A two-step method of cyclolinopeptide (linusorb) preparation from flaxseed cake via dry-screening.

Linusorbs (LO), cyclolinopeptides, are a group of cyclic hydrophobic peptides and considered a valuable by-product of flaxseed oil due to numerous health benefits. Currently applied acetone or methanol extraction could contaminate the feedstocks for further food-grade application. Using flaxseed cake as feedstock, this study established a practical method for preparing LO from pressed cake. Firstly, LO composition of 15 flaxseed cultivars was analyzed. Next, cold-pressed cake was milled and screened mechanically. The kernel and hull fractions were separated based on the disparity of their mechanical strength. Monitored by hyperspectral fluorescence, the LO-enriched kernel fraction separated from cold-pressed flaxseed cake was further used as feedstock for LO production. After ethanol extraction, partition, and precipitation, LOs were extracted from cold-pressed flaxseed cake with a purity of 91.4%. The proposed method could serve as feasible flaxseed cake valorization strategy and enable the preparation of other polar compounds such as flax lignan and mucilage.

Predictive significance of glycolysis-associated lncRNA profiles in colorectal cancer progression.

BACKGROUND: The Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs). METHODS: Utilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters. RESULTS: The prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A - AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect. CONCLUSIONS: Our research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A - AS1 in the Warburg effect in colorectal cancer.

Synergistic targeting of TrxR1 and ATM/AKT pathway in human colon cancer cells.

Thioredoxin reductase 1 (TrxR1) has emerged as a promising target for cancer therapy. In our previous research, we discovered several new TrxR1 inhibitors and found that they all have excellent anti-tumor activity. At the same time, we found these TrxR1 inhibitors all lead to an increase in AKT phosphorylation in cancer cells, but the detailed role of AKT phosphorylation in TrxR1 inhibitor-mediated cell death remains unclear. In this study, we identified the combination of AKT and TrxR1 inhibitor displayed a strong synergistic effect in colon cancer cells. Furthermore, we demonstrated that the synergistic effect of auranofin (TrxR1 inhibitor) and MK-2206 (AKT inhibitor) was caused by ROS accumulation. Importantly, we found that ATM inhibitor KU-55933 can block the increase of AKT phosphorylation caused by auranofin, and exhibited a synergistic effect with auranofin. Taken together, our study demonstrated that the activation of ATM/AKT pathway is a compensatory mechanism to cope with ROS accumulation induced by TrxR1 inhibitor, and synergistic targeting of TrxR1 and ATM/AKT pathway is a promising strategy for treating colon cancer.

LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Rolapitant treats lung cancer by targeting deubiquitinase OTUD3.

BACKGROUND: Lung cancer is cancer with the highest morbidity and mortality in the world and poses a serious threat to human health. Therefore, discovering new treatments is urgently needed to improve lung cancer prognosis. Small molecule inhibitors targeting the ubiquitin-proteasome system have achieved great success, in which deubiquitinase inhibitors have broad clinical applications. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. RESULTS: In this study, we identified a small molecule inhibitor of OTUD3, Rolapitant, by computer-aided virtual screening and biological experimental verification from FDA-approved drugs library. Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3. Quantitative proteomic profiling indicated that Rolapitant significantly upregulated the expression of death receptor 5 (DR5). Rolapitant also promoted lung cancer cell apoptosis through upregulating cell surface expression of DR5 and enhanced TRAIL-induced apoptosis. Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis. In the vivo assays, Rolapitant suppressed the growth of lung cancer xenografts in immunocompromised mice at suitable dosages without apparent toxicity. CONCLUSION: In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer.

Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells.

Lung cancer is one of the most lethal diseases in the world. Although there has been significant progress in the treatment of lung cancer, there is still a lack of effective strategies for advanced cases. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, has achieved much attention due to its antitumor properties. Nevertheless, the use of lenvatinib is restricted by the characteristics of poor efficacy and drug resistance. In this study, we assessed the effectiveness of lenvatinib combined with thioredoxin reductase 1 (TrxR1) inhibitors in human lung cancer cells. Our results indicate that the combination therapy involving TrxR1 inhibitors and lenvatinib exhibited significant synergistic antitumor effects in human lung cancer cells. Moreover, siTrxR1 also showed significant synergy with lenvatinib in lung cancer cells. Mechanically, we demonstrated that ROS accumulation significantly contributes to the synergism between lenvatinib and TrxR1 inhibitor auranofin. Furthermore, the combination of lenvatinib and auranofin can activate endoplasmic reticulum stress and JNK signaling pathways to achieve the goal of killing lung cancer cells. Importantly, combination therapy with lenvatinib and auranofin exerted a synergistic antitumor effect in vivo. To sum up, the combination therapy involving lenvatinib and auranofin may be a potential strategy for treating lung cancer.

Dynamic-group-aware networks for multi-agent trajectory prediction with relational reasoning.

Demystifying the interactions among multiple agents from their past trajectories is fundamental to precise and interpretable trajectory prediction. However, previous works mainly consider static, pairwise interactions with limited relational reasoning. To more comprehensively model interactions and reason relations, we propose DynGroupNet, a dynamic-group-aware network, which (i) models time-varying interactions in highly dynamic scenes; (ii) captures both pairwise and group-wise interactions; and (iii) reasons both interaction strength and category without direct supervision. Based on DynGroupNet, we further design a prediction system to forecast socially plausible trajectories with dynamic relational reasoning. The proposed prediction system leverages the Gaussian mixture model, multiple sampling and prediction refinement to promote prediction diversity for multiple future possibilities capturing, training stability for efficient model learning and trajectory smoothness for more realistic predictions, respectively. The proposed complex interaction modeling of DynGroupNet, future diversity capturing, efficient model training and trajectory smoothing of prediction system together to promote more accurate and plausible future predictions. Extensive experiments show that: (1) DynGroupNet can capture time-varying group behaviors, infer time-varying interaction category and interaction strength during prediction; (2) DynGroupNet significantly outperforms the state-of-the-art trajectory prediction methods by 28.0%, 34.9%, 13.0% in FDE on the NBA, NFL and SDD datasets.

Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells.

Colon cancer is a major cause of cancer-related death. Despite recent improvements in the treatment of colon cancer, new strategies to improve the overall survival of patients are urgently needed. Heat shock protein 90 (HSP90) is widely recognized as a promising target for treating various cancers, including colon cancer. However, no HSP90 inhibitor has been approved for clinical use due to limited efficacy. In this study, we evaluated the antitumor activities of HSP90 inhibitors in combination with piperlongumine in colon cancer cells. We show that combination treatment with HSP90 inhibitors and piperlongumine displayed strong synergistic interaction in colon cancer cells. These agents synergize by promoting ER stress, JNK activation, and DNA damage. This process is fueled by oxidative stress, which is caused by the accumulation of reactive oxygen species. These studies nominated piperlongumine as a promising agent for HSP90 inhibitor-based combination therapy against colon cancer.

Collaborative Uncertainty Benefits Multi-Agent Multi-Modal Trajectory Forecasting.

In multi-modal multi-agent trajectory forecasting, two major challenges have not been fully tackled: 1) how to measure the uncertainty brought by the interaction module that causes correlations among the predicted trajectories of multiple agents; 2) how to rank the multiple predictions and select the optimal predicted trajectory. In order to handle the aforementioned challenges, this work first proposes a novel concept, collaborative uncertainty (CU), which models the uncertainty resulting from interaction modules. Then we build a general CU-aware regression framework with an original permutation-equivariant uncertainty estimator to do both tasks of regression and uncertainty estimation. Furthermore, we apply the proposed framework to current SOTA multi-agent multi-modal forecasting systems as a plugin module, which enables the SOTA systems to: 1) estimate the uncertainty in the multi-agent multi-modal trajectory forecasting task; 2) rank the multiple predictions and select the optimal one based on the estimated uncertainty. We conduct extensive experiments on a synthetic dataset and two public large-scale multi-agent trajectory forecasting benchmarks. Experiments show that: 1) on the synthetic dataset, the CU-aware regression framework allows the model to appropriately approximate the ground-truth Laplace distribution; 2) on the multi-agent trajectory forecasting benchmarks, the CU-aware regression framework steadily helps SOTA systems improve their performances. Especially, the proposed framework helps VectorNet improve by 262 cm regarding the Final Displacement Error of the chosen optimal prediction on the nuScenes dataset; 3) in multi-agent multi-modal trajectory forecasting, prediction uncertainty is proportional to future stochasticity; 4) the estimated CU values are highly related to the interactive information among agents. The proposed framework can guide the development of more reliable and safer forecasting systems in the future.

Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex.

PURPOSE: High-risk neuroblastoma (NB) still has an unfavorable prognosis and inducing NB differentiation is a potential strategy in clinical treatment, yet underlying mechanisms are still elusive. Here we identify TRIM24 as an important regulator of NB differentiation. METHODS: Multiple datasets and clinical specimens were analyzed to define the role of TRIM24 in NB. The effects of TRIM24 on differentiation and growth of NB were determined by cell morphology, spheres formation, soft agar assay, and subcutaneous xenograft in nude mice. RNA-Seq and qRT-PCR were used to identify genes and pathways involved. Mass spectrometry and co-immunoprecipitation were used to explore the interaction of proteins. RESULTS: Trim24 is highly expressed in spontaneous NB in TH-MYCN transgenic mice and clinical NB specimens. It is associated with poor NB differentiation and unfavorable prognostic. Knockout of TRIM24 in neuroblastoma cells promotes cell differentiation, reduces cell stemness, and inhibits colony formation in soft agar and subcutaneous xenograft tumor growth in nude mice. Mechanistically, TRIM24 knockout alters genes and pathways related to neural differentiation and development by suppressing LSD1/CoREST complex formation. Besides, TRIM24 knockout activates the retinoic acid pathway. Targeting TRIM24 in combination with retinoic acid (RA) synergistically promotes NB cell differentiation and inhibits cell viability. CONCLUSION: Our findings demonstrate that TRIM24 is critical for NB differentiation and suggest that TRIM24 is a promising therapeutic target in combination with RA in NB differentiation therapy.

Tailored Dynamic Viscoelasticity of Polyurethanes Based on Different Diols.

The development of damping and tire materials has led to a growing need to customize the dynamic viscoelasticity of polymers. In the case of polyurethane (PU), which possesses a designable molecular structure, the desired dynamic viscoelasticity can be achieved by carefully selecting flexible soft segments and employing chain extenders with diverse chemical structures. This process involves fine-tuning the molecular structure and optimizing the degree of micro-phase separation. It is worth noting that the temperature at which the loss peak occurs increases as the soft segment structure becomes more rigid. By incorporating soft segments with varying degrees of flexibility, the loss peak temperature can be adjusted within a broad range, from -50 °C to 14 °C. Furthermore, when the molecular structure of the chain extender becomes more regular, it enhances interaction between the soft and hard segments, leading to a higher degree of micro-phase separation. This phenomenon is evident from the increased percentage of hydrogen-bonding carbonyl, a lower loss peak temperature, and a higher modulus. By modifying the molecular weight of the chain extender, we can achieve precise control over the loss peak temperature, allowing us to regulate it within the range of -1 °C and 13 °C. To summarize, our research presents a novel approach for tailoring the dynamic viscoelasticity of PU materials and thus offers a new avenue for further exploration in this field.

Ozone micro-bubble aeration using the ceramic ultrafiltration membrane with superior oxidation performance for 2, 4-D elimination.

Micro-bubble aeration is an efficient way to promote ozonation performance, but the technology is challenged by extensive energy cost. Here, a ceramic ultrafiltration membrane was used to achieve ozone micro-bubble (0-80 µm) aeration in a simple way at gaseous pressures of 0.14-0.19 MPa. Compared with milli-bubble aeration, micro-bubble aeration increased the equilibrium aquatic O3 concentrations by 1.53-3.25 times and apparent O3 transfer rates by 3.12-3.35 times at pH 5.0-8.0. Consequently, the •OH yield was 2.67-3.54 times via faster O3 transfer to the aquatic solution followed by decomposition rather than interfacial reaction. Ozone micro-bubble aeration outperformed milli-bubble aeration, with the degradation kinetics of 2,4-D being 3.08-4.36 times higher. Both O3-oxidation and •OH oxidation were important to the promotion with the contributions being 35.8%-45.9% and 54.1%-64.2%, respectively. The operational and water matric conditions influenced the oxidation performance via both O3 oxidation and •OH oxidation, which is reported for the first time. In general, the ceramic membrane offered a low-energy approach of ozone micro-bubble aeration for efficient pollutant degradation. The O3 oxidation and •OH oxidation were proportionally promoted by ozone micro-bubble due to O3 transfer enhancement. Thus, the promotive mechanism can be interpreted as the synchronous enchantment on ozone exposure and •OH exposure for the first time.

Simultaneous passivation on both A and X sites of halogen perovskite with magnesium benzoate.

Surface modification engineering is a well-known effective passivation method for making efficient and stable perovskite solar cells (PSCs). However, to our knowledge, little attention has been paid to simultaneously passivating the A and X sites of halogen perovskites. Herein, we introduced an organometallic salt (C6H5COO)2Mg (MgBEN) as a passivator, and as a result, the C6H5COOMg+ passivates the A site and C6H5COO- the X site on the perovskite layer, significantly reducing the trap-state density and nonradiative recombination. Moreover, the modification induces the perovskite film quality to improve, which may decrease the charge accumulation and facilitate carrier transport. By optimizing the concentration of the MgBEN, the perovskite film showed an increased grain size (from 1.18 µm to 1.61 µm), and the best device exhibited an enhanced power conversion efficiency (PCE) of 22.24%. Meanwhile, the device after modification performed with good long-term stability.

The Relationships of Creative Coping and College Students' Achievement Emotions and Academic Stress: The Mediating Role of Psychological Capital.

Creative coping is the use of creativity as a positive strategy when facing stress. The existing empirical investigation of creative coping is scarce, particularly in the field of educational psychology. The present study aims to explore the relationships of college students' creative coping and their achievement emotions and academic stress as well as the underlying mechanism. The sample included 780 Chinese college students. The Creative Coping Scale, Positive Psychological Capital Questionnaire, Learning Stress Inventory for College Students, and the short version of the Achievement Emotions Questionnaire were used. Statistical results showed that creative coping was positively related with students' positive achievement emotions and negatively related with negative achievement emotions, but insignificantly with academic stress. Moreover, psychological capital played a mediating role in the relationship between creative coping and achievement emotions and in the relationship between creative coping and academic stress with a suppression effect.

Aqueous extract of Paeoniae Radix Alba (Paeonia lactiflora Pall.) ameliorates DSS-induced colitis in mice by tunning the intestinal physical barrier, immune responses, and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease, the pathogenesis of which is strongly associated with the compromised intestinal barrier. Paeoniae Radix Alba (PRA), the root of Paeonia lactiflora Pall., is a well-known traditional Chinese medicine and an adaptogen used in Hozai, exhibiting appreciable anti-inflammatory and immunomodulatory activity. Nevertheless, the role and mechanism of PRA in UC have yet to be elucidated. AIM OF THE STUDY: This study was set out to examine the ameliorative effects of the aqueous extract of PRA (i.e., PRA dispensing granule, PRADG) on dextran sulfate sodium (DSS)-induced colitis. MATERIALS AND METHODS: The chemical components of PRADG was analyzed by HPLC. Colitis model mice were induced by free access to water containing 2.5% DSS for 10 consecutive days, and concurrently, PRADG (0.1025 and 0.41 g/kg) or Salazosulfapyridine (SASP, 450 mg/kg) was given orally from day 1-10. Body weight, disease activity index (DAI), colon length, histologic scoring, and inflammatory response were assessed. Additionally, IL-23/IL-17 axis and tight junction (TJ) proteins, as well as gut microbiota were also investigated under the above-mentioned regimen. RESULTS: Eight main chemical constituents of CPT were revealed with HPLC analysis. Noticeably, PRADG could effectively lower body weight loss as well as DAI scores, alleviate colon shortening, and reduce the levels of proinflammatory cytokines in mice with colitis. Further exploration found that increment of TJ proteins expression (ZO-1, occludin and claudin-1) and inhibition of IL-23/IL-17 axis-modulated inflammation were observed in PRADG-treated mice. Additionally, the diversity of gut microbiota and the relative abundance of beneficial bacteria were increased following PRADG treatment. CONCLUSIONS: PRADG could be sufficient to ameliorate colitis by regulating the intestinal physical barrier, immune responses, and gut microbiota in mice. Our findings highlight that PRADG might be a prospective remedy for UC.

A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway.

Objective: Colorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC. Methods: Multiple datasets from the GEO database and TCGA database were utilized for bioinformatics analysis. WGCNA analyses and RRA analysis were performed to identify key genes. The COX/Lasso regression model was used to construct the recurrence model. Subsequent in vitro experiments further validated the potential role of the hub genes in CRC. Results: A comprehensive analysis was performed on multiple CRC datasets and a CRC recurrence model was constructed containing LEMD1, SERPINE1, and SIAE. After further validation in two independent databases, we selected LEMD1 for in vitro experiments and found that LEMD1 could regulate CRC cell proliferation, migration, invasion, and promote EMT transition. The Rho-GTPase pulldown experiments further indicated that LEMD1 could affect RhoA activity and regulate cytoskeletal dynamics. Finally, we demonstrated that LEMD1 promoted CRC cell migration through the RhoA/ROCK1 signaling pathway. Conclusions: In this study, a CRC relapse model consisting of LEMD1, SERPINE1, and SIAE was constructed by comprehensive analysis of multiple CRC datasets. LEMD1 could promote CRC cell migration through the RhoA/ROCK signaling pathway.

Glaucocalyxin B Attenuates Ovarian Cancer Cell Growth and Cisplatin Resistance In Vitro via Activating Oxidative Stress.

Ovarian cancer is one of the fatal gynecological cancers around the world. Cisplatin is the first-line chemotherapy drug for the clinical treatment of ovarian cancer. However, many patients with ovarian cancer are still suffering from resistance to cisplatin. Therefore, the new drug combinations or treatment strategies for ovarian cancer are urgently needed. Glaucocalyxin B (GLB), a diterpenoid isolated from the aerial parts of Rabdosia japonica, has shown antitumor activity in some tumors. However, the mechanisms by which GLB inhibits ovarian cancer remain unclear. In the present study, we showed that GLB potently inhibits ovarian cancer cell growth in a dose-dependent manner. Furthermore, we found that GLB has a notably synergistic antitumor effect with cisplatin. Mechanistically, we found that GLB enhances the sensitivity of ovarian cancer cells to cisplatin via increasing reactive oxygen species (ROS) levels, the phosphorylation of c-Jun N-terminal kinase (JNK), and DNA damage. Interestingly, a synergistic inhibitory effect of GLB with cisplatin was also observed in the cells which were resistance to cisplatin. Together, these data suggest that GLB can sensitize ovarian cancer cells to cisplatin by increasing ROS levels.

VLX1570 regulates the proliferation and apoptosis of human lung cancer cells through modulating ER stress and the AKT pathway.

The ubiquitin-proteasome system (UPS) possesses unique functions in tumorigenesis and has great potential for targeting tumours. The effectiveness of inhibitors targeting UPS in solid tumours remains to be studied. We screened a library of inhibitors targeting the ubiquitination system and found the highly potent, low-concentration inhibitor molecule VLX1570 that specifically killed lung cancer cells. VLX1570 is an inhibitor of deubiquitinating enzyme activity and has also shown potential for preclinical cancer treatment. We found that VLX1570 significantly inhibited lung cancer cells proliferation and colony formation. VLX1570 induced a G2/M cell cycle arrest by downregulating CDK1 and CyclinB1. Moreover, VLX1570 significantly promoted the mitochondrial-associated apoptosis. Mechanistically speaking, VLX1570 activated the PERK/IRE1/ATF6 pathway and induced ER stress in lung cancer cell lines. The inhibition of ER stress by tauroursodeoxycholic acid sodium or 4-phenylbutyric acid enhanced VLX1570-induced apoptosis. In addition, VLX1570 treatment led to the inactivation of Akt signalling and inhibited the proliferation of lung cancer cells by downregulating the Akt pathway. Moreover, combined treatment with VLX1570 and Afatinib or Gefitinib induced synergistic anti-lung cancer activity. Our present study demonstrated a novel therapy using VLX1570, which inhibited the proliferation and increased apoptosis in human lung cancer.

Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer.

Abnormal metabolism, including abnormal fatty acid metabolism, is an emerging hallmark of cancer. The current study sought to investigate the potential prognostic value of fatty acid metabolism-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). To this end, we obtained the gene expression data and clinical data of patients with CRC from The Cancer Genome Atlas (TCGA) database. Through gene set variation analysis (GSVA), we found that the fatty acid metabolism pathway was related to the clinical stage and prognosis of patients with CRC. After screening differentially expressed RNAs, we constructed a fatty acid metabolism-related competing endogenous RNA (ceRNA) network based on the miRTarBase, miRDB, TargetScan, and StarBase databases. Next, eight fatty acid metabolism-related lncRNAs included in the ceRNA network were identified to build a prognostic signature with Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, and a nomogram was established based on the lncRNA signature and clinical variables. The signature and nomogram were further validated by Kaplan-Meier survival analysis, Cox regression analysis, calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA). Besides, the TCGA internal and the quantitative real-time polymerase chain reaction (qRT-PCR) external cohorts were applied to successfully validate the robustness of the signature and nomogram. Finally, in vitro assays showed that knockdown of prognostic lncRNA TSPEAR-AS2 decreased the triglyceride (TG) content and the expressions of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) in CRC cells, which indicated the important role of lncRNA TSPEAR-AS2 in modulating fatty acid metabolism of CRC. The result of Oil Red O staining showed that the lipid content in lncRNA TSPEAR-AS2 high expression group was higher than that in lncRNA TSPEAR-AS2 low expression group. Our study may provide helpful information for fatty acid metabolism targeting therapies in CRC.

Factors Influencing Early Serum Uric Acid Fluctuation After Bariatric Surgery in Patients with Hyperuricemia.

PURPOSE: In the short-term after bariatric surgery, the incidence of gout flare was increased. Patients with hyperuricemia are among the high-risk group of postoperative gout attacks. The drastic fluctuation of uric acid is a risk factor for gout flare. This study aimed to explore factors that influenced the magnitudes of serum uric acid (sUA) fluctuation post-surgery in patients with hyperuricemia. MATERIALS AND METHODS: One hundred and sixty-five patients with preoperative hyperuricemia undergoing bariatric surgery were reviewed. Pre- and postoperative parameters were collected at baseline and each follow-up point. Univariable and multiple linear regression analyses were performed to explore independent factors that influenced the magnitudes of sUA change. RESULTS: The sUA significantly declined from 489.4 ± 93.7 to 372.6 ± 101.4 µmmol/L in 1 day after surgery, then increased to 531.6 ± 175.5 µmmol/L at 1-month follow-up, and then dropped to 415.2 ± 105.6 and 396.5 ± 114.2 µmmol/L at 3-month and 6-month follow-up, respectively. Preoperative estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), magnesium (Mg), sex, and the change of zinc concentration during the first month are significantly related to magnitudes of sUA fluctuation in the short-term post-surgery period. Multiple linear regression analyses showed preoperative eGFR and HbA1c independently influenced the magnitudes of sUA change at 1 day after surgery; sex, the change of zinc concentration, and HbA1c at 1-month follow-up independently influenced the magnitudes of sUA change at 1-month follow-up. CONCLUSION: Preoperative eGFR, HbA1c, sex, and the change of zinc concentration postoperative are independent factors affecting the magnitude of the fluctuation. Large-scale studies are warranted to support these findings.