TGIF2 is a potential biomarker for diagnosis and prognosis of glioma.

Background: TGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive. Methods: The expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot. Results: TGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype. Conclusion: TGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.

Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

Comprehensive analysis reveals TSPEAR as a prognostic biomarker in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors and has high morbidity and mortality rates. Previous studies have shown that TSPEAR mutations are involved in the development and progression of gastric cancer and liver cancer. However, the role of TSPEAR in CRC is still unclear. Methods: In The Cancer Genome Atlas (TCGA) database, 590 CRC patients with complete survival information were analyzed. We assessed TSPEAR expression in a pan-cancer dataset from the TCGA database. Cox regression analysis was performed to evaluate factors associated with prognosis. Enrichment analysis via the R package "clusterProfiler" was used to explore the potential function of TSPEAR. The single-sample GSEA (ssGSEA) method from the R package "GSVA" and the TIMER database were used to investigate the association between the immune infiltration level and TSPEAR expression in CRC. The R package "maftools" was used to explore the association between tumour mutation burden (TMB) and TSPEAR expression in CRC. CCK-8 assays and cell invasion assays were used to detect the effect of TSPEAR and TGIF2 on the biological behavior of CRC cells. Results: Pan-cancer analysis revealed that TSPEAR was upregulated in CRC tissues compared to normal tissues and that high TSPEAR expression was associated with poorer overall survival (OS) (p=0.0053). The expression of TSPEAR increased with increasing TNM stage, T stage, N stage, and M stage. The nomogram constructed with TSPEAR, age, and TNM stage showed better predictive value than TSPEAR, age, or TNM stage alone. Immune cell infiltration analysis revealed that high expression of TSPEAR was associated with lower immune cell infiltration. Tumor mutation burden (TMB) analysis indicated that high expression of TSPEAR was associated with lower TMB (p=0.005), and high TMB was associated with shorter OS (p=0.02). CCK-8 assays and cell invasion assays indicated that in vitro knockdown of TSPEAR inhibited the proliferation, migration, and invasion of CRC cells. In addition, TSPEAR expression may be regulated by the upstream transcription factor TGIF2. Conclusion: TSPEAR expression was higher in CRC tissues than in normal tissues. Its upregulation was significantly associated with a poor prognosis. Additionally, TSPEAR plays a significant role in tumor immunity and the biological behavior of CRC cells. Thus, TSPEAR may become a promising prognostic biomarker and therapeutic target for CRC patients.

A chiral two-dimensional perovskite-like lead-free bismuth(III) iodide hybrid with high phase transition temperature.

Bismuth(III) iodide perovskites have attracted great attention as lead-free hybrid semiconductors, but they mainly show zero- and one-dimensional structures. Herein, we report the first two-dimensional chiral perovskite-like bismuth(III) iodide hybrid [(S)-3-aminopyrrolidinium I]2Bi2/3I4 (1) with a high phase transition temperature of 408.8 K, higher than most of the reported chiral lead-free hybrid semiconductors.

Comprehensively Optimizing Fenton Reaction Factors for Antitumor Chemodynamic Therapy by Charge-Reversal Theranostics.

Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(ß-amino esters) (PEG-PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG-PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG-PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.

The First Enantiomeric Stereogenic Sulfur-Chiral Organic Ferroelectric Crystals.

Chiral ferroelectric crystals with intriguing features have attracted great interest and many with point or axial chirality based on the stereocarbon have been successively developed in recent years. However, ferroelectric crystals with stereogenic heteroatomic chirality have never been documented so far. Here, we discover and report a pair of enantiomeric stereogenic sulfur-chiral single-component organic ferroelectric crystals, Rs -tert-butanesulfinamide (Rs -tBuSA) and Ss -tert-butanesulfinamide (Ss -tBuSA) through the deep understanding of the chemical design of molecular ferroelectric crystals. Both enantiomers adopt chiral-polar point group 2 (C2 ) and exhibit mirror-image relationships. They undergo high-temperature 432F2-type plastic ferroelectric phase transition around 348 K. The ferroelectricity has been well confirmed by ferroelectric hysteresis loops and domains. Polarized light microscopy records the evolution of the ferroelastic domains, according with the fact that the 432F2-type phase transition is both ferroelectric and ferroelastic. The very soft characteristics with low elastic modulus and hardness reveals their excellent mechanical flexibility. This finding indicates the first stereosulfur chiral molecular ferroelectric crystals, opening up new fertile ground for exploring molecular ferroelectric crystals with great application prospects.

Fluorination Enables Dual Ferroelectricity in Both Solid- and Liquid-Crystal Phases.

Ferroelectric materials are a special type of polar substances, including solids or liquid crystals. However, obtaining a material to be ferroelectric in both its solid crystal (SC) and liquid crystal (LC) phases is a great challenge. Moreover, although cholesteric LCs inherently possess the advantage of high fluidity, their ferroelectricity remains unknown. Here, through the reasonable H/F substitution on the fourth position of the phenyl group of the parent nonferroelectric dihydrocholesteryl benzoate, we designed ferroelectric dihydrocholesteryl 4-fluorobenzoate (4-F-BDC), which shows ferroelectricity in both SC and cholesteric LC phases. The fluorination induces a lower symmetric polar P1 space group and a new solid-to-solid phase transition in 4-F-BDC. Beneficial from fluorination, the SC and cholesteric LC phases of 4-F-BDC show clear ferroelectricity, as confirmed by well-shaped polarization-voltage hysteresis loops. The dual ferroelectricity in both SC and cholesteric LC phases of a single material was rarely found. This work offers a viable case for the exploration of the interplay between ferroelectric SC and LC phases and provides an efficient approach for designing ferroelectrics with dual ferroelectricity and cholesteric ferroelectric liquid crystals.

High-T c Single-Component Organosilicon Ferroelectric Crystal Obtained by H/F Substitution.

Organic single-component ferroelectrics are highly desirable for their low molecular mass, light weight, low processing temperature, and excellent film-forming properties. Organosilicon materials with a strong film-forming ability, weather resistance, nontoxicity, odorlessness, and physiological inertia are very suitable for device applications related to the human body. However, the discovery of high-T c organic single-component ferroelectrics has been very scarce, and the organosilicon ones even less so. Here, we used a chemical design strategy of H/F substitution to successfully synthesize a single-component organosilicon ferroelectric tetrakis(4-fluorophenylethynyl)silane (TFPES). Systematic characterizations and theory calculations revealed that, compared with the parent nonferroelectric tetrakis(phenylethynyl)silane, fluorination caused slight modifications of the lattice environment and intermolecular interactions, inducing a 4/mmmFmm2-type ferroelectric phase transition at a high T c of 475 K in TFPES. To our knowledge, this T c should be the highest among the reported organic single-component ferroelectrics, providing a wide operating temperature range for ferroelectrics. Moreover, fluorination also brought about a significant improvement in the piezoelectric performance. Combined with excellent film properties, the discovery of TFPES provides an efficient path for designing ferroelectrics suitable for biomedical and flexible electronic devices.

Terpyridine-Grafted Nitrogen-Terminal Endowing Cyanine with Metal-Ion-Regulated Photophysical Properties for Cancer Theranostics.

Heptamethine cyanines (Cy7) are one of the most important dyes in bioimaging and phototherapy, but they often suffer from poor photostability or limited photothermal conversion efficiency. Here, a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is demonstrated. By innovatively modifying the nitrogen with functional groups, a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold (denoted as CydtPy) was synthesized and exhibited tunable photophysical properties when chelating with various metal ions (Mn2+, Fe2+, etc.). In comparison with metal-ion-free PEGylated CydtPy (LET-11), Mn2+-chelated LET-11 (namely, LET-11-Mn) exhibited the increased fluorescence emission intensity, and Fe2+-chelated LET-11 (namely, LET-11-Fe) showed the enhanced photostability with ~2-fold increase in photothermal conversion efficiency. By simply switching the chelated metal ion species, LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging, magnetic resonance imaging, or photoacoustic imaging. Furthermore, LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in vivo. This work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.

A photoluminescent chiral lead-free hybrid ferroelastic semiconductor with switchable second-harmonic generation.

Chiral organic-inorganic hybrid semiconductors (COIHSs) dominated by lead halides have recently gained tremendous interest. Here, we report a lead-free photoluminescent COIHS [R-3-hydroxylpiperidinium]2SbCl5 with a bandgap of 3.14 eV. It shows a ferroelastic phase transition at 341 K accompanied by a switchable second-harmonic generation response and presents clear ferroelastic domains, which are rarely found in lead-free COIHSs.

Improving the activity and thermostability of PETase from Ideonella sakaiensis through modulating its post-translational glycan modification.

The large-scale preparation of Polyehylene terephthalate (PET) hydrolysing enzymes in low-cost is critical for the biodegradation of PET in industry. In the present study, we demonstrate that the post-translational glycosylation of Pichia pastoris makes it a remarkable host for the heterologous expression of PETase from Ideonella sakaiensis 201-F6 (IsPETase). Taking advantage of the abundant N- and O-linked glycosylation sites in IsPETase and the efficient post-translational modification in endoplasmic reticulum, IsPETase is heavily glycosylated during secretory expression with P. pastoris, which improves the specific activity and thermostability of the enzyme dramatically. Moreover, the specific activity of IsPETase increased further after the bulky N-linked polysaccharide chains were eliminated by Endo-ß-N-acetylglucosaminidase H (Endo H). Importantly, the partially deglycosylated IsPETase still maintained high thermostability because of the remaining mono- and oligo-saccharide residues on the protein molecules. Consequently, the partially deglycosylated IsPETase was able to be applied at 50 °C and depolymerized raw, untreated PET flakes completely in 2 to 3 days. This platform was also applied for the preparation of a famous variant of IsPETase, Fast-PETase, and the same result was achieved. Partially deglycosylated Fast-PETase demonstrates elevated efficiency in degrading postconsumer-PET trays under 55 °C than 50 °C, the reported optimal temperature of Fast-PETase. The present study provides a strategy to modulate thermostable IsPETase through glycosylation engineering and paves the way for promoting PET biodegradation from laboratories to factories.

Remarkable Enhancement of Piezoelectric Performance by Heavy Halogen Substitution in Hybrid Perovskite Ferroelectrics.

Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric (d33) and piezoelectric voltage (g33) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d33 and g33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me3NCH2Cl]CdBrCl2 to mitigate and roughly address this issue by heavy halogen substitution. The introduction of a large-size halide element softens the metal-halide bonds and reduces the polarization switching barrier, resulting in excellent piezoelectric response with a large d33 (∼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me3NCH2Cl]CdCl3 (You et al. Science2017, 357, 306-309). More strikingly, [Me3NCH2Cl]CdBrCl2 simultaneously shows a giant g33 of 6215 × 10-3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me3NCH2Cl]CdBrCl2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.

Genome sequence and comparative analysis of fungal antagonistic strain Bacillus velezensis LJBV19.

Bacillus species as fungal antagonistic agents have been widely used in the agriculture and considered as safe products for the management of plant pathogens. In this study, we reported the whole genome sequence of strain LJBV19 isolated from grapevine rhizosphere soil. Strain LJBV19 was identified as Bacillus velezensis through morphological, physicochemical, molecular analysis and genome comparison. Bacillus velezensis LJBV19 had a significant inhibitory effect on the growth of Magnaporthe oryzae with an inhibition ratio up to 75.55% and showed broad spectrum of activity against fungal phytopathogens. The 3,973,013-bp circular chromosome with an average GC content of 46.5% consisted of 3993 open reading frames (ORFs), and 3308 ORFs were classified into 19 cluster of orthologous groups of proteins (COG) categories. Genes related to cell wall degrading enzymes were predicted by Carbohydrate-Active enZYmes (CAZy) database and validated at the metabolic level, producing 0.53 ± 0.00 U/mL cellulose, 0.14 ± 0.01 U/mL chitinase, and 0.11 ± 0.01 U/mL chitosanase. Genome comparison confirmed the taxonomic position of LJBV19, conserved genomic structure, and genetic homogeneity. Moreover, 13 gene clusters for biosynthesis of secondary metabolites in LJBV19 genome were identified and two unique clusters (clusters 2 and 12) shown to direct an unknown compound were only present in strain LJBV19. In general, our results will provide insights into the antifungal mechanisms of Bacillus velezensis LJBV19 and further application of the strain.

Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells / 中华肿瘤杂志

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

A 1-µm-Band Injection-Locked Semiconductor Laser with a High Side-Mode Suppression Ratio and Narrow Linewidth.

We demonstrate a narrow-linewidth, high side-mode suppression ratio (SMSR) semiconductor laser based on the external optical feedback injection locking technology of a femtosecond-apodized (Fs-apodized) fiber Bragg grating (FBG). A single frequency output is achieved by coupling and integrating a wide-gain quantum dot (QD) gain chip with a Fs-apodized FBG in a 1-µm band. We propose this low-cost and high-integration scheme for the preparation of a series of single-frequency seed sources in this wavelength range by characterizing the performance of 1030 nm and 1080 nm lasers. The lasers have a maximum SMSR of 66.3 dB and maximum output power of 134.6 mW. Additionally, the lasers have minimum Lorentzian linewidths that are measured to be 260.5 kHz; however, a minimum integral linewidth less than 180.4 kHz is observed by testing and analyzing the power spectra of the frequency noise values of the lasers.

ILP-2: A New Bane and Therapeutic Target for Human Cancers.

Inhibitor of apoptosis protein-related-like protein-2 (ILP-2), also known as BIRC-8, is a member of the inhibitor of apoptosis protein (IAPs) family, which mainly encodes the negative regulator of apoptosis. It is selectively overexpressed in a variety of human tumors and can help tumor cells evade apoptosis, promote tumor cell growth, increase tumor cell aggressiveness, and appears to be involved in tumor cell resistance to chemotherapeutic drugs. Several studies have shown that downregulation of ILP-2 expression increases apoptosis, inhibits metastasis, reduces cell growth potential, and sensitizes tumor cells to chemotherapeutic drugs. In addition, ILP-2 inhibits apoptosis in a unique manner; it does not directly inhibit the activity of caspases but induces apoptosis by cooperating with other apoptosis-related proteins. Here, we review the current understanding of the various roles of ILP-2 in the apoptotic cascade and explore the use of interfering ILP-2, and the combination of related anti-tumor agents, as a novel strategy for cancer therapy.

CircFAT1 Promotes Lung Adenocarcinoma Progression by Sequestering miR-7 from Repressing IRS2-ERK-mediated CCND1 Expression.

Our understanding of coding gene functions in lung cancer leads to the development of multiple generations of targeted drugs. Noncoding RNAs, including circular RNAs (circRNAs), have been demonstrated to play a vital role in tumorigenesis. Uncovering the functions of circRNAs in tumorigenesis and their underlying regulatory mechanisms may shed new light on the development of novel diagnostic and therapeutic strategies for human cancer. Here we report the important role of circFAT1 in lung adenocarcinoma (LUAD) progression and the potential impact of circFAT1 on LUAD treatment. We found that circFAT1 was one of the top expressed circRNAs in A549 cells by circRNA-seq and was significantly upregulated in human LUAD tissues. Multiple cellular assays with A549 and PC9 LAUD cell lines under both gain-of-function and loss-of-function conditions demonstrated that circFAT1 promoted proliferation of LUAD cells in vitro and in vivo. At molecular level, circFAT1 sequestered miR-7 to upregulate IRS2, which in turn regulated downstream ERK1/2 phosphorylation and CCND1 expression, ultimately promoting tumor progression. In addition, we showed that DDP treatment was much more effective in circFAT1 knockdown tumor cells in vitro and in a xenograft tumor model. Our results indicate that circFAT1 promote tumorigenesis in LUAD through sequestering miR-7, consequently upregulating IRS2-ERK1/2-mediated CCND1 expression, and can be a valuable therapeutic target and an important parameter for precision treatment in LUAD patients.

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.

An unprecedented azobenzene-based organic single-component ferroelectric.

Organic single-component ferroelectrics, as an important class of metal-free ferroelectrics, are highly desirable because of their easy processing, mechanical flexibility, and biocompatibility. However, although nearly 50 years have passed since the discovery of photochromism in azobenzene-doped cholesteric liquid crystals, ferroelectricity has never been found in azobenzene-based crystals. Here, we use an amino group to substitute a fluorine atom of 2,2',4,4',6,6'-hexafluoroazobenzene, which successfully introduces ferroelectricity into 2-amino-2',4,4',6,6'-pentafluoroazobenzene (APFA). APFA shows an extremely high Curie temperature (T c) of 443 K, which is outstanding among single-component ferroelectrics. It also exhibits an indirect optical band gap of 2.27 eV as well as photoisomerization behavior between the trans-form and the cis-form triggered by pedal motion. To our knowledge, APFA is the first azobenzene-based ferroelectric crystal. This work opens an avenue to design excellent single-component ferroelectrics and will inspire the exploration of azobenzene-based ferroelectrics for promising applications in biofriendly ferroelectric devices.

Bioactive cytomembrane@poly(citrate-peptide)-miRNA365 nanoplatform with immune escape and homologous targeting for colon cancer therapy.

Colon cancer is one of the most common gastrointestinal tumors in the world. Currently, the commonly used methods such as radiotherapy, chemotherapy and drug treatments are often ineffective and have significant side effects. Here we developed a safe and efficient biomaterials based anti-tumor nanoplatform (M@NPs/miR365), which was formed with poly (citrate-peptide) (PCP), miRNA365 mimic and MC38 cancer cell membrane (M). PCP could efficiently deliver miR365 mimic into MC38 cancer cells, promote the apoptosis of MC38 tumor cells and regulate the expression of Bcl2 and Ki67 in vitro. Tumor cell membranes were prepared by a fast and convenient sonication method. This tumor cell membrane-coated drug delivery system M@NPs can effectively reduce macrophage uptake and increase the stability of NPs. And the MC38 tumor model mice experiment showed that M@NPs/miR365 via caudal vein injection effectively inhibit tumor development. Based on the immune escape and homologous targeting of cancer cells and efficient gene transfection ability of NPs, this "Trojan horse" like "Pseudotumor cell" carries the target gene miR365 mimic to the tumor site and realizes cancer therapy. Noteworthy, the drug delivery system has good biocompatibility. Thus, this safe drug delivery strategy mediated by cancer cell membrane and gene therapy may have a certain significance for reducing the gap between nanoplatform and tumor clinical treatment.