSPERO No. is CRD42023403341.

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis.

OBJECTIVE: To assess S-1 and 5-fluorouracil (5-FU)-related adverse events in patients with advanced gastric cancer and provide focused health care approaches to improve patient compliance and quality of survival. METHODS: The PubMed, Web of Science, Medline, Cochrane Library, EMbase, SinoMed, Wan Fang Data, CNKI, and VIP databases were searched, and relevant literature was screened from the database construction date through March 31, 2023. Review Manager 5.4.1 and Stata 12.0 were used to analyze the data and GRADEpro was used to assess the quality of the literature. Relative risk ratio (RR) and a 95% confidence interval (CI) were employed as markers to compare adverse events due to S-1 vs 5-FU. RESULTS: Eight randomized controlled trials (RCT) were included, which contained 3,455 patients. The S-1 group had 1,804 patients, and the 5-FU group had 1,651 patients. There were 17 recorded adverse events in total. Stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia were more common in the 5-FU group than in the S-1 group (P < 0.001). No significant difference was observed between S-1 and 5-FU for other adverse events. CONCLUSIONS: Although both S-1 and 5-FU cause a variety of side effects, 5-FU resulted in a higher incidence of stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia than S-1. Medical professionals should closely monitor the occurrence of adverse drug events and provide timely, rational guidance and nursing care to improve patient compliance and quality of life.

Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.

The tumor microenvironment (TME) is a crucial driving factor for tumor progression and it can hinder the body's immune response by altering the metabolic activity of immune cells. Both tumor and immune cells maintain their proliferative characteristics and physiological functions through transporter-mediated regulation of nutrient acquisition and metabolite efflux. Transporters also play an important role in modulating immune responses in the TME. In this review, we outline the metabolic characteristics of the TME and systematically elaborate on the effects of abundant metabolites on immune cell function and transporter expression. We also discuss the mechanism of tumor immune escape due to transporter dysfunction. Finally, we introduce some transporter-targeted antitumor therapeutic strategies, with the aim of providing new insights into the development of antitumor drugs and rational drug usage for clinical cancer therapy.

Investigating the Correlation between Serum Amyloid A and Infarct-Related Artery Patency Prior to Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction Patients.

Serum amyloid A (SAA) is a cardiovascular risk factor and may serve as a predictor of infarct-related artery (IRA) patency in patients with ST-segment elevation myocardial infarction (STEMI). We measured SAA levels in STEMI patients who underwent percutaneous coronary intervention (PCI) and investigated their association with IRA patency. According to the Thrombolysis in Myocardial Infarction (TIMI) flow grade, 363 STEMI patients undergoing PCI in our hospital were divided into an occlusion group (TIMI 0-2) and a patency group (TIMI 3). The SAA level before PCI was significantly higher in STEMI patients with IRA occluded than in those with patent ones. At a cutoff value of 36.9 mg/L, SAA had a sensitivity of 63.0% and a specificity of 90.6% (area under the ROC curve [AUC] = .833, 95% CI: .793-.873, P < .001). Multivariate logistic regression analysis showed that SAA was an independent predictor of IRA patency in STEMI patients before PCI (odds ratio [OR] = 1.041, 95% CI: 1.020-1.062, P < .001). SAA can be used as a potential predictor of IRA patency in STEMI patients before PCI.

Species Identification of Caviar Based on Multiple DNA Barcoding.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Heterogeneity and spillover effects of carbon emission trading on green innovation.

The massive emission of greenhouse gases poses a serious threat to the ecological environment. In this context, the relevant effects of the carbon emission trading (CET) market, which promotes greenhouse gas emission reduction by market means, have been widely investigated. Taking the China's CET pilot as a research target, the heterogeneity and spillover effects of CET on green innovation are explored by using the sample data of 279 prefecture-level cities in China from 2008 to 2019. The results are as follows. First, on the whole, CET significantly promotes strategic green innovation, but it has no significant effect on substantive green innovation. Second, the green innovation effect of CET varies with the level of green innovation, and the heterogeneous effects of green innovation are also reflected in different degrees of marketization, fiscal decentralization and government environmental concern. Third, CET has a positive spillover effect on green innovation, and the spillover effect is more significant than the direct effect, accounting for 74.8% of the total effect. Finally, some corresponding policy suggestions are put forward according to the above research conclusions.