Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Brain structural covariances in the ageing brain in the UK Biobank.

The morphologic properties of brain regions co-vary or correlate with each other. Here we investigated the structural covariances of cortical thickness and subcortical volumes in the ageing brain, along with their associations with age and cognition, using cross-sectional data from the UK Biobank (N = 42,075, aged 45-83 years, 53% female). As the structural covariance should be estimated in a group of participants, all participants were divided into 84 non-overlapping, equal-sized age groups ranging from the youngest to the oldest. We examined 84 cortical thickness covariances and subcortical covariances. Our findings include: (1) there were significant differences in the variability of structural covariance in the ageing process, including an increased variance, and a decreased entropy. (2) significant enrichment in pairwise correlations between brain regions within the occipital lobe was observed in all age groups; (3) structural covariance in older age, especially after the age of around 64, was significantly different from that in the youngest group (median age 48 years); (4) sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations showed significant associations with age. These trends varied, with some correlations strengthening, some weakening, and some reversing in direction with advancing age. Additionally, as ageing was associated with cognitive decline, most of the correlations with cognition displayed an opposite trend compared to age associated patterns of correlations.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

Preventing of nonunion in congenital pseudarthrosis of the tibia cases of Crawford Type I and II through the use of allograft bypass and a brace: Midterm findings.

Background: Congenital pseudarthrosis of the tibia is a limb deformity, which can be distressing for the affected patients and the pediatric orthopedic surgeons involved. We hypothesized that the modified McFarland procedure would avoid fractures and even have a corrective effect on the affected tibia in congenital pseudarthrosis of the tibia patients. Toward this end, we evaluated the midterm results of treating congenital pseudarthrosis of the tibia patients of Crawford Type I and II with allograft bypass combined with long-term bracing. Methods: This study retrospectively evaluated 7 patients with congenital pseudarthrosis of the tibia who were treated with allograft bypass combined with long-term bracing between 2009 and 2018. The median follow-up was 7.0 years (range 3.8-10.0 years). The medical records and radiographs were reviewed for demographic data, clinical characteristics, outcomes, and complications. Results: At the time of the last follow-up, all allografts revealed complete consolidation in the patients' tibiae at both ends. All patients presented no functional restriction of the lower limbs and no amputation or non-union has occurred. Most of the obvious deformities of the tibia diaphysis or ankle joint were corrected. Two complications occurred that required successful revision surgery. Conclusion: In this series of seven congenital pseudarthrosis of the tibia patients, the allograft bypass technique showed satisfactory midterm results and validated our hypothesis. For congenital pseudarthrosis of the tibia patients of Crawford Type I and II, this procedure combined with long-term bracing, which involves the affected leg only, can delay or possibly prevent fractures, decrease tibial malalignment, and preserve leg length. Level of evidence: level IV.

Reactivating Hippo by drug compounds to suppress gastric cancer and enhance chemotherapy sensitivity.

The Hippo signaling pathway plays an essential role in organ size control and tumorigenesis. Loss of Hippo signal and hyper-activation of the downstream oncogenic YAP signaling are commonly observed in various types of cancers. We previously identified STRN3-containing PP2A phosphatase as a negative regulator of MST1/2 kinases (i.e., Hippo) in gastric cancer (GC), opening the possibility of selectively targeting the PP2Aa-STRN3-MST1/2 axis to recover Hippo signaling against cancer. Here, we further discovered 1) disulfiram (DSF), an FDA-approved drug, which can similarly block the binding of STRN3 to PP2A core enzyme and 2) CX-6258 (CX), a chemical inhibitor, that can disrupt the interaction between STRN3 and MST1/2, both allowing reactivation of Hippo activity to inhibit GC. More importantly, we found these two compounds, via an MST1/2 kinase-dependent manner, inhibit DNA repair to sensitize GC towards chemotherapy. In addition, we identified thiram, a structural analog of DSF, can function similarly to inhibit cancer cell proliferation or enhance chemotherapy sensitivity. Interestingly, inclusion of copper ion enhanced such effects of DSF and thiram on GC treatment. Overall, this work demonstrated that pharmacological targeting of the PP2Aa-STRN3-MST1/2 axis by drug compounds can potently recover Hippo signal for tumor treatment.

Effects of different fertilization practices on maize yield, soil nutrients, soil moisture, and water use efficiency in northern China based on a meta-analysis.

The application of fertilizer to ensure the steady improvement of crop yield has become the main means of agricultural production. However, it remains to be determined whether fertilization practices with different combinations of nitrogen (N), phosphorus (P), potassium (K), and organic (O) fertilizers play a positive role in the sustainability of maize yield and the soil in which it is grown. Therefore,this meta-analysis extracted 2663 data points from 76 studies to systematically analyze and explore the effects of different fertilization measures on maize yield, soil nutrients, water content and water use efficiency (WUE) in northern China. Articles addressing this topic showed that fertilization effectively increased the soil nutrient content and maize yield. The soil organic matter (SOM) increased by 2.36 (N)-55.38% (NPO), total nitrogen content increased by 6.10 (N)-56.39% (NPO), available phosphorus content increased by 17.12 (N)-474.74% (NPO), and available potassium content changed by - 2.90 (NP)-64.40% (NPO). Soil moisture increased by 3.59% under a single organic fertilizer application and decreased by 4.27-13.40% under the other treatments. Compared with no fertilization, the yield increase of fertilized maize reached 11.65-220.42%. NP, NPK and NPKO contributed the most to increased yield in lithological, black and fluvo-aquic soils, respectively. The effects of different fertilization practices on maize yield varied in response to the same meteorological factors. The WUE increased from 9.51 to 160.72%. In conclusion, rational fertilization can improve the soil nutrient content and increase maize yield. The combined application of chemical and organic fertilizer showed the greatest increase in yield and WUE. Organic fertilizer application alone increased soil moisture. Our results provide a theoretical basis for fertilizer application and for improving the soil structure for maize cultivation in northern China.

RAB5A in triple-negative breast cancer: a critical role in macrophage reshaping in an exosomal miR-21-dependent manner.

Breast cancer is the leading cause of cancer-related deaths in females, and triple-negative breast cancer (TNBC) is characterized as one of the main subtypes of breast cancer, with poor prognosis and limited treatments. Investigating the molecular basis or discovering relevant oncogenes will greatly help in developing effective targeted therapies. In this study, we ascertained that RAB5A depletion in TNBC cells suppresses the secretion of exosomes and blocks the polarization of macrophages toward an M2 phenotype. By scanning miRNAs associated with macrophage polarization, we identified that miR-21 was the pivotal component in tumor cell-derived exosomes and played a key role in RAB5A-mediated macrophage polarization. The enhanced expression of miR-21 in macrophages is able to potentiate the M2 polarization of macrophages in the presence of tumor cells. Pellino-1 (PELI1) was subsequently identified as the target of miR-21, and forced PELI1 expression partially abrogated the M2 polarization of macrophages induced by miR-21 overexpression. Macrophages stimulated with RAB5A-depleted TNBC cells (coculture, conditioned medium or exosomes) impaired their capability to promote the proliferation, migration, and invasion of tumor cells. In vivo xenograft experiments further confirmed that RAB5A knockdown TNBC cells exhibited reduced tumor formation and impaired tumor-associated macrophage recruitment. These studies shed light on the potential underlying mechanism of RAB5A-mediated macrophage polarization in an exosomal miR-21-dependent manner and provide an experimental basis for the development of RAB5A- or exosome-based tumor therapeutic strategies.

Nrf2 prevents diabetic cardiomyopathy via antioxidant effect and normalization of glucose and lipid metabolism in the heart.

Metabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. Here, we investigated in a cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) the direct effect of Nrf2 on cardiomyocytes in DCM and its mechanism. In this study, cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) were used to directly observe whether cardiomyocyte-specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. Compared to wild-type mice, Nrf2-TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin-induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. These results showed that Nrf2 can directly act on cardiomyocytes to exert a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by directly targeting lipid metabolic pathway of AMPK/Sirt1/PGC-1α activation via upstream genes of sestrin2 and LKB1, and indirectly enabling AKT/GSK-3ß/HK-Ⅱ activity via AMPK mediated p70S6K inhibition.

Complexation of bovine lactoferrin with selected phenolic acids via non-covalent interactions: binding mechanism and altered functionality.

Non-covalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals (vdW) and hydrogen bonding (H-bonds) for GA, and hydrophobic forces for others. Conformation of LF was impacted at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, while RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF (P < 0.05), as demonstrated by DPPH, ABTS, FRAP models. CA, CGA, and RA significantly decreased the ESI and improved foam ability of LF (P < 0.05), and the effect of CA and RA was the most remarkable, respectively.

Simulation clinic waste audit assessment and recommendations at the University of Washington School of Dentistry.

OBJECTIVE: Dentistry produces waste contributing to climate change and adverse health outcomes, thus reducing waste is essential; however, there has been minimal emphasis on sustainability or climate action in dentistry. Waste audits quantify the type and amount of waste produced and may inform waste reduction strategies. We conducted a waste audit to identify areas of potential waste reduction and recommend interventions to reduce waste. METHODS: In this cross-sectional study, we conducted a waste audit of garbage produced during a typical 4-hour pre-clinical restorative dentistry simulation exercise. The sample was composed of 72 second-year dental students. This exercise is part of a standard curriculum with a uniform format regarding supplies used and participants. Potentially infectious materials were not used during this exercise. RESULTS: In total, 26.6 kg of waste was discarded. Plastic was the largest contributor by mass (57.5%), followed by paper barriers (19.6%), then impression materials (6.5%). We found 894 gloves and 70 masks discarded. CONCLUSIONS: Based on these findings, we categorized waste reduction opportunities into policy changes, purchasing sustainable materials, and increasing awareness through education. Specific suggested actions include: relaxing glove and gown requirements during laboratory simulations; replacing single use items with more sustainable options; increasing use of intraoral scanners; and posting informational signage with examples of what can be recycled.

Efficient and heritable A-to-K base editing in rice and tomato.

Cytosine and adenosine base editors (CBE and ABE) have been widely used in plants, greatly accelerating gene function research and crop breeding. Current base editors can achieve efficient A-to-G and C-to-T/G/A editing. However, efficient and heritable A-to-Y (A-to-T/C) editing remains to be developed in plants. In this study, a series of A-to-K base editor (AKBE) systems were constructed for monocot and dicot plants. Furthermore, nSpCas9 was replaced with the PAM-less Cas9 variant (nSpRY) to expand the target range of the AKBEs. Analysis of 228 T0 rice plants and 121 T0 tomato plants edited using AKBEs at 18 endogenous loci revealed that, in addition to highly efficient A-to-G substitution (41.0% on average), the plant AKBEs can achieve A-to-T conversion with efficiencies of up to 25.9 and 10.5% in rice and tomato, respectively. Moreover, the rice-optimized AKBE generates A-to-C conversion in rice, with an average efficiency of 1.8%, revealing the significant value of plant-optimized AKBE in creating genetic diversity. Although most of the A-to-T and A-to-C edits were chimeric, desired editing types could be transmitted to the T1 offspring, similar to the edits generated by the traditional ABE8e. Besides, using AKBEs to target tyrosine (Y, TAT) or cysteine (C, TGT) achieved the introduction of an early stop codon (TAG/TAA/TGA) of target genes, demonstrating its potential use in gene disruption.

Hierarchically Assembled Nanofiber Scaffold Guides Long Bone Regeneration by Promoting Osteogenic/Chondrogenic Differentiation of Endogenous Mesenchymal Stem Cells.

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.

Specific rules for time and space of multisensory plasticity in the superior colliculus.

Cat superior colliculus (SC) neurons commonly combine information from different senses, which facilitates event detection and localization. Integration in SC multisensory neurons depends on the spatial and temporal relationships between cross-modal cues. Here, we revealed the parallel process of short-term plasticity in the temporal/spatial integration process during adulthood that adapts multisensory integration to reliable changes in environmental conditions. Short-term experience alters the temporal preferences of SC multisensory neurons, and this short-term plasticity in the temporal/spatial integration process is limited to changes in cross-modal timing (a factor commonly induced by events at different distances from the receiver). However, this plasticity was not evident in response to changes in the cross-modal spatial configuration.

Causal association between tea consumption and head and neck cancer: a Mendelian randomization study.

Although evidence supports an observational association between tea consumption and susceptibility to head and neck cancer, the causal nature of this association remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to determine the causal effects of tea consumption on head and neck cancer. We employed a fixed-effects inverse variance-weighted model for the MR analysis. Genome-wide association study (GWAS) summary data for tea consumption were obtained from the UK Biobank Consortium, and GWAS data for head and neck cancer were derived from two data sources and were used as the outcomes. Our MR analysis revealed limited evidence for a causal relationship between various types of tea intake and head and neck cancer. After adjustment for smoking and alcohol consumption, there was no causal relationship between tea consumption and head and neck cancer. Further experimental studies are required to confirm its potential role in these malignancies.

Deep learning applications in vascular dementia using neuroimaging.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second common cause of dementia after Alzheimer's disease, and deep learning has emerged as a critical tool in dementia research. The aim of this article is to highlight the current deep learning applications in VaD-related imaging biomarkers and diagnosis. RECENT FINDINGS: The main deep learning technology applied in VaD using neuroimaging data is convolutional neural networks (CNN). CNN models have been widely used for lesion detection and segmentation, such as white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), lacunes, cortical superficial siderosis, and brain atrophy. Applications in VaD subtypes classification also showed excellent results. CNN-based deep learning models have potential for further diagnosis and prognosis of VaD. SUMMARY: Deep learning neural networks with neuroimaging data in VaD research represent significant promise for advancing early diagnosis and treatment strategies. Ongoing research and collaboration between clinicians, data scientists, and neuroimaging experts are essential to address challenges and unlock the full potential of deep learning in VaD diagnosis and management.

A genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients.

Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of CXCR4 for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, n = 238; Cohort 2, n = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in CXCR4 and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between CXCR4 SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of CXCR4, rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log10 IU/mL; P = 1.51 × 10-4), a lower mean hepatitis B surface antigen (HBsAg) level (P = 4.76 × 10-4), and a higher mean HBsAg decline (P = 3.88 × 10-4) at Week 72 were achieved. Moreover, a PGS integrating CXCR4_rs28367495 and five previously reported SNPs was strongly correlated with CR (P = 1.26 × 10-13), HBsAg level (P = 4.90 × 10-4), and HBsAg decline (P = 0.005) in all the patients of the two cohorts. CXCR4_rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.

Structure and functionality of whey protein, pea protein, and mixed whey and pea proteins treated by pH shift or high-intensity ultrasound.

Three modifications (pH shift, ultrasound, combined pH shift and ultrasound) induced alterations in pure whey protein isolate (WPI), pea protein isolate (PPI), and mixed whey and pea protein (WPI-PPI) were investigated. The processing effect was related to the protein type and technique used. Solubility of WPI remained unchanged by various treatments. Particle size was enlarged by pH shift while reduced by ultrasound and combined approach. All methods exposed more surface hydrophobic groups on WPI, while pH shift and joint processing was detrimental to its emulsifying activity. The PPI and mixture exhibited similar responses toward the modifications. Solubility of PPI and the blend enhanced in the sequence of pH shift and ultrasound > ultrasound > pH shift. Individual approach expanded while co-handling diminished the particle diameter. Treatments also caused more disclosure of hydrophobic regions in PPI and WPI-PPI and emulsifying activity was ameliorated in the order of pH shift and ultrasound > ultrasound > pH shift.

Contribution of serum elements to blood pressure during pregnancy by impacting gut microbiota: A prospective cohort study.

Exposure to environmental elements can alter gut microbiota, further affecting host health. Exploring the interrelationships among element exposure, gut microbiota and blood pressure (BP) during pregnancy, as well as the mediating roles of gut microbiota, is warranted, which holds implications for maternal and offspring health. In a prospective cohort study between 2017-2018, 733 pregnant women were included. The serum elements and gut microbiota during the second trimester were assessed, and BP was collected during the second and third trimester and before delivery. Fourteen associations were identified between serum elements and BP, including positive associations of zinc (Zn) and thallium (Tl) with systolic BP during the second trimester. Rubidium (Rb) showed a positive association with Pielou's evenness. Serum elements, such as Tl and Rb, were significantly associated with the relative abundance of bacteria and co-abundance groups (CAGs). Alpha diversity was negatively associated with BP levels and trajectories. Moreover, 15 associations between gut microbiota and BP were shown. Finally, mediation analysis confirmed that CAG2 and Pielou's evenness mediated the associations of Tl and Rb with BP, respectively. We concluded that serum elements can contribute to BP changes during pregnancy through gut microbiota, suggesting gut microbiota-targeted approach as a potential intervention.

The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin ßA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-ß/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. METHODS: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. RESULTS: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3'UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. CONCLUSIONS: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.