In Situ Construction of NiCoMn-LDH Derived from Zeolitic Imidazolate Framework on Eggshell-Like Carbon Skeleton for High-Performance Flexible Supercapacitors.

Active compounds based on LDH (ternary layered double hydroxide) are considered the perfect supercapacitor electrode materials on account of their superior electrochemical qualities and distinct structural characteristics, and flexible supercapacitors are an ideal option as an energy source for wearable electronics. However, the prevalent aggregation effect of LDH materials results in significantly compromised actual specific capacitance, which limits its broad practical applications. In this research, a 3D eggshell-like interconnected porous carbon (IPC) framework with confinement and isolation capability is designed and synthesized by using glucose as the carbon source to disperse the LDH active material and enhance the conductivity of the composite material. Second, by constructing NiCoMn-LDH nanocage structure based on ZIF-67 (zeolitic imidazolate framework-67) at the nanometer scale the obtained IPC/NiCoMn-LDH electrode material can expose more active sites, which allows to achieve excellent specific capacitance (2236 F g-1/ 310.6 mAh g-1 at 1 A g-1), good rate as well as the desired cycle stability (85.9% of the initial capacitance upon 5000 cycles test). The constructed IPC/NiCoMn-LDH//IPC ASC (asymmetric supercapacitor) exhibits superior capacitive property (135 F g-1/60.1 mAh g-1 at 0.5 A g-1) as well as desired energy density (40 Wh kg-1 at 800 W kg-1).

Exploration and validation of a combined Hypoxia and m6A/m5C/m1A regulated gene signature for prognosis prediction of liver cancer.

BACKGROUND: It is widely acknowledged that hypoxia and m6A/m5C/m1A RNA modifications promote the occurrence and development of tumors by regulating the tumor microenvironment. This study aimed to establish a novel liver cancer risk signature based on hypoxia and m6A/m5C/m1A modifications. METHODS: We collected data from The Cancer Genome Atlas (TCGA-LIHC), the National Omics Data Encyclopedia (NODE-HCC), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) databases for our study (GSE59729, GSE41666). Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications. We stratified patients into high- and low-risk groups and assessed differences between these groups in terms of gene mutations, copy number variations, pathway enrichment, stemness scores, immune infiltration, and predictive capabilities of the model for immunotherapy and chemotherapy efficacy. RESULTS: Our analysis revealed a significantly correlated between hypoxia and methylation as well as m6A/m5C/m1A RNA methylation. The three-gene prognosis signature (CEP55, DPH2, SMS) combining hypoxia and m6A/m5C/m1A regulated genes exhibited strong predictive performance in TCGA-LIHC, NODE-HCC, and ICGC-LIHC-JP cohorts. The low-risk group demonstrated a significantly better overall survival compared to the high-risk group (p < 0.0001 in TCGA, p = 0.0043 in NODE, p = 0.0015 in ICGC). The area under the curve (AUC) values for survival at 1, 2, and 3 years are all greater than 0.65 in the three cohorts. Univariate and Multivariate Cox regression analyses of the three datasets indicated that the signature could serve as an independent prognostic predictor (p < 0.001 in the three cohorts). The high-risk group exhibited more genome changes and higher homologous recombination deficiency scores and stemness scores. Analysis of immune infiltration and immune activation confirmed that the signature was associated with various immune microenvironment characteristics. Finally, patients in the high-risk group experienced a more favorable response to immunotherapy, and various common chemotherapy drugs. CONCLUSION: Our prognostic signature which integrates hypoxia and m6A/m5C/m1A-regulated genes, provides valuable insights for clinical prediction and treatment guidance for liver cancer patients.

Receptor discordance among primary tumors, brain metastases and extra-brain metastases in patients with breast cancer.

Background: To investigate the expression status of estrogen receptor (ER), progesterone receptor (PR) and HER2 in patients with breast cancer brain metastases (BM). Methods: Patients who underwent craniotomy for BM were included. The status of ER, PR and HER2 (including HER2-low expression) in primary breast tumors (PT), BM and extra-BM (EM) was determined. Results: Between PT and BM, conversion of hormone receptor and HER2 occurred in 28% (30/107) and 12% (10/86) of cases. When considering three-tiered categorization of HER2, the conversion rate reached 31%. In the paired EM and BM (n = 39), the discordance rates were 18%, 3% and 22%, respectively. Conclusion: Receptor discordance was dynamic and relevant, especially using new HER2 categorization.

Novel prognostic gene signature for pancreatic ductal adenocarcinoma based on hypoxia.

BACKGROUND: Currently, there is lack of marker to accurately assess the prognosis of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). This study aims to establish a hypoxia-related risk scoring model that can effectively predict the prognosis and chemotherapy outcomes of PDAC patients. METHODS: Using unsupervised consensus clustering algorithms, we comprehensively analyzed The Cancer Genome Atlas (TCGA) data to identify two distinct hypoxia clusters and used the weighted gene co-expression network analysis (WGCNA) to examine gene sets significantly associated with these hypoxia clusters. Then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used to construct a signature and its efficacy was evaluated using the International Cancer Genome Consortium (ICGC) PDAC cohort. Further, the correlation between the risk scores obtained from the signature and carious clinical, pathological, immunophenotype, and immunoinfiltration factors as well as the differences in immunotherapy potential and response to common chemotherapy drugs between high-risk and low-risk groups were evaluated. RESULTS: From a total of 8 significantly related modules and 4423 genes, 5 hypoxia-related signature genes were identified to construct a risk model. Further analysis revealed that the overall survival rate (OS) of patients in the low-risk group was significantly higher than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk scoring signature was an independent factor for prognosis prediction. Analysis of immunocyte infiltration and immunophenotype showed that the immune score and the anticancer immune response in the high-risk were significantly lower than that in the low-risk group. CONCLUSION: The constructed hypoxia-associated prognostic signature demonstrated could be used as a potential risk classifier for PDAC.

Genome-wide identification and expression analysis of the BURP domain-containing genes in Gossypium hirsutum.

BACKGROUND: Many BURP domain-containing proteins, which are unique to plants, have been identified. They performed diverse functions in plant development and the stress response. To date, only a few BURP domain-containing genes have been studied, and no comprehensive analysis of the gene family in cotton has been reported. RESULTS: In this study, 18, 17 and 30 putative BURP genes were identified in G. raimondii (D5), G. arboreum (A2) and G. hirsutum (AD1), respectively. These BURP genes were phylogenetically classified into eight subfamilies, which were confirmed by analyses of gene structures, motifs and protein domains. The uneven distribution of BURPs in chromosomes and gene duplication analysis indicated that segmental duplication might be the main driving force of the GhBURP family expansion. Promoter regions of all GhBURPs contained at least one putative stress-related cis-elements. Analysis of transcriptomic data and qRT-PCR showed that GhBURPs showed different expression patterns in different organs, and all of them, especially the members of the RD22-like subfamily, could be induced by different stresses, such as abscisic acid (ABA) and salicylic acid (SA), which indicated that the GhBURPs may performed important functions in cotton's responses to various abiotic stresses. CONCLUSIONS: Our study comprehensively analyzed BURP genes in G. hirsutum, providing insight into the functions of GhBURPs in cotton development and adaptation to stresses.

Transcriptome analysis reveals differences in the mechanisms of fiber initiation and elongation between long- and short-fiber cotton (Gossypium hirsutum L.) lines.

BACKGROUND: Improving the yield and fiber quality of upland cotton is a goal of plant breeders. However, increasing the yield and quality of cotton fibers is becoming more urgent. While the growing human population needs more cotton fiber, climate change is reducing the amount of land on which cotton can be planted, or making it difficult to ensure that water and other resources will be available in optimal quantities. The most logical means of improving yield and quality is understanding and manipulating the genes involved. Here, we used comparative transcriptomics to explore differences in gene expression between long- and short-fiber cotton lines to identify candidate genes useful for cotton improvement. RESULTS: Light and electron microscopy revealed that the initial fiber density was significantly greater in our short-fiber group (SFG) than in our long-fiber group (LFG). Compared with the SFG fibers, the LFG fibers were longer at all developmental stages. Comparison of the LFG and SFG transcriptomes revealed a total of 3538 differentially expressed genes (DEGs). Notably, at all three developmental stages examined, two expression patterns, consistently downregulated (profile 0) and consistently upregulated (profile 7), were identified, and both were significantly enriched in the SFG and LFG. Twenty-two DEGs known to be involved in fiber initiation were detected in profile 0, while 31 DEGs involved in fiber elongation were detected in profile 7. Functional annotation suggested that these DEGs, which included ERF1, TUA2, TUB1, and PER64, affect fiber elongation by participating in the ethylene response, microtubule synthesis, and/or the peroxidase (POD) catalytic pathway. qRT-PCR was used to confirm the RNA sequencing results for select genes. CONCLUSIONS: A comparison of SFG and LFG transcription profiles revealed modest but important differences in gene expression between the groups. Notably, our results confirm those of previous studies suggesting that genes involved in ethylene, tubulin, and POD pathways play important roles in fiber development. The 22 consistently downregulated DEGs involved in fiber initiation and the 31 consistently upregulated genes involved in fiber elongation are seemingly good candidate genes for improving fiber initiation and elongation in cotton.

Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly.

BACKGROUND: The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance. METHODS: We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer. RESULTS: The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1-dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H2O2) in prostate cancer cells. CONCLUSIONS: SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.

Genome-wide identification and characterization of TALE superfamily genes in cotton reveals their functions in regulating secondary cell wall biosynthesis.

BACKGROUND: Cotton fiber length and strength are both key traits of fiber quality, and fiber strength (FS) is tightly correlated with secondary cell wall (SCW) biosynthesis. The three-amino-acid-loop-extension (TALE) superclass homeoproteins are involved in regulating diverse biological processes in plants, and some TALE members has been identified to play a key role in regulating SCW formation. However, little is known about the functions of TALE members in cotton (Gossypium spp.). RESULTS: In the present study, based on gene homology, 46, 47, 88 and 94 TALE superfamily genes were identified in G. arboreum, G. raimondii, G. barbadense and G. hirsutum, respectively. Phylogenetic and evolutionary analysis showed the evolutionary conservation of two cotton TALE families (including BEL1-like and KNOX families). Gene structure analysis also indicated the conservation of GhTALE members under selection. The analysis of promoter cis-elements and expression patterns suggested potential transcriptional regulation functions in fiber SCW biosynthesis and responses to some phytohormones for GhTALE proteins. Genome-wide analysis of colocalization of TALE transcription factors with SCW-related QTLs revealed that some BEL1-like genes and KNAT7 homologs may participate in the regulation of cotton fiber strength formation. Overexpression of GhKNAT7-A03 and GhBLH6-A13 significantly inhibited the synthesis of lignocellulose in interfascicular fibers of Arabidopsis. Yeast two-hybrid (Y2H) experiments showed extensive heteromeric interactions between GhKNAT7 homologs and some GhBEL1-like proteins. Yeast one-hybrid (Y1H) experiments identified the upstream GhMYB46 binding sites in the promoter region of GhTALE members and defined the downstream genes that can be directly bound and regulated by GhTALE heterodimers. CONCLUSION: We comprehensively identified TALE superfamily genes in cotton. Some GhTALE members are predominantly expressed during the cotton fiber SCW thicking stage, and may genetically correlated with the formation of FS. Class II KNOX member GhKNAT7 can interact with some GhBEL1-like members to form the heterodimers to regulate the downstream targets, and this regulatory relationship is partially conserved with Arabidopsis. In summary, this study provides important clues for further elucidating the functions of TALE genes in regulating cotton growth and development, especially in the fiber SCW biosynthesis network, and it also contributes genetic resources to the improvement of cotton fiber quality.

Genome-wide identification and expression analyses of the pectate lyase (PEL) gene family in cotton (Gossypium hirsutum L.).

BACKGROUND: Pectin is a major component and structural polysaccharide of the primary cell walls and middle lamella of higher plants. Pectate lyase (PEL, EC 4.2.2.2), a cell wall modification enzyme, degrades de-esterified pectin for cell wall loosening, remodeling and rearrangement. Nevertheless, there have been few studies on PEL genes and no comprehensive analysis of the PEL gene family in cotton. RESULTS: We identified 53, 42 and 83 putative PEL genes in Gossypium raimondii (D5), Gossypium arboreum (A2), and Gossypium hirsutum (AD1), respectively. These PEL genes were classified into five subfamilies (I-V). Members from the same subfamilies showed relatively conserved gene structures, motifs and protein domains. An analysis of gene chromosomal locations and gene duplication revealed that segmental duplication likely contributed to the expansion of the GhPELs. The 2000 bp upstream sequences of all the GhPELs contained auxin response elements. A transcriptomic data analysis showed that 62 GhPELs were expressed in various tissues. Notably, most (29/32) GhPELs of subfamily IV were preferentially expressed in the stamen, and five GhPELs of subfamily V were prominently expressed at the fiber elongation stage. In addition, qRT-PCR analysis revealed the expression characteristics of 24 GhPELs in four pollen developmental stages and significantly different expression of some GhPELs between long- and short-fiber cultivars. Moreover, some members were responsive to IAA treatment. The results indicate that GhPELs play significant and functionally diverse roles in the development of different tissues. CONCLUSIONS: In this study, we comprehensively analyzed PELs in G. hirsutum, providing a foundation to better understand the functions of GhPELs in different tissues and pathways, especially in pollen, fiber and the auxin signaling pathway.

Proteomic Analysis of Differences in Fiber Development between Wild and Cultivated Gossypium hirsutum L.

Upland cotton (Gossypium hirsutum L.) is one of the world's most important fiber crops, accounting for more than 90% of all cotton production. While their wild progenitors have relatively short and coarse, often tan-colored fibers, modern cotton cultivars possess longer, finer, stronger, and whiter fiber. In this study, the wild and cultivated cottons (YU-3 and TM-1) selected show significant differences on fibers at 10 days postanthesis (DPA), 20 DPA, and mature stages at the morphological level. To explore the effects of domestication, reveal molecular mechanisms underlying these phenotypic differences, and better inform our efforts to further enhance cotton fiber quality, isobaric tags for relative and absolute protein quantification-facilitated proteomic methods were performed on developing fibers. There were 6990 proteins identified; among them, 336 were defined as differentially expressed proteins between fibers of wild versus domesticated cotton. The down- or up-regulated proteins in wild cotton were involved in phenylpropanoid biosynthesis, zeatin biosynthesis, fatty acid elongation, and other processes. Association analysis between transcriptome and proteome showed positive correlations between transcripts and proteins at both 10 DPA and 20 DPA. Differences in proteomics have been verified at the mRNA level by quantitative real-time polymerase chain reaction and have been validated at the physiological and biochemical levels by POD (peroxidase) activity assays and ZA (zeatin) content estimates. This work corroborates the major pathways involved in cotton fiber development and demonstrates that POD activity and zeatin content have a great potential related to fiber elongation and thickening.

mTORC1/S6K1 signaling promotes sustained oncogenic translation through modulating CRL3IBTK-mediated ubiquitination of eIF4A1 in cancer cells.

Enhanced protein synthesis is a crucial molecular mechanism that allows cancer cells to survive, proliferate, metastasize, and develop resistance to anti-cancer treatments, and often arises as a consequence of increased signaling flux channeled to mRNA-bearing eukaryotic initiation factor 4F (eIF4F). However, the post-translational regulation of eIF4A1, an ATP-dependent RNA helicase and subunit of the eIF4F complex, is still poorly understood. Here, we demonstrate that IBTK, a substrate-binding adaptor of the Cullin 3-RING ubiquitin ligase (CRL3) complex, interacts with eIF4A1. The non-degradative ubiquitination of eIF4A1 catalyzed by the CRL3IBTK complex promotes cap-dependent translational initiation, nascent protein synthesis, oncogene expression, and cervical tumor cell growth both in vivo and in vitro. Moreover, we show that mTORC1 and S6K1, two key regulators of protein synthesis, directly phosphorylate IBTK to augment eIF4A1 ubiquitination and sustained oncogenic translation. This link between the CRL3IBTK complex and the mTORC1/S6K1 signaling pathway, which is frequently dysregulated in cancer, represents a promising target for anti-cancer therapies.

A Novel Pancreatic Cancer Hypoxia Status Related Gene Signature for Prognosis and Therapeutic Responses.

Pancreatic cancer (PAC) is a highly fatal and aggressive type of cancer. Hypoxia is a common feature of PAC. The aim of this study was to develop a hypoxia status-related prognostic model for predicting the survival outcomes in PAC. The data sets of PAC from The Cancer Genome Atlas and the International Cancer Genome Consortium were used to construct and validate the signature. A 6 hypoxia status-related differential expression genes prognostic model for predicting the survival outcomes was established. The Kaplan-Meier analysis and Received operating characteristic curve indicated the good performance of the signature at predicting overall survival. Univariate and Multivariate Cox regression revealed that the signature was an independent prognostic factor in PAC. Weighted Gene Co-expression Network Analysis and immune infiltration analysis indicated that Immune-related pathways and immune cell infiltration was mostly enriched in the low-risk group, which presented a better prognosis. We also evaluated the predictive of the signature for immunotherapy and chemoradiotherapy. Risk gene LY6D may be a potential prognostic predictor of PAC. This model can be used as an independent prognostic factor for predicting clinical outcomes and a possible classifier for response to chemotherapy.

Promoting Effect of Common Marine Cations on Hydrate Dissociation and Structural Evolution under a Static Electric Field.

Natural gas hydrate, a potential energy resource, is attracting worldwide attention. In this study, we propose a new method of hydrate dissociation which uses seawater and electrostatic fields (SE method) cooperatively. The hydrate molecular dissociation mechanism of gas hydrate is a key issue in studying the kinetic properties of gas hydrate using the SE method. Therefore, molecular dynamics simulations were used to investigate the thermodynamic properties and structural changes of methane hydrate (MH) in multiple kinds of salt solutions under an electrostatic field. The results show that the electric field can drive cations into the MH phase to form a series of random semiopen cages, which are essentially temporary and metastable. The variation in free energy indicates that it is more difficult for divalent cations to enter the hydrate phase than monovalent cations, meaning that the hydrate structures formed with divalent cations are more unstable. Then, the ion current occurred in the hydrate phase (called ion migration in this study), which greatly accelerated hydrate dissociation. In contrast, the promotion effect of cations with the same charge on MH dissociation is as follows: Sr2+ > K+ ≈ Na+ > Ca2+ ≈ Mg2+. In general, the presence of common marine cations enhanced the promotion effect of the electric field on gas hydrate dissociation.

Disruption of the Keap1-mTORC2 axis by cancer-derived Keap1/mLST8 mutations leads to oncogenic mTORC2-AKT activation.

The mechanistic target of the rapamycin (mTOR) pathway, which participates in the regulation of cellular growth and metabolism, is aberrantly regulated in various cancer types. The mTOR complex 2 (mTORC2), which consists of the core components mTOR, Rictor, mSin1, and mLST8, primarily responds to growth signals. However, the coordination between mTORC2 assembly and activity remains poorly understood. Keap1, a major sensor of oxidative stress in cells, functions as a substrate adaptor for Cullin 3-RING E3 ubiquitin ligase (CRL3) to promote proteasomal degradation of NF-E2-related factor 2 (NRF2), which is a transcription factor that protects cells against oxidative and electrophilic stress. In the present study, we demonstrate that Keap1 binds to mLST8 via a conserved ETGE motif. The CRL3Keap1 ubiquitin ligase complex promotes non-degradative ubiquitination of mLST8, thus reducing mTORC2 complex integrity and mTORC2-AKT activation. However, this effect can be prevented by oxidative/electrophilic stresses and growth factor signaling-induced reactive oxygen species (ROS) burst. Cancer-derived Keap1 or mLST8 mutations disrupt the Keap1-mLST8 interaction and allow mLST8 to evade Keap1-mediated ubiquitination, thereby enhancing mTORC2-AKT activation and promoting cell malignancy and remodeling cell metabolism. Our findings provide new insights into the molecular mechanisms of Keap1/mLST8 mutation-driven tumorigenesis by promoting mTORC2-AKT activation, which is independent of the canonical NRF2 pathway.

Multimedia Mixed Reality Interactive Shared Decision-Making Game in Children with Moderate to Severe Atopic Dermatitis, a Pilot Study.

(1) Objective: Atopic dermatitis (AD) is a recurring skin disease that affects children's daily activities and sleep quality. Due to the limitations of children's understanding and ability to express themselves, shared decision making (SDM) is often made by guardians, which thus affects the acceptance and effectiveness of children's treatments. Previous studies have demonstrated that involving both children and parents in decision making may help improve treatment outcomes; thus, we designed a multimedia mixed reality (MR) interactive game of SDM for children with moderate to severe AD. (2) Methods: Research participants included 6-18-year-old patients with moderate to severe AD. This research consisted of the following steps: designing SDM; character setting and visual design; performing games; system modification and optimization; screen editing and dubbing; and user testing and questionnaires by the System Usability Scale (SUS). (3) Results: We completed the SDM design for children with moderate to severe AD. Four different treatments were biologics, oral immune-modulating drugs, phototherapy, and wet wrap. An animated PowerPoint slide showed the AD apple rolling around before treatments and the AD apple sleeping soundly after treatments. Instructions with video teaching for the four different treatments were played, and then, the MR was turned on so that the patients could help the AD apple in the metaverse to undergo these four treatments. A total of 12 moderate to severe AD patients and six control patients used the game, all aged between six and eighteen years old, with an average SUS score of 81.0 and a standard error of 2.1 points. Adjective ratings yielded a rating between good and excellent. The game showed acceptable usability. We found no statistically significant differences in SUS scores between patients with and without moderate to severe AD or between boys and girls nor significant associations between SUS and age or severity. The analysis identified that the two items with the lowest SUS scores were "I think that I would need the support of a technical person to be able to use this product" and "I needed to learn a lot of things before I could get going with this product". Both of these comments show the limitations of this game. (4) Conclusions: Overall, this study provides the first MR SDM game that has passed the SUS and can be used as an aid in clinical SDM.

Mechanism of miR-340-5p in laryngeal cancer cell proliferation and invasion through the lncRNA NEAT1/MMP11 axis.

OBJECTIVES: Laryngeal cancer (LC), with a relatively rare diagnosis, is a primary malignancy originating from laryngeal mucosa. This study investigated the mechanisms of microRNA (miR)- 340-5p in LC cell proliferation and invasion. METHODS: The expression patterns of miR-340-5p, long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1), and matrix metallopeptidase 11 (MMP11) in LC cells, tissues, and para-carcinoma tissues, and human bronchial epithelial cells (HBEC) were examined via RT-qPCR. The effects of elevating or silencing miR-340-5p on LC cell proliferation and invasion were examined. The subcellular localization of lncRNA NEAT1 was determined. The binding relations among miR-340-5p, lncRNA NEAT1, and MMP11 were verified. Functional rescue experiments were designed to verify the functions of lncRNA NEAT1 and MMP11 on LC cell proliferation and invasion. Nude-mouse tumor models were established to assess the role of miR-340-5p in LC in vivo. RESULTS: miR-340-5p was under-expressed in LC, and miR-340-5p overexpression repressed LC cell proliferation and invasion. Mechanically, miR-340-5p decreased lncRNA NEAT1 stability via directly binding to lncRNA NEAT1 and thus declined lncRNA NEAT1 expression in LC cells, while lncRNA NEAT1 accelerated MMP11 transcription via binding to heat shock factor 1 (HSF1). Overexpression of lncRNA NEAT1 or MMP11 reversed the repression of miR-340-5p overexpression on LC cell proliferation and invasion. In vivo, miR-340-5p overexpression repressed the tumor growth. CONCLUSION: miR-340-5p overexpression reduced lncRNA NEAT1 stability via binding to lncRNA NEAT1, which declined lncRNA NEAT1 expression and reduced the binding of lncRNA NEAT1 to HSF1 to further inhibit MMP11 transcription, thus repressing LC cell proliferation and invasion.

Genome-wide identification and expression analysis of fibrillin (FBN) gene family in tomato (Solanum lycopersicum L.).

Background: Fibrillin (FBN) proteins are widely distributed in the photosynthetic organs. The members of FBN gene family play important roles in plant growth and development, and response to hormone and stresses. Tomato is a vegetable crop with significantly economic value and model plant commonly used in research. However, the FBN family has not been systematical studied in tomato. Methods: In this study, 14 FBN genes were identified in tomato genome by Pfam and Hmmer 3.0 software. ExPASy, MEGA 6.0, MEME, GSDS, TBtools, PlantCARE and so on were used for physical and chemical properties analysis, phylogenetic analysis, gene structure and conserved motifs analysis, collinearity analysis and cis-acting element analysis of FBN family genes in tomato. Expression characteristics of SlFBNs in different tissues, fruit shape near isogenic lines (NILs), Pst DC3000 and ABA treatments were analyzed based on transcriptome data and quantitative Real-time qPCR (qRT-PCR) analysis. Results: The SlFBN family was divided into 11 subgroups. There were 8 FBN homologous gene pairs between tomato and Arabidopsis. All the members of SlFBN family contained PAP conserved domain, but their gene structure and conserved motifs showed apparent differences. The cis-acting elements of light and hormone (especially ethylene, methyl jasmonate (MeJA) and abscisic acid (ABA)) were widely distributed in the SlFBN promoter regions. The expression analysis found that most of SlFBNs were predominantly expressed in leaves of Heinz and S. pimpinellifolium LA1589, and showed higher expressions in mature or senescent leaves than in young leaves. Expression analysis of different tissues and fruit shape NILs indicated SlFBN1, SlFBN2b and SlFBN7a might play important roles during tomato fruit differentiation. All of the SlFBNs responded to Pst DC3000 and ABA treatments. The results of this study contribute to exploring the functions and molecular mechanisms of SlFBNs in leaf development, fruit differentiation, stress and hormone responses.

Effect Evaluation and Action Mechanism Analysis of "Profile Control + Plugging Removal" after Chemical Flooding.

The existing plugging removal operation in JZ9-3 oilfield has the disadvantages of small amount of plugging remover, fast injection speed, and short construction time. Under the condition of injection well suction profile reversal, plugging remover is difficult to enter the low permeability part and play the role of deep plugging removal. In order to improve the plugging removal effect, this paper used the physical simulation method to carry out the experimental study and mechanism analysis on the effect of water flooding, chemical flooding, and plugging removal measures of the multi-layer system combination model. The results showed that the recovery of general plugging removal after chemical flooding increases by only 0.70%, while the recovery of 'profile control + plugging removal' increases by '9.34% + 2.59%', and the amount of produced liquid decreases by more than 40%. It can be seen that the combined operation of profile control and plugging removal has dual effects of plugging and dredging and synergistic effect, which not only expands the swept volume, but also reduces the inefficient and ineffective cycles. On this basis, the optimization design and effect prediction of the target well W4-2 plugging removal scheme were carried out by using the numerical simulation method. Recommended scheme: inorganic gel profile control agent volume 13,243.6 m3, produced by the main agent (Na2O·nSiO2), isolation fluid (Water), and auxiliary agent (CaCl2) through multiple rounds of alternating injection into the reservoir. The plug removal agent (K2S2O8) injection volume is 100 m3, the concentration is 0.8%. The post-implementation 'Output/Input' ratio is expected to be 3.7.

4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway.

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.