Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB.

The MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF-SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion of Srf or Mrtfb, but not Mrtfa, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used fluorescence-activated cell sorting-based hair cell RNA-Seq analysis to investigate the mechanistic underpinnings of the changes observed in Srf and Mrtfb mutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated by Srf and Mrtfb, suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated by Srf and Mrtfb. Exogenous delivery of calponin 2 using Adeno-associated virus transduction in Srf mutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement of Cnn2, as an Srf downstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated by Srf and Mrtfb in hair cells, and also demonstrates the critical role of SRF-CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.

Discovery, Optimization, and Evaluation of Novel N-(Benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive target for cancer therapy. However, identifying potent and selective STAT3 small-molecule inhibitors with drug-like properties remains challenging. Based on a scaffold combination strategy, compounds with a novel N-(benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine scaffold were designed and their inhibition of the interleukin-6 (IL-6)/JAK/STAT3 pathway was tested in HEK-Blue IL-6 reporter cells. After optimization of lead compound 12, compound 40 was identified as a selective STAT3 inhibitor that directly binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. Compound 40 exhibited antiproliferative activities against STAT3-overactivated DU145 (IC50 value = 2.97 µM) and MDA-MB-231 (IC50 value = 3.26 µM) cancer cells and induced cell cycle arrest and apoptosis. In the DU145 xenograft model, compound 40 showed in vivo antitumor efficacy following intraperitoneal administration, with a tumor growth inhibition rate of 65.3% at 50 mg/kg, indicating promise for further development.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

C21 steroids from the roots of Marsdenia tenacissima.

A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C21 steroids (1-16) and isolation of eleven known C21 steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC50 value of 5.2 µM.

Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway.

BACKGROUND: Chlorogenic acid (CHA) has been shown to have substantial biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the pharmacological role of CHA in neuroblastoma has not yet been assessed. Neuroblastoma is a type of cancer that develops in undifferentiated sympathetic ganglion cells. This study aims to assess the antitumor activity of CHA against neuroblastoma and reveal its mechanism of action in cell differentiation. METHODS: Be(2)-M17 and SH-SY5Y neuroblastoma cells were used to confirm the differentiation phenotype. Subcutaneous and orthotopic xenograft mouse models were also used to evaluate the antitumor activity of CHA. Seahorse assays and metabolomic analyses were further performed to investigate the roles of CHA and its target ACAT1 in mitochondrial metabolism. RESULTS: CHA induced the differentiation of Be(2)-M17 and SH-SY5Y neuroblastoma cells in vivo and in vitro. The knockdown of mitochondrial ACAT1, which was inhibited by CHA, also resulted in differentiation characteristics in vivo and in vitro. A metabolomic analysis revealed that thiamine metabolism was involved in the differentiation of neuroblastoma cells. CONCLUSIONS: These results provide evidence that CHA shows good antitumor activity against neuroblastoma via the induction of differentiation, by which the ACAT1-TPK1-PDH pathway is involved. CHA is a potential drug candidate for neuroblastoma therapy.

Artificial intelligence in thyroid ultrasound.

Artificial intelligence (AI), particularly deep learning (DL) algorithms, has demonstrated remarkable progress in image-recognition tasks, enabling the automatic quantitative assessment of complex medical images with increased accuracy and efficiency. AI is widely used and is becoming increasingly popular in the field of ultrasound. The rising incidence of thyroid cancer and the workload of physicians have driven the need to utilize AI to efficiently process thyroid ultrasound images. Therefore, leveraging AI in thyroid cancer ultrasound screening and diagnosis cannot only help radiologists achieve more accurate and efficient imaging diagnosis but also reduce their workload. In this paper, we aim to present a comprehensive overview of the technical knowledge of AI with a focus on traditional machine learning (ML) algorithms and DL algorithms. We will also discuss their clinical applications in the ultrasound imaging of thyroid diseases, particularly in differentiating between benign and malignant nodules and predicting cervical lymph node metastasis in thyroid cancer. Finally, we will conclude that AI technology holds great promise for improving the accuracy of thyroid disease ultrasound diagnosis and discuss the potential prospects of AI in this field.

Synthesis and Bioactivity Evaluation of Nepetaefolin F and Its Analogues.

Nepetaefolin F (5), an abietane diterpenoid, showed significant inhibitory activity against human cancer cells in vitro with an IC50 value of 6.3 µM. The syntheses of nepetaefolin F and its analogues are presented herein. The cytotoxicity against various cancer cell lines was evaluated; notably, the cyclopropanecarboxylate ester 42 displayed significant antitumor activity against MGC 803 cells with an IC50 value of 20.9 µM. Further studies revealed that 42 could upregulate the expression of p62, microtubule-associated protein 1 light-chain 3 ß (LC3 B-I), cleaved caspase-3, and cleaved caspase-9 and downregulate the expression of Beclin-1 and LC3B-II. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 42 could modulate multiple signaling pathways, especially for peroxisome proliferator-activated receptor (PPAR) and AMP-activated protein kinase (AMPK), which are closely related to autophagy. These results suggested that compound 42 is a promising lead by inhibiting cell proliferation and autophagy, as inducing cell apoptosis in MGC 803 cells.

Changes of gut microbiota and tricarboxylic acid metabolites may be helpful in early diagnosis of necrotizing enterocolitis: A pilot study.

Purpose: We aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations. Methods: Thirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data. Results: There was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively. Conclusion: Decreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.

Corrigendum: Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis.

[This corrects the article DOI: 10.3389/fonc.2023.1007464.].

GSH-Activatable Aggregation-Induced Emission Cationic Lipid for Efficient Gene Delivery.

The key to gene therapy is the design of biocompatible and efficient delivery systems. In this work, a glutathione (GSH)-activated aggregation-induced-emission (AIE) cationic amphiphilic lipid, termed QM-SS-KK, was prepared for nonviral gene delivery. QM-SS-KK was composed of a hydrophilic biocompatible lysine tripeptide headgroup, a GSH-triggered disulfide linkage, and a hydrophobic AIE fluorophore QM-OH (QM: quinoline-malononitrile) tail. The peptide moiety could not only efficiently compact DNA but also well modulate the dispersion properties of QM-SS-KK, leading to the fluorescence-off state before GSH treatment. The cleavage of disulfide in QM-SS-KK by GSH generated AIE signals in situ with a tracking ability. The liposomes consisted of QM-SS-KK, and 1,2-dioleoylphosphatidylethanolamine (DOPE) (QM-SS-KK/DOPE) delivered plasmid DNAs (pDNAs) into cells with high efficiency. In particular, QM-SS-KK/DOPE had an enhanced transfection efficiency (TE) in the presence of 10% serum, which was two times higher than that of the commercial transfection agent PEI25K. These results highlighted the great potential of peptide and QM-based fluorescence AIE lipids for gene delivery applications.

Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis.

Purpose: The aim of this study was to investigate the diagnostic efficacy of Acoustic Radiation Force Impulse (ARFI) for benign and malignant thyroid nodules in the presence and absence of non-papillary thyroid cancer (NPTC) and to determine the cut-off values of Shear Wave Velocity (SWV) for the highest diagnostic efficacy of Virtual Touch Quantification (VTQ) and Virtual Touch Tissue Imaging and Quantification (VTIQ). Methods: The diagnostic accuracy of ARFI for benign and malignant thyroid nodules was assessed by pooling sensitivity, specificity and area under the curve (AUC) in each group in the presence and absence of both non-papillary thyroid glands, using histology and cytology as the gold standard. All included studies were divided into two groups according to VTQ and VTIQ, and each group was ranked according to the magnitude of the SWV cutoff value to determine the SWV cutoff interval with the highest diagnostic efficacy for VTQ and VTIQ. Results: A total of 57 studies were collected on the evaluation of ARFI for the diagnosis of benign and malignant thyroid nodules. The results showed that the presence of non-papillary thyroid carcinoma led to differences in the specificity of VTIQ for the identification of benign and malignant thyroid nodules, and the differences were statistically significant. In addition, the diagnostic efficacy of VTQ was best when the cutoff value of SWV was in the interval of 2.48-2.55 m/s, and the diagnostic efficacy of VTIQ was best when the cutoff value of SWV was in the interval of 3.01-3.15 m/s. Conclusion: VTQ and VTIQ have a high diagnostic value for benign and malignant thyroid nodules; however, when the malignant nodules in the study contain non-papillary thyroid carcinoma occupying the thyroid gland, the findings should be viewed in a comprehensive manner.

New compounds from Patrinia villosa Juss. and their anti-inflammatory activities.

Five new iridoids, patriscabioins M-Q and a new monoterpene, eldanolide acid, together with three known iridoids, were isolated from the 95% aqueous EtOH extract whole plants of Patrinia villosa Juss. The structures were established by a variety of spectroscopic analysis, such as IR, 1 D and 2 D NMR spectra, MS, ECD and X-ray diffraction data. Bioactivity screening revealed the inhibitory effects on nitric oxide (NO) production of them in lipopolysaccharide-activated RAW264.7 cells with Aminoguanidine Hydrochloride as the positive control. Among them, patriscabioin M (1), patriscabioin N (2), patriscabioin P (4), patriscabioin Q (5), 8,9-didehydro-7-hydroxydolichodia (7) were found to markedly reduce LPS-induced NO production in murine macrophage cells with IC50 values of 18.14, 18.93, 22.00, 13.64, 26.48 µM, respectively.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease.

There are many documented sex differences in the clinical course, symptom expression profile, and treatment response of Parkinson's disease, creating additional challenges for patient management. Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson's disease, the effects of sex on treatment outcome are still unclear. The aim of this retrospective observational study, was to examine sex differences in motor symptoms, non-motor symptoms, and quality of life after subthalamic nucleus deep brain stimulation. Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation aged 63.00 ± 8.01 years (55 men and 35 women). Outcomes of clinical evaluations were compared between sexes via a Student's t-test and within sex via a paired-sample t-test, and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex. We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation. Restless legs syndrome was alleviated to a greater extent in men than in women. Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation. Furthermore, Hoehn-Yahr stage was positively correlated with the treatment response in men, while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women. In conclusion, women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms, non-motor symptoms, and quality of life. We found sex-specific factors, i.e., Hoehn-Yahr stage and levodopa equivalent dose, that were related to motor improvements. These findings may help to guide subthalamic nucleus deep brain stimulation patient selection, prognosis, and stimulation programming for optimal therapeutic efficacy in Parkinson's disease.

Succinate aggravates intestinal injury in mice with necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal disorder that predominantly threatens preterm newborns. Succinate is an emerging metabolic signaling molecule that was recently studied in relation to the regulation of intestinal immunity and homeostasis. We aimed to investigate the relationship between NEC and gut luminal succinate and preliminarily explored the effect of succinate on NEC pathogenesis. Methods: Fecal samples from human neonates and mouse pups were analyzed by HPLC - MS/MS and 16S rRNA gene sequencing. C57BL/6 mice were randomly divided into four groups: control, NEC, Lsuc, and Hsuc. The mortality, weight gain, and intestinal pathological changes in four mouse groups were observed. Inflammatory cytokines and markers of macrophages were identified by quantitative real-time PCR. Succinate receptor 1 (SUCNR1) localization was visualized by immunohistochemistry. The protein levels of SUCNR1 and hypoxia-inducible factor 1a (HIF-1a) were quantified by western blotting. Results: The levels of succinate in feces from NEC patients were higher than those in feces from non-NEC patients (P <0.05). In the murine models, succinate levels in intestinal content samples were also higher in the NEC group than in the control group (P <0.05). The change in succinate level was closely related to intestinal flora composition. In samples from human neonates, relative to the control group, the NEC group showed a higher abundance of Enterobacteriaceae and a lower abundance of Lactobacillaceae and Lactobacillus (P <0.05). In the murine models, relative to the control group, increased abundance was observed for Clostridiaceae, Enterococcaceae, Clostridium_sensu_stricto_1, and Enterococcus, whereas decreased abundance was observed for Lactobacillaceae and Lactobacillus (P <0.05). Increased succinate levels prevented mice from gaining weight, damaged their intestines, and increased their mortality; upregulated the gene expression of interleukin-1ß (IL-1ß), IL-6, IL-18 and tumor necrosis factor (TNF); and downregulated the gene expression of IL-10 and transforming growth factor (TGF)-ß. Exogenous succinic acid increased inducible nitric oxide synthase (iNOS) gene expression but decreased Arginase-1 (Arg1) gene expression; and increased the protein expression of SUCNR1 and HIF-1a. Conclusion: Succinate plays an important role in the development of necrotizing enterocolitis severity, and the activation of the HIF-1a signaling pathway may lead to disease progression.

Clinical characteristics of smoking-related chronic pancreatitis.

Objective: The pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking. Design: Patients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively. Results: A total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea. Conclusion: The clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

Transcriptome Sequencing Reveal That Rno-Rsf1_0012 Participates in Levodopa-Induced Dyskinesia in Parkinson's Disease Rats via Binding to Rno-mir-298-5p.

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson's disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p < 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID.

Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study.

Background: Dysbacteriosis is thought to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). We aimed to identify new biomarkers among gut microbiota and short-chain fatty acids (SCFAs) for the early prediction of NEC. Materials and methods: Thirty-four preterm infants with gestational ages of ≤ 34 weeks who developed gastrointestinal symptoms were divided into the NEC group (n = 17) and non-NEC group (n = 17). In the NEC group, the gut microbiota and SCFAs in feces were assessed when the infants were enrolled (Group P) and when they were diagnosed with NEC (Group N). In the non-NEC group, samples were assessed when the infants were enrolled (Group C). Results: The Ace and Chao1 indices were higher in Group P than in Group C (P < 0.05), and there was no difference between Groups C and N or between Groups P and N (P > 0.05). There was no significant difference in the Simpson and Shannon indices among Groups C, P and N (P > 0.05). The four main phyla showed no differences (P > 0.05) in composition, while at the genus level, compared with Group C, in Group P, Clostridioides, Blautia and Clostridium_sensu_stricto_1 were increased, while Lactobacillus and Bifidobacterium were decreased (P < 0.05). At the species level, Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium animals subsp. lactis decreased (P < 0.05). In Group N, at the genus level, Stenotrophomonas, Streptococcus and Prevotella increased (P < 0.05). Compared with those in Group C, the levels of acetic acid, propanoic acid and butyric acid decreased significantly in Groups P and N (P < 0.05), and the areas under the curves (AUCs) of these three SCFAs between groups C and P were 0.73, 0.70, and 0.68, respectively. Conclusion: The increase in Streptococcus salivarius and Rothia mucilaginosa and decrease in Bifidobacterium_animals_subsp._lactis, as well as the decrease in acetic, propionic and butyric acids, may help in the early prediction of NEC.

(+)-Isocryptotanshinone derivatives and its simplified analogs as STAT3 signaling pathway inhibitors.

Isocryptotanshinone (ICTS), a natural product with potential signal transducer and activator of transcription-3 (STAT3) signaling pathway inhibitory activity, shows significant inhibitory activity against several tumors. In this study, a series of ICTS derivatives and simplified analogs containing a 1, 4-naphthoquinone core was designed, synthesized, and evaluated. The results demonstrated that most target compounds were potent STAT3 signaling pathway inhibitors based on their mechanism of inhibition of STAT3 phosphorylation. Moreover, based on the obtained data, the structure-activity relationship (SAR) was rationally deduced. Simultaneously, molecular docking of the compound 16r suggested its possible interaction mode with STAT3. To further verify anticancer activity, all target compounds were tested using HCT116, HepG2, MCF-7, A549, and U251 cell lines. Interestingly, compared with different tumor cell lines, the HCT-116 cell line was determined to be the most sensitive. Furthermore, compounds 21e, 16r, 28a, and 16e showed a dose-dependent inhibition of the growth of HCT116 cells. Thus, the SAR of ICTS derivatives and its simplified analogs was determined, and some of them were discovered to be potential anticancer candidates owing to their ability to inhibit the STAT3 signaling pathway.

Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity.

Polycyclic aromatic systems have been considered good biological probes, but some may also be good scaffolds for drug development. In this study, a series of benzobis(imidazole) derivatives were identified as STAT3 signal inhibitors, among which compound 24 showed significant inhibition of IL-6 induced JAK/STAT3 signalling pathway activation. Moreover, 24 inhibited cancer cell growth and migration, and induced cell apoptosis as well as cycle arrest in human hepatocellular carcinoma cells (HepG2) and oesophageal carcinoma cells (EC109). Compound 24 also displayed obvious antitumor activity in a mouse HepG2 cell xenograft tumor model without affecting the body weight. These results confirmed that 24 was a potential STAT3 signal inhibitor with certain antitumor activity.