Fabrication of Zn-Air Battery with High Output Capacity Under Ultra-Large Current.

Zn-air battery (ZAB) is advocated as a more viable option in the new-energy technology. However, the limited-output capacity at a high current density impedes the driving range in power batteries substantially. Here, a novel heterojunction-based graphdiyne (GDY) and Ag29Cu7 alloy quantum dots (Ag29Cu7 QDs/GDY) for constructing a high-performance aqueous ZAB are fabricated. The as-fabricated ZAB achieves discharge at up to 100 mA cm-2 (the highest value ever reported) along with a remarkable output specific capacity of 786.2 mAh g-1 Zn, which is mainly benefitted from the binary-synergistic effect toward a stable triple-phase interface for air electrode induced by the Ag29Cu7 QDs and GDY in harsh base, together with the decreasing reaction energy barrier and polarization. The results outperform the superior reports discharging at low current and will bring breakthrough progress toward the practical applications of ZAB on large power supply facilities.

Prelacrimal recess approach for maxillary sinus inverted papilloma: a 15-year experience from a single center.

PURPOSE: This large retrospective, single-center, follow-up study investigated the endoscopic prelacrimal recess approach (PLRA) for treating maxillary sinus inverted papilloma (MSIP). METHODS: Between January 2007 and November 2022, patients with MSIP treated with PLRA were enrolled. Data on clinical manifestations, imaging, and surgical procedures were collected. The visual analog scale (VAS) scores for maxillofacial numbness and nasal symptoms and the SNOT-22 nasal symptom scores were statistically analyzed. RESULT: Of 122 patients (68 males and 54 females) enrolled in the study, with a mean age of 50.75 ± 12.84 years (26-80 years), 111 patients underwent PLRA, nine underwent modified PLRA, one converted to an endoscopic medial maxillectomy (EMM), and one to an endoscopic modified Denker's approach. The average follow-up was 86.60 (13-192) months, the recurrence rate was 3.28%, and 29 patients (23.77%) complained of maxillofacial numbness one month postoperatively, which disappeared in most cases one year after surgery. Five patients (4.10%) experienced mild numbness at the end of the follow-up period. Maxillary sinus ostium contracture or atresia occurred in two cases (1.64%). After surgery, the VAS nasal symptom scores improved significantly (P < 0.001). SNOT-22 indicated that the most common postoperative symptom was thick nasal discharge. CONCLUSION: PLRA is a flexible first-choice surgical treatment for maxillary sinus inverted papilloma and can be modified according to the extent of the lesion, the surgeon's experience and technique, and surgical instruments. That can help achieve complete resection and reduce recurrence and surgical complications. Upper teeth numbness, the most common postoperative complication, tends to disappear after 1 year.

Whole exome sequencing and transcriptome analysis in two unrelated patients with novel SET mutations.

The human SET nuclear proto-oncogene (SET) gene is a protein-coding gene that encodes proteins that affects chromatin remodeling and gene transcription. Mutations in the SET gene have been reported to cause intellectual disability (ID) and epilepsy. In this study, we collected and analyzed clinical, genetic, and transcript features of two unrelated Chinese patients with ID. Both patients were characterized by moderate intellectual disability. Whole-exome sequencing identified two novel heterozygous mutations in the SET gene: NM_001122821.1:c.532-3 T > A and NM_001122821.1:c.3 G > C (p.0?). Additionally, RNA sequencing revealed widespread dysregulation of genes involved in NF-kB signaling and neuronal system in these two patients. To our knowledge, this is the first report of SET mutations causing ID in the Chinese population, broadening the genetic and ethnic spectrum of SET-related disorders and highlighting the importance of screening for SET gene variants.

Critical miRNAs in regulating pulmonary hypertension: A focus on Signaling pathways and therapeutic Targets.

Pulmonary hypertension (PH) is complex disease as a result of obstructive pulmonary arterial remodeling, which in turn results in elevated pulmonary arterial pressure (PAP) and subsequent right ventricular heart failure, eventually leading to premature death. However, there is still a lack of a diagnostic blood-based biomarker and therapeutic target for PH. Because of the difficulty of diagnosis, new and more easily accessible prevention and treatment strategy are being explored. New target and diagnosis biomarkers should also allow for early diagnosis. In biology, miRNAs are short endogenous RNA molecules that are not coding. It is known that miRNAs can regulate gene expression and affect a variety of biological processes. Besides, miRNAs have been proven to be a crucial factor in PH pathogenesis. miRNAs have various effects on pulmonary vascular remodeling and are expressed differentially in various pulmonary vascular cells. Nowadays, it has been shown to be critical in the functions of different miRNAs in the pathogenesis of PH. Therefore, clarifying the mechanism of miRNAs regulating pulmonary vascular remodeling is of great importance to explore new therapeutic targets of PH and improve the survival qualify and time of patients. This review is focused on the role, mechanism, and potential therapeutic targets of miRNAs in PH and puts forward possible clinical treatment strategies.

Tumor Targeting and pH-Sensitive Inclusion Complex Based on HP-ß-CD as a Potential Carrier for Paclitaxel: Fabrication, Molecular Docking, and Characterization.

In this study, a tumor-targeting and pH-sensitive inclusion complex based on the host-guest recognition between the chitosan and folic acid grafted HP-ß-CD (FA-CS-CD) and stearic acid modified 2-benzimidazolemethanol (BM-SA) was designed and fabricated for the controlled delivery of paclitaxel (PTX). Through the combination of computational simulations and experiments, the interaction between FA-CS-CD, BM-SA, and PTX was investigated, and the optimized preparation method was obtained. For the optimized PTX-loaded FA-CS-CD/BM-SA inclusion complex, the particle size and zeta potential were 146 nm and +15.4 mV, respectively. In vitro drug release study revealed the pH-triggered drug release behavior of the inclusion complex. Both in vitro and in vivo evaluations demonstrated that the PTX-loaded FA-CS-CD/BM-SA inclusion complex exhibited enhanced antitumor efficiency and minimized systemic toxicity. This system might be a promising carrier for PTX.

The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents.

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.

The classification of flash visual evoked potential based on deep learning.

BACKGROUND: Visual electrophysiology is an objective visual function examination widely used in clinical work and medical identification that can objectively evaluate visual function and locate lesions according to waveform changes. However, in visual electrophysiological examinations, the flash visual evoked potential (FVEP) varies greatly among individuals, resulting in different waveforms in different normal subjects. Moreover, most of the FVEP wave labelling is performed automatically by a machine, and manually corrected by professional clinical technicians. These labels may have biases due to the individual variations in subjects, incomplete clinical examination data, different professional skills, personal habits and other factors. Through the retrospective study of big data, an artificial intelligence algorithm is used to maintain high generalization abilities in complex situations and improve the accuracy of prescreening. METHODS: A novel multi-input neural network based on convolution and confidence branching (MCAC-Net) for retinitis pigmentosa RP recognition and out-of-distribution detection is proposed. The MCAC-Net with global and local feature extraction is designed for the FVEP signal that has different local and global information, and a confidence branch is added for out-of-distribution sample detection. For the proposed manual features,a new input layer is added. RESULTS: The model is verified by a clinically collected FVEP dataset, and an accuracy of 90.7% is achieved in the classification task and 93.3% in the out-of-distribution detection task. CONCLUSION: We built a deep learning-based FVEP classification algorithm that promises to be an excellent tool for screening RP diseases by using FVEP signals.

Divergence of Tbx4 hindlimb enhancer HLEA underlies the hindlimb loss during cetacean evolution.

The cetacean hindlimb skeleton massively decreased to only vestigial limb elements as cetaceans evolved from land to aquatic lifestyles; however, the molecular mechanism underlying this major morphological transition remains unclear. In this study, four deletions and specific substitutions were detected in cetacean hindlimb enhancer A (HLEA), an enhancer that can regulate Tbx4 expression in hindlimb tissues to control hindlimb development. Transcriptional activation of HLEA was significantly weaker in bottlenose dolphin than mice, and this was found to be closely associated with cetacean-specific deletions. Furthermore, deletions in cetacean HLEA might disrupt HOX and PITX1 binding sites, which are required for enhancer activation. The ancestral state of these deletions was investigated, and all four specific deletions were found to have occurred after the species diverged from their common ancestor, suggesting that the deletion occurred recently, during a secondary aquatic adaptation. Taking these findings together, we suggest that cetacean-specific sequence changes reduced the Tbx4 gene expression pattern, and consequently drove the gradual loss of hindlimb in cetaceans.

Stem Cell Membrane-Encapsulated Zeolitic Imidazolate Framework-8: A Targeted Nano-Platform for Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) have been recognized as one of the most promising pharmaceutical multipotent cells, and a key step for their wide application is to safely and efficiently regulate their activities. Various methods have been proposed to regulate the directional differentiation of MSCs during tissue regeneration, such as nanoparticles and metal ions. Herein, nanoscale zeolitic imidazolate framework-8 (ZIF-8), a Zn-based metal-organic framework, is modified to direct MSCs toward an osteoblast lineage. Specifically, ZIF-8 nanoparticles are encapsulated using stem cell membranes (SCMs) to mimic natural molecules and improve the biocompatibility and targeted ability toward MSCs. SCM/ZIF-8 nanoparticles adjust the sustained release of Zn2+ , and promote their specific internalization toward MSCs. The internalized SCM/ZIF-8 nanoparticles show excellent biocompatibility, and increase MSCs' osteogenic potentials. Moreover, RNA-sequencing results elucidate that the activated cyclic adenosine 3,5-monophosphate (cAMP)-PKA-CREB signaling pathway can be dominant in accelerating osteogenic differentiation. In vivo, SCM/ZIF-8 nanoparticles greatly promote the formation of new bone tissue in the femoral bone defect detected by 3D micro-CT, hematoxylin and eosin staining, and Masson staining after 4 weeks. Overall, the SCM-derived ZIF-8 nanostructures achieve the superior targeting ability, biocompatibility, and enhanced osteogenesis, providing a constructive design for tissue repair.

Efficacy prediction of noninvasive ventilation failure based on the stacking ensemble algorithm and autoencoder.

BACKGROUND: Early prediction of noninvasive ventilation failure is of great significance for critically ill ICU patients to escalate or change treatment. Because clinically collected data are highly time-series correlated and have imbalanced classes, it is difficult to accurately predict the efficacy of noninvasive ventilation for severe patients. This paper aims to precisely predict the failure probability of noninvasive ventilation before or in the early stage (1-2 h) of using it on patients and to explain the correlation of the predicted results. METHODS: In this paper, we proposed a SMSN model (stacking and modified SMOTE algorithm of prediction of noninvasive ventilation failure). In the feature generation stage, we used an autoencoder algorithm based on long short-term memory (LSTM) to automatically extract time series features. In the modelling stage, we adopted a modified SMOTE algorithm to address imbalanced classes, and three classifiers (logistic regression, random forests, and Catboost) were combined with the stacking ensemble algorithm to achieve high prediction accuracy. RESULTS: Data from 2495 patients were used to train the SMSN model. Among them, 80% of 2495 patients (1996 patients) were randomly selected as the training set, and 20% of these patients (499 patients) were chosen as the testing set. The F1 of the proposed SMSN model was 79.4%, and the accuracy was 88.2%. Compared with the traditional logistic regression algorithm, the F1 and accuracy were improved by 4.7% and 1.3%, respectively. CONCLUSIONS: Through SHAP analysis, oxygenation index, pH and H1FIO2 collected after 1 h of noninvasive ventilation were the most relevant features affecting the prediction.

AIE-Featured Redox-Sensitive Micelles for Bioimaging and Efficient Anticancer Drug Delivery.

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.

[Comparative Evaluation of the Value of Quantitative Parameters of Dual-energy CT and MRI for KRAS Mutation in Rectal Cancer].

Objective To evaluate and compare the value of quantitative parameters of preoperative dual-energy CT and MRI on KRAS mutation in rectal cancer,and to explore the correlations between postoperative pathological indicators and KRAS mutation. Methods This study retrospectively analyzed 50 patients with rectal cancer confirmed by surgery and pathology and receiving KRAS genetic testing in Lanzhou University Second Hospital from August 2017 to April 2021.According to the results of genetic testing,the patients were assigned into a wild-type group (29 patients) and a mutant type group (21 patients).The preoperative baseline data included sex,age,and serum tumor markers,and the postoperative pathological data included pathological stage,lymphovascular invasion,perineural invasion,and lymph node metastasis.The quantitative parameters of three-phase energy spectral CT included iodine (water) concentration,water (iodine) concentration,effective atomic number,and normalized iodine concentration.The quantitative parameters of apparent diffusion coefficient (ADC) included minimum ADC,average ADC,and relative ADC.In addition,the width of the superior rectal vein was obtained from the CT images of the venous phase,and the tumor segmentation,the maximum axial length of tumor,and the maximum longitudinal length of tumor were obtained from the MRI images.The qualitative and quantitative data were compared by χ2 test,t-test,and Mann-Whitney U test.The diagnostic efficacy of the two detection methods for KRAS mutations in rectal cancer was compared,and the receiver operating characteristic curve was employed to evaluate the diagnostic efficacy. Results The KRAS mutation rate was higher in the carbohydrate antigen 199 abnormal group than the normal group (P=0.036) and higher in the positive group of lymphovascular invasion (P=0.034).The KRAS mutant type group had higher normalized iodine concentration in the venous phase (P=0.016) and lower average ADC and relative ADC (P=0.008, P=0.002,respectively) than the wild-type group.Among them,relative ADC had the highest diagnostic efficiency (AUC=0.755). Conclusion The quantitative parameters of dual-energy CT and ADC have similar diagnostic efficiency for KRAS mutation in rectal cancer,and relative ADC is superior to other parameters.

Humins with Efficient Electromagnetic Wave Absorption: A By-Product of Furfural Conversion to Isopropyl Levulinate via a Tandem Catalytic Reaction in One-Pot.

Both one-pot catalytic conversion of furfural (FAL) to isopropyl levulinate (PL) and carbonization of by-product (humins) for electromagnetic wave absorption are discussed, which provides inspiration that humins can be applied to electromagnetic wave absorption. In the former, phosphotungstic acid (PW) is employed as a homogeneous catalyst to convert FAL to PL via a tandem reaction in one pot, with the formation of a vast amount of humins. With FAL and various intermediates as substrates, it was found that humins was a polymerization product of FAL, furfuryl alcohol (FOL) and furfuryl ester (FE) with furan rings. In addition, the in situ attenuated total reflection infrared (ATR-IR) spectra also provided a basis for the proposed reaction route. In the latter, with the humins as raw material, P species and WO3 doped nano-porous carbon (Humins-700) platform formed after high-temperature annealing is used for electromagnetic wave absorption and manifests desirable absorption performance. The minimum reflection loss (RLmin ) value is -47.3 dB at 13.0 GHz with a thickness of 2.0 mm and the effective absorption bandwidth reaches 4.5 GHz (11.2-5.7 GHz).

A pH-Sensitive Polymeric Micellar System Based on Chitosan Derivative for Efficient Delivery of Paclitaxel.

In this study, an amphiphilic conjugate based on mPEG and cholesterol-modified chitosan with hydrazone bonds in the molecules (mPEG-CS-Hz-CH) was successfully synthesized. Using the polymer as the carrier, the paclitaxel (PTX)-loaded mPEG-CS-Hz-CH micelles were prepared by an ultrasonic probe method. The mean particle size and zeta potential of the optimized PTX-loaded micelles were 146 ± 4 nm and +21.7 ± 0.7 mV, respectively. An in vitro drug release study indicated that the PTX-loaded mPEG-CS-Hz-CH micelles were stable under normal physiological conditions (pH 7.4), whereas rapid drug release was observed in the simulated tumor intracellular microenvironment (pH 5.0). An in vitro cytotoxicity study demonstrated the non-toxicity of the polymer itself, and the PTX-loaded micelles exhibited superior cytotoxicity and significant selectivity on tumor cells. An in vivo antitumor efficacy study further confirmed that the PTX-loaded micelles could improve the therapeutic efficacy of PTX and reduce the side effects. All these results suggested that the mPEG-CS-Hz-CH micelles might be promising pH-sensitive nanocarriers for PTX delivery.

Molecular characterization of a novel botoulivirus from the phytopathogenic fungus Sclerotinia minor.

In this study, the complete genomic sequence of a novel botoulivirus (Sclerotinia minor botoulivirus 1, SmBV1) from the phytopathogenic fungus Sclerotinia minor strain LC45 was determined. The genome of SmBV1 is 2,882 nucleotides in length and contains a single large open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis showed that SmBV1 clustered with the botoulivirus clade within the family Botourmiaviridae. This is the first report of a botoulivirus in S. minor.

Ligand-free upconversion nanoparticles for cell labeling and their effects on stem cell differentiation.

Recently, the wide application of upconversion nanoparticles (UCNPs) in the field of bioimaging has raised the requirement of biocompatibility. Current cytocompatibility studies on UCNPs mainly focus on cancer cells; however, their potential effects on normal cells are rarely addressed. Herein, the cellular effects of a trace amount of ligand-free NaYF4:Yb/Er nanocrystals on the differentiation of rat bone mesenchymal stem cells (rBMSCs) were investigated. First, due to their excellent upconversion fluorescent properties, the cellular uptake of ligand-free NaYF4:Yb/Er nanocrystals was confirmed by confocal laser scanning microscopy, and a homogeneous cytoplasmic distribution was imaged. Second, the viability of the rBMSCs cultured with a series of concentrations of nanoparticles (0, 30, 300, and 3000 ng ml-1) was evaluated, and a dose threshold was determined. Third, the effects of ligand-free NaYF4:Yb/Er nanocrystals on the osteogenesis of the rBMSCs were intensively characterized. The alkaline phosphatase activity assay, quantitative real time polymerase chain reaction for related osteogenic genes, and immunofluorescence staining of specific biomarkers and mineral deposits demonstrated that the ligand-free NaYF4:Yb/Er nanocrystals at a proper concentration can enhance osteogenic differentiation. Finally, intracytoplasmic lipid detection showed that the adipogenic differentiation of rBMSCs might be inhibited in the presence of ligand-free NaYF4:Yb/Er nanocrystals. Meanwhile, these results showed that the effects of ligand-free NaYF4:Yb/Er nanocrystals on rBMSCs were concentration-dependent and reciprocal between osteogenic and adipogenic differentiation. This work provides new insights into the exploring the biocompatibility of UCNPs and will benefit the research community engaged in nanotechnology and biomedicine.

miR-378 and its host gene Ppargc1ß exhibit independent expression in mouse skeletal muscle.

MicroRNAs (miRNAs) are implicated in multiple biological processes in physiological and pathological settings. Nearly half of the known miRNAs are classified as 'intronic' miRNAs because they are embedded within the introns of protein-coding or noncoding genes. Such miRNAs were thought to be processed from primary host gene transcripts and share the promoter of their host. Recent analyses predicted that some intronic miRNAs might be transcribed and regulated as independent units, but there is little direct evidence for this in a specific biological context. Here, we focused on miR-378, which is located within the first intron of the peroxisome proliferator-activated receptor γ coactivator 1-beta (Ppargc1ß) gene and critically regulates skeletal muscle cell differentiation and muscle regeneration. We demonstrate that miR-378 and Ppargc1ß exhibit distinct expression patterns during skeletal muscle cell differentiation. In terminally differentiated adult skeletal muscle tissues of mice, miR-378 is predominantly expressed in glycolytic muscle, whereas Ppargc1ß is mainly expressed in oxidative soleus muscle. Mechanistically, miR-378, but not Ppargc1ß, is regulated by the transcription factor, MyoD, in muscle cells. Our findings identify a regulatory model of miR-378 expression, thereby helping us to understand its physiological function in skeletal muscle.

The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats.

PURPOSE: To investigate the effect of spleen tyrosine kinase (Syk) inhibitor R406 on diabetic retinopathy (DR) in diabetic mellitus (DM) rats. METHODS: Rats were randomized into Normal, DM, DM + 5 mg/kg R406 and DM + 10 mg/kg R406 groups. DM rats were established via injection of streptozotocin (STZ). One week after model establishment, rats in treatment groups received 5 mg/kg or 10 mg/kg R406 by gavage administration for 12 weeks consecutively, followed by the detection with hematoxylin-eosin (HE) staining, Evans blue angiography, retinal trypsin digestion assay, Western blotting, immunohistochemistry, TUNEL assay, immunofluorescence assay and quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR). RESULTS: The retina of DM rats presented different degree of edema, disordered and loose structure, swollen cells with enlarged intercellular space, and dilated and congested capillaries. Besides, the retinal vessels of DM rats showed high fluorescence leakage. However, R406 alleviated the above-mentioned conditions, which was much better with high concentration of R406 (10 mg/kg). R406 also reversed the down-regulations of occludin, claudin-5, ZO-1 and the up-regulation of and VEGF in retinal tissues of DM rats; inhibited retinal cell apoptosis; strengthened retinal cell proliferation; and reduced expressions of IL-1ß, IL-6, TNF-α and nuclear p65 NF-κB in retinal tissues. The improvement in all these indexes was much more significant in rats of DM + 10 mg/kg R406 group than in rats of DM + 5 mg/kg R406 group. CONCLUSION: Syk inhibitor R406 could attenuate retinal inflammation in DR rats via the repression of NF-κB activation.

LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/ BCAT1 axis.

OBJECTIVE: To investigate the impact of long noncodingRNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) on hepatocellular cancer (HCC) cell propagation, invasion, and migration by mediating miR-203/ BCAT1 axis. METHODS: Microarray analysis was based on 25 pairs of HCC cancerous tissues and adjacent tissues. The expression levels of CRNDE, miR-203, and BCAT1 in HCC tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The liver cell line L-02 and HCC cell lines HepG2 and Huh-7 were utilized to assess the regulatory effects of CRNDE and miR-203 on HCC progression in vitro. Western blot was used to qualify BCAT1 protein expression level. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analysis, whereas cell invasion and migration assay were performed by the Transwell assay. The relationship among CRNDE, miR-203, and BCAT1 was validated by dual luciferase assay. Tumor Xenograft study was established to verify the pathological effect of CRNDE on HCC development in vivo. RESULTS: The expression levels of the CRNDE and BCAT1 were upregulated in HCC tissues and cells, whereas miR-203 was downregulated in HCC. Knockdown of CRNDE or miR-203 overexpression would inhibit HCC cell propagation and metastasis, and induced cell apoptosis. Moreover, miR-203 was negatively correlated with CRNDE, the same as miR-203 with BCAT1. Dual luciferase assay showed that miR-203 was an inhibitory target of CRNDE, and BCAT1 was directly targeted by miR-203 as well. CONCLUSION: LncRNA CRNDE could enhance HCC tumorgenesis by sponging miR-203 and mediating BCAT1. LncRNA CRNDE might facilitate HCC cell propagation, invasiveness, and migration through regulating miR-203/ BCAT1 axis.

PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer.

BACKGROUND: CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. METHODS: Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. RESULTS: CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. CONCLUSIONS: PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.