A solution-processed n-type conducting polymer with ultrahigh conductivity.

Conducting polymers (CPs) with high conductivity and solution processability have made great advances since the pioneering work on doped polyacetylene1-3, thus creating the new field of 'organic synthetic metals,4. Various high-performance CPs have been realized, which enable the applications of several organic electronic devices5,6. Nevertheless, most CPs exhibit hole-dominant (p-type) transport behaviour7,8, whereas the development of n-type analogues lags far behind and only a few exhibit metallic state, typically limited by low doping efficiency and ambient instability. Here we present a facilely synthesized highly conductive n-type polymer poly(benzodifurandione) (PBFDO). The reaction combines oxidative polymerization and in situ reductive n-doping, greatly increasing the doping efficiency, and a doping level of almost 0.9 charges per repeating unit can be achieved. The resultant polymer exhibits a breakthrough conductivity of more than 2,000 S cm-1 with excellent stability and an unexpected solution processability without extra side chains or surfactants. Furthermore, detailed investigations on PBFDO show coherent charge-transport properties and existence of metallic state. The benchmark performances in electrochemical transistors and thermoelectric generators are further demonstrated, thus paving the way for application of the n-type CPs in organic electronics.

Copper Difluorocarbene Enables Catalytic Difluoromethylation.

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

Lycorine relieves the CCl4-induced liver fibrosis mainly via the JAK2/STAT3 and PI3K/AKT signaling pathways.

Liver fibrosis, a progressive process of fibrous scarring, results from the accumulation of extracellular matrix proteins (ECM). If left untreated, it often progresses to diseases such as cirrhosis and hepatocellular carcinoma. Lycorine, a natural alkaloid derived from medicinal plants, has shown diverse bioactivities by targeting JAK2/STAT3 signaling, but its pharmacological effects and potential molecular mechanisms in liver fibrosis remains largely unexplored. The purpose of this study is to elucidate the pharmacological activity and molecular mechanism of lycorine in anti-hepatic fibrosis. Findings indicate that lycorine significantly inhibited hepatic stellate cells (HSCs) activation by reducing the expression of α-SMA and collagen-1. In vivo, lycorine treatment alleviated carbon tetrachloride (CCl4) -induced mice liver fibrosis, improving liver function, decreasing ECM deposition, and inhibiting fibrosis-related markers' expression. Mechanistically, it was found that lycorine exerts protective activity through the JAK2/STAT3 and PI3K/AKT signaling pathways, as evidenced by transcriptome sequencing technology and small molecule inhibitors. These results underscore lycorine's potential as a therapeutic drug for liver fibrosis.

Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.

Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes.

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.

Research advances in microfluidic collection and detection of virus, bacterial, and fungal bioaerosols.

Bioaerosols are airborne suspensions of fine solid or liquid particles containing biological substances such as viruses, bacteria, cellular debris, fungal spores, mycelium, and byproducts of microbial metabolism. The global Coronavirus disease 2019 (COVID-19) pandemic and the previous emergence of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza have increased the need for reliable and effective monitoring tools for bioaerosols. Bioaerosol collection and detection have aroused considerable attention. Current bioaerosol sampling and detection techniques suffer from long response time, low sensitivity, and high costs, and these drawbacks have forced the development of novel monitoring strategies. Microfluidic technique is considered a breakthrough for high performance analysis of bioaerosols. In recent years, several emerging methods based on microfluidics have been developed and reported for collection and detection of bioaerosols. The unique advantages of microfluidic technique have enabled the integration of bioaerosol collection and detection, which has a higher efficiency over conventional methods. This review focused on the research progress of bioaerosol collection and detection methods based on microfluidic techniques, with special attention on virus aerosols and bacterial aerosols. Different from the existing reviews, this work took a unique perspective of the targets to be collected and detected in bioaerosols, which would provide a direct index of bioaerosol categories readers may be interested in. We also discussed integrated microfluidic monitoring system for bioaerosols. Additionally, the application of bioaerosol detection in biomedicine was presented. Finally, the current challenges in the field of bioaerosol monitoring are presented and an outlook given of future developments.

Molecular cloning and functional characterization of peroxinectin from red swamp crayfish, Procambarus clarkii.

Peroxinectin, which has both peroxidase and cell adhesion activities, is crucial for invertebrate innate immune responses. In this study, we first cloned the full-length cDNA of Procambarus clarkii Peroxinectin (denoted as Pc-Px) and evaluated its immune roles. The Pc-Px cDNA had 2460 base pairs (bp) and 819 amino acid residues, including peroxidase domain and a putative integrin-binding motif. Pc-Px tissue expression was found to be ubiquitous in all examined tissues under normal physiological conditions. Pc-Px mRNA levels were highest in hemocytes, followed by gills and heart, and were lowest in the gut. The LPS, PGN, and Poly I:C treatment significantly up-regulated the transcript level of Pc-Px gene, but the expression trends were different after the microbials component treatments. Pc-Px knockdown using double-stranded RNA altered the transcription profiles of various immune-related genes in hepatopancreas of P. clarkii. Taken together, Pc-Px is an important component of immune system that likely to modulate immune function of P. clarkii via regulating immune-associated genes.

Adaptive DBSCAN Clustering and GASA Optimization for Underdetermined Mixing Matrix Estimation in Fault Diagnosis of Reciprocating Compressors.

Underdetermined blind source separation (UBSS) has garnered significant attention in recent years due to its ability to separate source signals without prior knowledge, even when sensors are limited. To accurately estimate the mixed matrix, various clustering algorithms are typically employed to enhance the sparsity of the mixed matrix. Traditional clustering methods require prior knowledge of the number of direct signal sources, while modern artificial intelligence optimization algorithms are sensitive to outliers, which can affect accuracy. To address these challenges, we propose a novel approach called the Genetic Simulated Annealing Optimization (GASA) method with Adaptive Density-Based Spatial Clustering of Applications with Noise (DBSCAN) clustering as initialization, named the CYYM method. This approach incorporates two key components: an Adaptive DBSCAN to discard noise points and identify the number of source signals and GASA optimization for automatic cluster center determination. GASA combines the global spatial search capabilities of a genetic algorithm (GA) with the local search abilities of a simulated annealing algorithm (SA). Signal simulations and experimental analysis of compressor fault signals demonstrate that the CYYM method can accurately calculate the mixing matrix, facilitating successful source signal recovery. Subsequently, we analyze the recovered signals using the Refined Composite Multiscale Fuzzy Entropy (RCMFE), which, in turn, enables effective compressor connecting rod fault diagnosis. This research provides a promising approach for underdetermined source separation and offers practical applications in fault diagnosis and other fields.

Sodium nitroprusside alleviates nanoplastics-induced developmental toxicity by suppressing apoptosis, ferroptosis and inflammation.

The health damage caused by nanoplastics (NPs) pollution has become one of the global scientific problems to be solved urgently. However, the toxicological mechanism of NPs is complex, and the research progress of anti-toxicity is limited. Thus, it has potential application value to explore or develop drugs that can effectively alleviate or remove NPs with biological toxicity. In this research, 8 µM sodium nitroprusside (SNP) solution was used to treat zebrafish larvae with 20 mg/L NPs for up to 12 days, and the results showed that SNP treatments were effective in alleviating NPs-caused developmental toxicity in zebrafish larvae. Further examination of its signaling pathway revealed that NPs-induced oxidative stress was mitigated by activating the NO-sGC-cGMP signaling pathway and reduced most of the reactive oxygen species (ROS). Subsequently, we detected the key substances and the key enzymes involved in apoptosis and ferroptosis, and found that oxidative stress-induced mitochondria-dependent apoptosis and lipid peroxidation-caused ferroptosis were alleviated. Finally, observed the accumulation of NPs and ROS in the liver of zebrafish larvae, which is the target organ of immunotoxicity, and we found that SNP could alleviate NPs-caused inflammation by analyzing the fluorescence intensity of neutrophils and macrophages in transgenic zebrafish and detecting the expression of key immune genes. In conclusion, this research has shown for the first time that SNP treatment can significantly inhibit NPs-induced developmental toxicity, resulting from oxidative stress-induced apoptosis, ferroptosis and inflammation in zebrafish larvae.

AT7519 against lung cancer via the IL6/STAT3 signaling pathway.

Lung cancer is a part of the commonest malignancies with the highest mortality rate in cancer-related deaths worldwide. Signal transducer and activator of transcription 3 (STAT3) and cyclin-dependent kinases (CDKs) are promising prognostic marker and therapeutic target in cancers. Our previous study has demonstrated the closely relationship between CDK9 and STAT3 in lung cancer. The inhibition of cell viability and migration in vitro by AT7519 were evaluated using methyl thiazolyl tetrazolium (MTT) assay, clonogenic assay and scratch wound model. The cell cycle analysis was evaluated using flow cytometry analysis and western blotting analysis. The apoptotic-induced efficiency was assessed by flow cytometry analysis, hoechst 33342 staining, caspase-3 activity analysis and western blotting analysis. The roles of STAT3 in AT7519 treatment for lung cancer were assessed by docking model and western blotting analysis. The patient-derived xenograft (PDX) models were used to investigate the effect of AT7519 in vivo. In this study, we found that AT7519, a CDK inhibitor, reduced the viability of lung cancer cells in vitro and strongly suppressed tumor growth in PDX model. AT7519 blocked cell cycle progression and induced apoptosis by inhibiting IL-6/STAT3 pathway. Taken together, AT519 exhibits great anti-tumor effects in lung cancer, and the mechanism was related closely to IL-6/STAT3 signaling pathway, which suggests the important roles of STAT3 in CDKs inhibitors. AT7519 might be a novel potential therapeutic agent based on this rationale.

Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common lung cancer with high mortality across the world, but it is challenging to develop an effective therapy for NSCLC. Celastrol is a natural bioactive compound, which has been found to possess potential antitumor activity. However, the underlying molecular mechanisms of celastrol activity in NSCLC remain elusive. METHODS: Cellular function assays were performed to study the suppressive role of celastrol in human NSCLC cells (H460, PC-9, and H520) and human bronchial epithelial cells BEAS-2B. Cell apoptosis levels were analyzed by flow cytometry, Hoechst 33342, caspase-3 activity analysis, and western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and fluorescence microscope. Expression levels of endoplasmic reticulum (ER) stress-related proteins and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) were identified via western blot analysis. A heterograft model in nude mice was employed to evaluate the effect of celastrol in vivo. RESULTS: Celastrol suppressed the growth, proliferation, and metastasis of NSCLC cells. Celastrol significantly increased the level of intracellular ROS; thus, triggering the activation of the ER stress pathway and inhibition of the P-STAT3 pathway, and eventually leading to cell apoptosis, and the effects were reversed by the pre-treatment with N-Acetyl-L-cysteine (NAC). Celastrol also suppressed tumor growth in vivo. CONCLUSION: The outcomes revealed that celastrol plays a potent suppressive role in NSCLC in vitro and in vivo. Celastrol induces apoptosis via causing mitochondrial ROS accumulation to suppress the STAT3 pathway. Celastrol may have potential application prospects in the therapy of NSCLC.

GPR37 promotes cancer growth by binding to CDK6 and represents a new theranostic target in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is associated with poor prognosis. Identifying novel cancer targets and helpful therapeutic strategies remains a serious clinical challenge. This study detected differentially expressed genes in The Cancer Genome Atlas (TCGA) LUAD data collection. We also identified a predictive DNA biomarker, G protein-coupled receptor 37 (GPR37), which was verified as a prognostic biomarker with a critical role in tumor progression. In human LUAD specimens and microarray analyses, we determined that GPR37 was significantly upregulated and associated with a poor prognosis. GPR37 downregulation markedly inhibited the proliferation and migration of LUAD both in vitro and in vivo. Mechanistically, GPR37 could bind to CDK6, thereby facilitating tumor progression in LUAD by inducing cell cycle arrest at the G1 phase. GPR37 also facilitates tumorigenesis in xenograft tumors in vivo. High-throughput screening for GPR37-targeted drugs was performed using the Natural Products Library, which revealed the potential of Hypocrellin B to inhibit GPR37 and cell growth in LUAD. We demonstrated that Hypocrellin B suppressed LUAD cell proliferation and migration both in vitro and in vivo via GPR37 inhibition. Collectively, our findings reveal the role of GPR37 in LUAD progression and migration and the potential of GPR37 as a target for the treatment of LUAD. Thus, the specific inhibition of GPR37 by the natural product Hypocrellin B may possess the potential for the treatment of LUAD.

Radiosynthesis and evaluation of a fluorine-18 radiotracer [18F]FS1P1 for imaging sphingosine-1-phosphate receptor 1.

Assessment of sphingosine-1-phosphate receptor 1 (S1PR1) expression could be a unique tool to determine the neuroinflammatory status for central nervous system (CNS) disorders. Our preclinical results indicate that PET imaging with [11C]CS1P1 radiotracer can quantitatively measure S1PR1 expression changes in different animal models of inflammatory diseases. Here we developed a multiple step F-18 labeling strategy to synthesize the radiotracer [18F]FS1P1, sharing the same structure with [11C]CS1P1. We explored a wide range of reaction conditions for the nucleophilic radiofluorination starting with the key ortho-nitrobenzaldehyde precursor 10. The tertiary amine additive TMEDA proved crucial to achieve high radiochemical yield of ortho-[18F]fluorobenzaldehyde [18F]12 starting with a small amount of precursor. Based on [18F]12, a further four-step modification was applied in one-pot to generate the target radiotracer [18F]FS1P1 with 30-50% radiochemical yield, >95% chemical and radiochemical purity, and a high molar activity (37-166.5 GBq µmol-1, decay corrected to end of synthesis, EOS). Subsequently, tissue distribution of [18F]FS1P1 in rats showed a high brain uptake (ID% g-1) of 0.48 ± 0.06 at 5 min, and bone uptake of 0.27 ± 0.03, 0.11 ± 0.02 at 5, and 120 min respectively, suggesting no in vivo defluorination. MicroPET studies showed [18F]FS1P1 has high macaque brain uptake with a standard uptake value (SUV) of ∼2.3 at 120 min. Radiometabolite analysis of macaque plasma samples indicated that [18F]FS1P1 has good metabolic stability, and no major radiometabolite confounded PET measurements of S1PR1 in nonhuman primate brain. Overall, [18F]FS1P1 is a promising F-18 S1PR1 radiotracer worthy of further clinical investigation for human use.

Telocinobufagin Has Antitumor Effects in Non-Small-Cell Lung Cancer by Inhibiting STAT3 Signaling.

Non-small-cell lung carcer (NSCLC), the main histological subtype of lung cancer, is responsible for significant morbidity and mortality worldwide. Telocinobufagin, an active compound of the Chinese traditional medicine ChanSu, has antitumor effects, but its mechanism of action remains unknown. Therefore, we investigated the effect of telocinobufagin on NSCLC growth and metastasis and its possible mechanism of action, in vitro and in vivo. Cell proliferation, migration, and apoptosis were measured by methyl thiazol tetrazolium assay, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, Transwell migration, wound healing, and flow cytometry analysis. A mouse xenograft model was used to evaluate tumor formation in vivo. Telocinobufagin was found to suppress proliferation and metastasis and induce apoptosis in human NSCLC cells. Moreover, telocinobufagin was able to significantly inhibit STAT3 phosphorylation at tyrosine 705 (Y705) and its downstream targets. Additionally, telocinobufagin also impaired the IL-6-induced nuclear translocation of STAT3. Consistent with the in vitro experiments, telocinobufagin reduced the A549 xenograft tumor burden and the levels of P-STAT3Y705, MCL1, BCL2, and cleaved PARP1 in vivo. These results support telocinobufagin as a promising STAT3 signaling inhibitor candidate for the treatment of NSCLC patients.

Fault Diagnosis Method Based on AUPLMD and RTSMWPE for a Reciprocating Compressor Valve.

In order to effectively extract the key feature information hidden in the original vibration signal, this paper proposes a fault feature extraction method combining adaptive uniform phase local mean decomposition (AUPLMD) and refined time-shift multiscale weighted permutation entropy (RTSMWPE). The proposed method focuses on two aspects: solving the serious modal aliasing problem of local mean decomposition (LMD) and the dependence of permutation entropy on the length of the original time series. First, by adding a sine wave with a uniform phase as a masking signal, adaptively selecting the amplitude of the added sine wave, the optimal decomposition result is screened by the orthogonality and the signal is reconstructed based on the kurtosis value to remove the signal noise. Secondly, in the RTSMWPE method, the fault feature extraction is realized by considering the signal amplitude information and replacing the traditional coarse-grained multi-scale method with a time-shifted multi-scale method. Finally, the proposed method is applied to the analysis of the experimental data of the reciprocating compressor valve; the analysis results demonstrate the effectiveness of the proposed method.

Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway.

Colorectal cancer (CRC) accounts for about 10% of all annually diagnosed cancers and cancer-related deaths worldwide. STAT3 plays a vital role in the occurrence and development of tumours. Gracillin has shown a significant antitumour activity in tumours, but its mechanism remains unknown. The human CRC cell lines HCT116, RKO, and SW480 and immunodeficient mice were used as models to study the effects of gracillin on cell proliferation, migration and apoptosis. These were evaluated by cell viability, colony formation, wound-healing migration and cell apoptosis assays. Luciferase reporter assay, and immunostaining and western blot analyses were used to explore the specific mechanism through which gracillin exerts its effects. Gracillin significantly reduces viability and migration and stimulates apoptosis in human CRC cells. It also significantly inhibits tumour growth with no apparent physiological toxicity in animal model experiments. Moreover, gracillin is found to inhibit STAT3 phosphorylation and STAT3 target gene products. In addition, gracillin inhibits IL6-induced nuclear translocation of P-STAT3. Gracillin shows potent efficacy against CRC by inhibiting the STAT3 pathway. It should be further explored as a unique STAT3 inhibitor for the treatment of CRC.

PET Study of Sphingosine-1-phosphate Receptor 1 Expression in Response to S. aureus Infection.

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in S. aureus-infected mice. A rodent local muscle bacterial infection model was developed by injecting S. aureus to the lower hind limb of Balb/c mice. The changes of S1PR1 expression in response to bacterial infection and blocking treatment were assessed using ex vivo biodistribution and in vivo positron emission tomography (PET) after intravenous injection of an S1PR1-specific radiotracer [18F]TZ4877. The specificity of [18F]TZ4877 was assessed using S1PR1-specific antagonist, NIBR-0213, and S1PR1-specific DsiRNA pretreated the animals. Immunohistochemical studies were performed to confirm the increase of S1PR1 expression in response to infection. Ex vivo biodistribution data showed that the uptake of [18F]TZ4877 was increased 30.6%, 54.3%, 74.3%, and 115.3% in the liver, kidney, pancreas, and thymus of the infected mice, respectively, compared to that in normal control mice, indicating that S1PR1 is involved in the early immune response to bacterial infection. NIBR-0213 or S1PR1-specific DsiRNA pretreatment reduced the tissue uptake of [18F]TZ4877, suggesting that uptake of [18F]TZ4877 is specific. Our PET/CT study data also confirmed that infected mice have increased [18F]TZ4877 uptake in several organs comparing to that in normal control mice. Particularly, compared to control mice, a 39% increase of [18F]TZ4877 uptake was observed in the infected muscle of S. aureus mice, indicating that S1PR1 expression was directly involved in the inflammatory response to infection. Overall, our study suggested that S1PR1 plays an important role in the early immune response to bacterial infection. The uptake of [18F]TZ4877 is tightly correlated with the S1R1 expression in response to S. aureus infection. PET with S1PR1-specific radiotracer [18F]TZ4877 could provide a noninvasive tool for detecting the early S1PR1 immune response to infectious diseases.

Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway.

BACKGROUND: Cyclin-dependent kinase 9 (CDK9) is a promising prognostic marker and therapeutic target in cancers. Bufalin is an effective anti-tumour agent; however, the clinical application of bufalin is limited due to its high toxicity. Acetyl-bufalin, the bufalin prodrug, was designed and synthesised with higher efficiency and lower toxicity. METHODS: Three non-small-cell lung cancer (NSCLC) cell lines, a xenograft model and a patient-derived xenograft (PDX) model were used to examine the effects of acetyl-bufalin. CDK9/STAT3 involvement was investigated by knockdown with siRNA, proteome microarray assay, western blot analysis and co-immunoprecipitation experiments. Acute toxicity test and pharmacokinetics (PK) study were conducted to assess the safety and PK. The human NSCLC tissues were analysed to verify high CDK9 expression. RESULTS: We showed that CDK9 induced NSCLC cell proliferation and that this effect was associated with STAT3 activation, specifically an increase in STAT3 phosphorylation and transcription factor activity. Acetyl-bufalin is an effective and safety inhibitor of the CDK9/STAT3 pathway, leading to the impediment of various oncogenic processes in NSCLC. Molecular docking and high-throughput proteomics platform analysis uncovered acetyl-bufalin directly binds to CDK9. Consequently, acetyl-bufalin impaired the complex formation of CDK9 and STAT3, decreased the expressions of P-STAT3, and transcribed target genes such as cyclin B1, CDC2, MCL-1, Survivin, VEGF, BCL2, and it upregulated the expression levels of BAX and caspase-3 activity. Acetyl-bufalin inhibited tumour growth in NSCLC xenograft and PDX models. CONCLUSIONS: Acetyl-bufalin is a novel blocker of the CDK9/STAT3 pathway thus may have potential in therapy of NSCLC and other cancers.

CircRNA pappalysin 1 facilitates prostate cancer development through miR-515-5p/FKBP1A axis.

The role of circular RNA (circRNA) pappalysin 1 (circ-PAPPA; hsa_circ_0088233) in prostate cancer (PCa) cells was explored in the current study. Circ-PAPPA abundance was markedly enhanced in PCa. Circ-PAPPA interference restrained cell viability, proliferation, motility and glycolysis while elevated the apoptosis rate of PCa cells. Circ-PAPPA negatively regulated microRNA-515-5p (miR-515-5p) abundance. MiR-515-5p silencing largely diminished circ-PAPPA knockdown-mediated effects in PCa cells. MiR-515-5p directly bound to FKBP prolyl isomerase 1A (FKBP1A). MiR-515-5p overexpression-mediated impacts were partly counteracted by FKBP1A overexpression. Circ-PAPPA silencing reduced FKBP1A protein level partly by elevating miR-515-5p expression. Circ-PAPPA knockdown significantly restrained the tumour growth in vivo. Circ-PAPPA elevated the malignant phenotypes of PCa cells by sequestering miR-515-5p to induce the expression of FKBP1A.

Fault Feature Extraction for Reciprocating Compressors Based on Underdetermined Blind Source Separation.

In practical engineering applications, the vibration signals collected by sensors often contain outliers, resulting in the separation accuracy of source signals from the observed signals being seriously affected. The mixing matrix estimation is crucial to the underdetermined blind source separation (UBSS), determining the accuracy level of the source signals recovery. Therefore, a two-stage clustering method is proposed by combining hierarchical clustering and K-means to improve the reliability of the estimated mixing matrix in this paper. The proposed method is used to solve the two major problems in the K-means algorithm: the random selection of initial cluster centers and the sensitivity of the algorithm to outliers. Firstly, the observed signals are clustered by hierarchical clustering to get the cluster centers. Secondly, the cosine distance is used to eliminate the outliers deviating from cluster centers. Then, the initial cluster centers are obtained by calculating the mean value of each remaining cluster. Finally, the mixing matrix is estimated with the improved K-means, and the sources are recovered using the least square method. Simulation and the reciprocating compressor fault experiments demonstrate the effectiveness of the proposed method.