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Background: The importance of amino acid metabolism in multiple cancers was investigated by accumulating researches. But the role of amino acid metabolism-related genes (AAMRGs) played in the colorectal cancer (CRC) progression remains unclear. Methods: The clinical information and RNA sequencing of CRC were acquired from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases, and amino acid metabolic gene data were downloaded from a published article in the journal Cell Reports. The Cox-LASSO analysis was adopted to establish a AAMRG prognostic signature. Kaplan–Meier (K-M) survival curve and receiver operating characteristic (ROC) curve were adopted to estimate the prognostic capacity of our risk signature. RT‒qPCR was adopted to estimate the expression of AAMRGs in clinical samples. Moreover, gene set enrichment analysis (GSEA) was adopted and according to result of GSEA, further investigation was conducted in immune infiltration, somatic mutation, drug sensitivity and EMT. Result: The activity of amino acid metabolism was significantly increased in CRC. A 10-AAMRG prognostic signature was established and the CRC samples were classified into two groups (high-risk and low-risk). Risk score was analyzed to be an independent factor of CRC to affect cancer progression. The result of RT-qPCR showed that among 10 AAMRGs, the expression abundances of MRPS23 and TRAP1 in CRC tissues and adjacent normal colorectal tissues were both upregulated. According to GSEA outcomes and further analyses, significant differences were observed in immune infiltration and EMT between two risk groups. Furthermore, analysis of drug sensitivity illustrated that some chemotherapy drugs had higher IC50 values in low-risk group, including bexarotene, bicalutamide and imatinib. Conclusion: The 10-AAMRG signature we built is a prospective biomarker, which has great potentiality to predict CRC therapeutic responses and clinical prognosis.

Cuproptosis is a new form of copper-dependent programmed cell death commonly occurring within the body. There is emerging evidence indicating that cuproptosis has a significant regulatory function in the onset and progression of cancer. However, it is still unclear how cuproptosis regulates cancer and whether other genes are involved in the regulation. Using the TCGA-COAD dataset of 512 samples, we found that seven of ten cuproptosis markers showed prognostic value in colorectal cancer (CRC) using Kaplan–Meier survival analysis. Furthermore, 31 prognostic cuproptosis-related genes were identified using weighted gene co-expression network analysis and univariate Cox analysis. Subsequently, we constructed a 7-PCRG signature using least absolute shrinkage and selection operator (LASSO)–Cox regression analysis. The risk score predicting survival in patients with CRC was evaluated. Two risk groups were classified based on their risk scores. The two groups revealed a significant difference in immune cells, such as B and T cells. Furthermore, we identified differences in many immune functions and checkpoints, including CD276 and CD28. In vitro experiments showed that a hub cuproptosis-related gene, TIGD1, could significantly regulate cuproptosis in CRC after exposure to elesclomol. This study validated that cuproptosis was closely related to the progression of CRC. Seven new cuproptosis-related genes were identified, and the function of TIGD1 in cuproptosis was preliminarily understood. Since a certain concentration of copper in CRC cells is important, cuproptosis may provide a new target for cancer therapy. This study may provide novel insights into the treatment of CRC.

An asymmetric fiber-shaped supercapacitor with excellent flexibility, ultra-high energy and power density is developed, demonstrating great practical importance.

Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that circZBTB46 was significantly upregulated in AML patients and AML cells. Moreover, the expression of circZBTB46 was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of circZBTB46 inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of circZBTB46 notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, circZBTB46 upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the circZBTB46 knockdown repressed the tumor growth of AML in vivo. In conclusion, circZBTB46 protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that circZBTB46 may be a potential therapeutic target for AML.

Transcription factors are frequently aberrantly reactivated in various cancers, including colorectal cancer (CRC). However, as a transcription factor, the role of GMEB2 in cancer is still unclear, and further studies are needed. Here, we aimed to identify the function and mechanism of GMEB2 in regulating the malignant progression of CRC. GMEB2 was found to be highly expressed in online data analyses. We demonstrated that GMEB2 was markedly upregulated at both the mRNA and protein levels in CRC cells and tissues. GMEB2 knockdown inhibited CRC cell growth in vitro and in vivo. Mechanistically, as a transcription factor, GMEB2 transactivated the ADRM1 promoter to increase its transcription. Rescue experiments showed that ADRM1 downregulation partially reversed the promoting effects of GMEB2 on CRC growth in vitro. Moreover, the GMEB2/ADRM1 axis induced nuclear translocation of NF-κB, thus activating NF-κB signalling. Finally, we further revealed that YTHDF1 recognized and bound to the m

Numerous mechanisms involved in promoting cancer cell survival under nutrient starvation have been described. Long noncoding RNAs (lncRNAs) have emerged as critical players in colorectal cancer (CRC) progression, but the role of lncRNAs in the progression of CRC under nutrient starvation has not been well clarified. Here, we identified a lncRNA, LINC01615, that was significantly upregulated in response to serum starvation. LINC01615 can contribute to the adaptation of CRC cells to serum-deprived conditions and enhance cell survival under similar conditions. LINC01615 activated the pentose phosphate pathway (PPP) under serum starvation, manifested as decreased ROS production and enhanced nucleotide and lipid synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a key rate-limiting enzyme of the PPP, and LINC01615 promoted G6PD expression by competitively binding with hnRNPA1 and facilitating G6PD pre-mRNA splicing. Moreover, we also found that serum starvation led to METTL3 degradation by inducing autophagy, which further increased the stability and level of LINC01615 in a m

Use of folic acid (FA) during early pregnancy protects against birth defects. However, excess FA has shown gender-specific neurodevelopmental toxicity. Previously, we fed the mice with 2.5 times the recommended amount of FA one week prior to mating and during the pregnancy and lactation periods, and detected the activated expression of Fos and related genes in the brains of weaning male offspring, as well as behavioral abnormalities in the adults. Here, we studied whether female offspring were affected by the same dosage of FA. An open field test, three-chamber social approach and social novelty test, an elevated plus-maze, rotarod test and the Morris water maze task were used to evaluate their behaviors. RNA sequencing was performed to identify differentially expressed genes in the brains. Quantitative real time-PCR (qRT-PCR) and Western blots were applied to verify the changes in gene expression. We found increased anxiety and impaired exploratory behavior, motor coordination and spatial memory in FA-exposed females. The brain transcriptome revealed 36 up-regulated and 79 down-regulated genes in their brains at weaning. The increase of Tlr1; Sult1a1; Tph2; Acacb; Etnppl; Angptl4 and Apold1, as well as a decrease of Ppara mRNA were confirmed by qRT-PCR. Among these genes; the mRNA levels of Etnppl; Angptl4andApold1 were increased in the both FA-exposed female and male brains. The elevation of Sult1a1 protein was confirmed by Western blots. Our data suggest that excess FA alteres brain gene expression and behaviors in female offspring, of which certain genes show apparent gender specificity.

The RNA binding protein PTBP3 was recently reported to play a critical role in multiple cancers, and the molecular mechanisms involved RNA splicing, 3′ end processing and translation. However, the role of PTBP3 in colorectal cancer (CRC) remains poorly explored. Herein, PTBP3 was upregulated in CRC and associated with a poor prognosis. PTBP3 knockdown in colorectal cancer cell lines restricted CRC proliferative capacities in vitro and in vivo. Mechanistically, PTBP3 regulated the expression of the E3 ubiquitin ligase UBE4A by binding the 3′ UTR of its mRNA, preventing its degradation. UBE4A participated in P53 degradation, and PTBP3 knockdown in colorectal cancer cell lines showed increased P53 expression. UBE4A overexpression rescued PTBP3 knockdown-induced inhibition of CRC cell proliferation and P53 expression. Our results demonstrated that PTBP3 plays an essential role in CRC cell proliferation by stabilizing UBE4A to regulate P53 expression and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

Necroptosis is a newly defined form of programmed cell death that plays an important role in cancers. However, necroptosis-related lncRNAs (NRLs) involved in colorectal cancer (CRC) have not yet been thoroughly studied. Methods: In this study, a 4-NRL model was developed based on the least absolute shrinkage and selection operator (LASSO) algorithm. A series of informatic, in vitro and in vivo analyses were applied to validate the prognostic value of the model and the potential function of the hub lncRNA MYOSLID. Results: The model exhibited an excellent capacity for the prediction of overall survival and other clinicopathological features of CRC patients using Kaplan–Meier (K–M) survival curves and receiver operating characteristic (ROC) curves. Furthermore, a significant difference in the levels of immune cells, such as CD4 memory T cells and activated mast cells, between two risk groups was observed. The low-risk patients had a higher expression of immune checkpoints, such as PDCD1 (PD-1) and CD274 (PD-L1). The levels of MYOSLID, a hub lncRNA in our model, were higher in CRC tissues than in normal tissues. Knockdown of MYOSLID induced necroptosis and inhibited the proliferation of CRC cells in vitro and in vivo. Interestingly, knockdown of MYOSLID also increased the percentage of CD4+ and CD8+ T cells in subcutaneously transplanted tumours. Conclusion: Our model is a promising biomarker that can be used to predict clinical outcomes in CRC patients, and MYOSLID plays an important role in regulating necroptosis and immune cell infiltration in CRC.

Background Colorectal cancer (CRC) is the most common malignancy worldwide and has become the second leading cause of cancer-related death worldwide. The RNA-binding protein polypyrimidine tract-binding protein 3 (PTBP3) was recently reported to play a critical role in multiple cancers, and its molecular mechanisms involve RNA splicing, 3′ end processing and translation. However, the role of PTBP3 in CRC is unclear. Methods We analyzed the expression levels of PTPB3 using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and clinical tissues. The effect of PTBP3 on CRC cell proliferation was measured by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and tumor xenograft assays. A series of experiments were conducted to reveal the mechanisms by which PTBP3 promotes CRC proliferation. Results We showed that PTBP3 was upregulated in CRC and associated with a poor prognosis. Knockdown of PTBP3 in CRC cell lines restricted CRC proliferative capacities in vitro and in vivo. Mechanistically, we found that PTBP3 regulated the expression of the E3 ubiquitin ligase ubiquitination factor E4A (UBE4A) by binding the 3' untranslated region (UTR) of its mRNA, thereby preventing its degradation. We also discovered that UBE4A participated in the degradation of P53, and knockdown of PTBP3 in CRC cell lines increased P53 expression. Overexpression of UBE4A rescued PTBP3 knockdown-induced inhibition of CRC cell proliferation and P53 expression. Conclusions PTBP3 plays an essential role in CRC cell proliferation by stabilizing UBE4A to regulate P53 expression and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer but have not been fully clarified. Therefore, our goal was to identify the key miRNA–mRNA regulatory network in gastric cancer by utilizing a variety of bioinformatics analyses and experiments. A total of 242 miRNAs and 1080 genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Then, survival-related differentially expressed miRNAs and their differentially expressed target genes were screened. Twenty hub genes were identified from their protein–protein interaction network. After weighted gene co-expression network analysis was conducted, we selected miR-137-3p and its target gene, COL5A1, for further research. We found that miR-137-3p was significantly downregulated and that overexpression of miR-137-3p suppressed the proliferation, invasion, and migration of gastric cancer cells. Furthermore, we found that its target gene, COL5A1, could regulate the expression of another hub gene, FSTL1, by sponging miR-137-3p, which was confirmed by dual-luciferase reporter assays. Knockdown of COL5A1 inhibited the proliferation, invasion, and migration of gastric cancer cells, which could be rescued by the miR-137-3p inhibitor or overexpression of FSTL1. Ultimately, bioinformatics analyses showed that the expression of FSTL1 was highly correlated with immune infiltration.

Reducing friction and wear is a long-standing concern for machinery. Bulk solid lubricants have been widely adopted to address the tribological challenges at the macroscale, yet their implementation is relatively limited for small-scale applications. Recently, the emergence of two-dimensional (2D) materials brings a new horizon of a range of ultrathin solid lubricants for micro- and nanoscale sliding interfaces. Using ball-on-disk friction tests, we found that monolayer MoS2 possessed an outstanding lubrication performance when the normal load was below a threshold, beyond which wear set in. Further scratch tests on monolayer MoS2 showed that this critical normal load was significantly affected by the residual strain in MoS2. As revealed by finite-element simulations, MoS2 failed primarily because of in-plane stretching during tribological sliding, and the tensile residual strain would add to the in-plane strain inside MoS2, resulting in a noticeably weaker antiwear performance. This work provides guideli...

Low-dimensional semiconductors provide promising ultrathin channels for constructing more-than-Moore devices. However, the prominent contact barriers at the semiconductor-metal electrodes interfaces greatly limit the performance of the obtained devices. Here, a chemical approach is developed for the construction of p-type field-effect transistors (FETs) with low contact barriers by achieving the simultaneous synthesis and integration of 2D PdTe

Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01318-6.

Additional file 4. Network of circRNA-miRNA-mRNA interactions in colorectal cancer.

Background The double lumen endotracheal tube (DLT) is the most widely-used device for single lung ventilation in current thoracic anesthesia practice. In recent years, the routine application of the videolaryngoscope for single lumen endotracheal intubation has increased; nevertheless there are few studies of the use of the videolaryngoscope for DLT. We wondered whether there were benefits to using the videolaryngoscope for DLT placement in patients with predicted normal airways. Therefore, this study was designed to compare the performances of the GlideScope®, the C-MAC®(D) videolaryngoscope and the Macintosh laryngoscope in DLT intubation. Methods This was a randomized, controlled, prospective study. We randomly allocated 90 adult patients with predicted normal airways into three groups. All patients underwent routine anesthesia using different laryngoscopes according to group allocation. We compared DLT insertion times, first-pass success rates, numerical rating scales (NRS) of DLT delivery and DLT insertion, Cormack-Lehane degrees (C/L), hemodynamic changes and incidences of intubation complications. All outcomes were analyzed using SPSS13.0. Results Compared with the GlideScope, the Macintosh gave shorter times for DLT insertion (median: 96 (IQR: 51 [min–max: 62–376] s vs 73 (26 [48–419] s, p = 0.003); however, there was no difference between the Macintosh and C-MAC(D) (p = 0.610). The Macintosh had a significantly higher successful first attempt rate than did the GlideScope or C-MAC(D) (p = 0.001, p = 0.028, respectively). NRS of DLT delivery and insertion were significantly lower in the Macintosh than in the others (p p > 0.05). There were no significant differences in DLT misplacement, fiberoptic time or hemodynamic changes among the groups. Conclusions Compared with the Macintosh laryngoscope, the GlideScope® and C-MAC®(D) videolaryngoscopes may not be recommended as the first choice for routine DLT intubation in patients with predicted normal airways. Trial registration The study was prospectively registered at the Chinese Clinical Trial Registry (no. ChiCTR1900025718); principal investigator: Z.L.H.; date of registration: September 6, 2019.

Background Double lumen endotracheal tube (DLT) is the most widely used method for lung isolation in current thoracic anesthesia practice. In recent years, the routine application of videolaryngoscope for tracheal intubation has gradually increased, but there are still few related reports. We doubted whether we could get benefits from applying the videolaryngoscope for double-lumen tracheal tube placement in patients with predicted normal airways. Therefore, this study was designed to compare the clinical performance of GlideScope ® , C-MAC ® (D) videolaryngoscope and Macintosh laryngoscope in DLT intubation. Methods 90 adult patients with no predictors for difficult airways were allocated randomly into three groups. All the patients were anesthsized by a routine anesthesia process with different laryngoscopes according to the result of allocation. We accessed DLT insertion time, first-pass success rate, numerical rating scale (NRS) of DLT delivery, NRS of DLT insertion and Cormack-Lehane degree(C/L degree). The hemodynamic change and the incidence of intubation complications were also recorded. Results Compared with GlideScope, Macintosh resulted in shorter time for DLT insertion (median:96(IQR:51[min-max:62–376]s v 73(26[48-419]s, p=0.003), but there was no difference between Macintosh and C-MAC(D) (p=0.610). As for the success at the first attempt, Macintosh was significantly associated with higher successful rate compared with GlideScope and C-MAC(D) (p=0.001, p=0.028, respectively). NRS of DLT delivery and NRS of DLT insertion were significantly lower in Macintosh group than others (p0.05, respectively). There were no statistical difference about DLT misplacement, fibreoptic time and hemodynamic changes among three groups. Conclusions GlideScope ® and C-MAC ® (D) videolaryngoscopes may not be recommended as the first choice for routine DLT intubation in patients with predicted normal airways.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) with layered structures provide a unique platform for exploring the effect of number of layers on their fundamental properties. However, the thickness scaling effect on the chemical properties of these materials remains unexplored. Here, we explored the chemically induced phase transition of 2D molybdenum disulfide (MoS2) from both experimental and theoretical aspects and observed that the critical electron injection concentration and the duration required for the phase transition of 2D MoS2 increased with decreasing number of layers. We further revealed that the observed dependence originated from the layer-dependent density of states of 2H-MoS2, which results in decreasing phase stability for 2H-MoS2 with increasing number of layers upon electron doping. Also, the much larger energy barrier for the phase transition of monolayer MoS2 induces the longer reaction time required for monolayer MoS2 as compared to multilayer MoS2. The layer-dependen...

Eutectic Gallium-Indium (EGaIn) is a promising technique to fabricate self-assembled monolayers (SAMs)-based molecular devices. However, several abnormal signals had been reported in previous measurements on the as-fabricated devices, like the offset of zero-bias current and others. To date, the limited study has been taken to explore the origin of the offset, which prevents the understanding of electrical transport through large-area molecular tunneling junctions, and hinders the development of high-performance devices. To explore the offset of zero-bias current, we built a new EGaIn automatic instrument platform, which allowed a systematic study on the electrical behavior of SAMs of n-alkanethiolate (n = 14, 16, 18). The measurements showed that the ambient water affected charge transport through as-fabricated molecular junctions. With the presence of water, a primary cell was established at the interface between SAMs and EGaIn/GaOx, which generated an internal potential and caused the offset of zero-bias current when the geometry contact area of the molecular junction is smaller than 600 μm2.

Research on water purification has recently revolved around nanomaterials because of their large specific surface area. However, there are still some problems associated with the preparation, application, and recovery of nanomaterials. Herein, we report for the first time a novel approach for one-step synthesis of porous hybrid fibers (PHFs), which can be used as an effective adsorbent for dye removal from polluted water. A low-cost biopolymer cellulose was chosen as the matrix of the fibers, whereas a NaOH solution was applied as the coagulation bath for the cellulose spinning dope that contained a certain amount of FeCl3. The obtained Fe(OH)3@Cellulose PHFs exhibited a multiscaled pore structure, with the in situ generated Fe(OH)3 nanoparticles uniformly distributed on the regenerated cellulose nanofibrous network of the fibers. These structural attributes are quite advantageous for an efficient adsorbent. The maximum Congo red removal capacity of the Fe(OH)3@Cellulose PHFs reached 689.65 mg/g, which wa...

The conventional strategies employed for the synthesis of hollow nanofibers (HNFs) require either multistep treatments or special design of the equipment. An additional annealing process is always required, which inevitably consumes more energy and raises the manufacturing cost. In addition, the annealing process may also cause a waste of the matrix materials and the release of toxic gases. Herein, we report for the first time a novel one-step synthesis of hollow hybrid nanofibers via electrospinning. Cellulose was chosen as the polymer matrix, and Fe(OH)3 nanoparticles were grown in situ on the nanofibers during electrospinning. There was no need to remove cellulose to create the hollow nanofiber structure. This can significantly simplify the fabrication process without any negative influence to the air. The obtained Fe(OH)3@cellulose HNF membranes exhibited great mechanical properties and an extremely high water flux of 11 200 L m–2 h–1 bar–1. They could effectively remove various pollutants in water, i...