RUNX1 promotes proliferation and migration in non-small cell lung cancer cell lines via the mTOR pathway.

RUNX1, a member of the RUNX family of metazoan transcription factors, participates in the regulation of differentiation, proliferation, and other processes involved in growth and development. It also functions in the occurrence and development of tumors. However, the role and mechanism of action of RUNX1 in non-small cell lung cancer (NSCLC) are not yet clear. We used a bioinformatics approach as well as in vitro and in vivo assays to evaluate the role of RUNX1 in NSCLC as the molecular mechanisms underlying its effects. Using the TCGA, GEO, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier databases, we screened the differentially expressed genes (DEGs) and found that RUNX1 was highly expressed in lung cancer and was associated with a poor prognosis. Immunohistochemical staining based on tissue chips from 110 samples showed that the expression of RUNX1 in lung cancer tissues was higher than that in adjacent normal tissues and was positively correlated with lymph node metastasis and TNM staging. In vitro experiments, we found that RUNX1 overexpression promoted cell proliferation and migration functions and affected downstream functional proteins by regulating the activity of the mTOR pathway, as confirmed by an analysis using the mTOR pathway inhibitor rapamycin. In addition, RUNX1 affected PD-L1 expression via the mTOR pathway. These results indicate that RUNX1 is a potential therapeutic target for NSCLC.

Phillyrin restores metabolic disorders in mice fed with high-fat diet through inhibition of interleukin-6-mediated basal lipolysis.

The function of white adipose tissue as an energy reservoir is impaired in obesity, leading to lipid spillover and ectopic lipid deposition. Adipose tissue inflammation can reduce the efficacy of lipid storage in adipocytes by augmenting basal lipolysis through producing interleukin-6 (IL-6). Therefore, pharmacological compounds targeting adipose tissue inflammation or IL-6 signaling might have the potential to combat obesity. This study aims to investigate the impact of Phillyrin, which is frequently used for treating respiratory infections in clinics in China, on obesity-related metabolic dysfunctions. Firstly, a mouse model of diet-induced obesity is used to assess the pharmacological applications of Phillyrin on obesity in vivo. Secondly, ex vivo culture of adipose tissue explants is utilized to investigate actions of Phillyrin on IL-6-linked basal lipolysis. Thirdly, a mouse model of IL-6 injection into visceral adipose tissue is explored to confirm the anti-basal lipolytic effect of Phillyrin against IL-6 in vivo. The results show that Phillyrin treatment reduces circulating level of glycerol, decreases hepatic steatosis and improves insulin sensitivity in obese mice. Meanwhile, Phillyrin attenuates obesity-related inflammation and IL-6 production in adipose tissue in obese mice. Furthermore, Phillyrin treatment results in resistance to IL-6-induced basal lipolysis in adipose tissue through suppressing expression of adipose triglyceride lipase (ATGL) both in vivo and in vitro. Collectively, these findings suggest that Phillyrin can restrain lipid efflux from inflamed adipose tissue in obesity by inhibiting IL-6-initiated basal lipolysis and ATGL expression, and thus is a potential candidate in the treatment of obesity-associated complications.

Gene-environment interaction between circadian clock gene polymorphisms and job stress on the risk of sleep disturbances.

RATIONALE: Sleep disturbances was associated with numerous adverse health outcomes. Many studies have reported that long-term exposure to job stress can lead to sleep disturbances, which may be influenced by genetic and environmental factors. OBJECTIVES: This cross-sectional study investigated whether circadian clock gene polymorphisms modulated the influence of job stress on sleep disturbances in a Chinese Han population, which to our best knowledge has not been explored. METHODS: The Effort-Reward Imbalance (ERI) scale and the Pittsburgh Sleep Quality Index (PSQI) were both used to access job stress and sleep disturbances. The SNaPshot SNP assay was carried out by screening for circadian clock gene polymorphisms in every participant. Interactions associated with sleep disturbances were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). RESULTS: Linear hierarchical regression analysis showed that job stress was significantly related to sleep disturbances. Likewise, our study found a significant effect of PER2 rs2304672 polymorphisms on sleep disturbances (p < 0.01), after controlling for confounding factors. In addition, the PER2 rs2304672 genotype modulated the relationship between job stress and sleep disturbances (ß = 0.414, p = 0.007). Interestingly, further analysis of the results of the PER2 gene rs2304672 × job stress interaction showed that rs2304672 G-allele carriers had a high-risk effect on sleep disturbances under high job stress. CONCLUSIONS: Our results suggest that the PER2 rs2304672 polymorphism may modulate the influence of job stress on sleep disturbances. These findings contribute to the field of sleep disturbances prevention and treatment.

Comparative Transcriptomic Analysis on White and Blue Flowers of Platycodon grandiflorus to Elucidate Genes Involved in the Biosynthesis of Anthocyanins.

BACKGROUND: Platycodon grandiflorus has long been used in Northeast Asia as a food and folk medicine to treat various diseases. The intense blue color of P. grandiflorus corolla is its characteristic feature. OBJECTIVES: By comparing deep transcriptomic data of P. grandiflorus and its white cultivar, we intended to elucidate the molecular mechanisms concerning the biosynthesis of anthocyanins in this plant. MATERIAL AND METHODS: We sampled blue mature flowers (PgB) and yellow young buds (PgY) of P. grandiflorus. Meanwhile, mature flowers (PgW) of P. grandiflorus white cultivar were also collected for RNA extraction and next-generation sequencing. After high-throughput sequencing, Trinity software was applied for de novo assembly and the resultant 49934 unigenes were subjected for expression analysis and annotation against NR, KEGG, UniProt, and Pfam databases. RESULTS: In all, 32.77 Gb raw data were generated and the gene expression profile for the flowers of P. grandiflorus was constructed. Pathway enrichment analysis demonstrated that genes involved in flavone and flavonol biosynthesis were differently expressed. CONCLUSIONS: The extremely low expression of flavonoid-3',5'-hydroxylase in PgY and PgW was regarded as the reason for the formation of its white cultivar. Our findings provided useful information for further studies into the biosynthetic mechanism of anthocyanins.

The complete chloroplast genome of Abutilon theophrasti medic (Malvaceae).

Abutilon theophrasti Medic is a traditional Chinese medicine, which can be seen nearly everywhere in China. In order to study its complete chloroplast genome, we collected leaves and obtained chloroplast genome information through next-generation sequencing. It showed that the genome whole length is 160,331 bp, resulted from 24,578,194 raw reads with 3,669,530,829 bases in total, and the GC contents ratio is 36.90%. Besides, the large single-copy region (LSC) is 89,006 bp, the small single-copy region (SSC) 20,149 bp, and inverted repeat (IR) 25,588 bp. The chloroplast genome encodes 76 genes, which contains 38 protein genes, five rRNA genes, and 33 tRNA. By conducting phylogenetic analysis for A.theophrasti, plants from genus Gossypium demonstrated close relationship with it.

Clinical features and prognostic factors of patients with COVID-19 in Henan Province, China.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19.

Pickled Vegetables Intake Impacts the Metabolites for Gastric Cancer.

PURPOSE: An increased risk of gastric cancer (GC) for pickled vegetables intake has been suggested, but a complete understanding of its pathogenic origin is still lacking, especially from a metabolic viewpoint. We investigated the plasma metabolites and metabolic pathway alteration of GC related to pickled vegetables intake. METHODS: We analyzed plasma samples collected from 365 gastric cancer patients and 347 healthy individuals, and divided them into three subgroups according to the intake of pickled vegetables. Plasma samples were detected by untargeted metabolomics. RESULTS: Nine metabolites were significantly altered in GC patients among pickled vegetables intake groups (FDR P-value<0.05). All of them were associated with the risk of gastric cancer adjusted for gender, age, smoking status, Helicobacter pylori infection. Pathway analysis showed significant alteration in the folate biosynthesis pathway. CONCLUSION: In short, we provide new insights from a metabolic perspective on the relationship between pickled vegetables intake and the occurrence of gastric cancer.

Enhancing the Interface Contact of Stacking Perovskite Solar Cells with Hexamethylenediammonium Diiodide-Modified PEDOT:PSS as an Electrode.

As an indispensable component of perovskite solar cells (PSCs), the commonly used Au and Ag electrodes still have some problems such as high cost and instability issues with regard to being corroded by iodide ions. In this paper, we report stacking perovskite solar cells (S-PSCs), which can avoid the use of precious metal electrodes and reduce the cost of devices and the requirements of equipment compared to conventional PSCs. The S-PSCs are composed of two semicells: a photoanode and a counter electrode (CE). For stacked devices, effective contact of the photoanode/CE interface is very important to the performance of the device. We used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the electrode and modified it by hexamethylenediammonium diiodide (HDADI2) to improve its physical and electrical properties. The surface of the HDADI2-modified PEDOT:PSS becomes rough and achieves higher adhesion, which enables the photoanode and CE to be sufficiently connected. In addition, the energy-level structure of the HDADI2-modified PEDOT:PSS matches better with that of the adjacent functional layers. Therefore, the S-PSCs performance has been significantly improved. Under an illumination area of 1 cm2, the power-conversion efficiency (PCE) of the S-PSCs can reach 15.21%. Moreover, the S-PSCs can be disassembled and assembled flexibly and repeatedly disassembled 500 times with almost no change in the PCE. This has a positive impact on cell maintenance and modular production.

Hexylammonium Iodide Derived Two-Dimensional Perovskite as Interfacial Passivation Layer in Efficient Two-Dimensional/Three-Dimensional Perovskite Solar Cells.

Defects locating within grain boundaries or on the film surface, especially organic cation vacancies and iodine vacancies, make the fabrication of perovskite solar cells (PSCs) with superior performance a challenge. Organic ammonium iodide is a promising candidate and has been frequently used to passivate these defects by forming two-dimensional (2D) perovskite. In this work, it is found that the chain length of organic ammonium iodide is a crucial factor on the defect passivation effect. Compared to butylammonium iodide, the hexylammonium iodide (HAI)-derived 2D perovskite is more efficient in decreasing interfacial defects, resulting in a notably enhanced photoluminescence lifetime and a more suppressed interfacial charge recombination process. As a consequence, the ultimate power conversion efficiency (PCE) has reached 20.62% (3D + HAI) as compared to 18.83% (3D). Moreover, the long-term durability of the corresponding PSCs against humidity and heat is simultaneously improved. This work once again demonstrates that the 2D/3D structure is promising for further improving the PCE and stability of PSCs.

LATS2 promotes apoptosis in non-small cell lung cancer A549 cells via triggering Mff-dependent mitochondrial fission and activating the JNK signaling pathway.

LATS2 is a classical tumor suppressor that affects non-small cell lung cancer proliferation and mobilization. However, its role in lung cancer cell apoptosis is unknown. The aim of our study is to explore whether LATS2 activates mitochondria-related apoptosis in lung cancer cells. In the present study, A549 non-small cell lung cancer cells were transfected with a LATS2 adenovirus to induce LATS2 overexpression. Cell apoptosis was evaluated via the MTT assay, TUNEL staining, western blotting, trypan blue staining and ELISA. Mitochondrial function was measured using an immunofluorescence assay, western blotting and ELISA. The results demonstrated that LATS2 was downregulated in A549 lung cancer cells. Overexpression of LATS2 induced A549 cell apoptosis via activating mitochondrial fission. Subsequently, we confirmed that LATS2 modulated mitochondrial fission via the JNK-Mff signaling pathway. Inhibition of the JNK pathway and/or knockdown of Mff abolished the pro-apoptotic effect of LATS2 on A549 cells. Taken together, our results identified LATS2 as a classical tumor suppressor of lung cancer via triggering mitochondrial fission and activating the JNK-Mff signaling pathway. Our results lay the foundation for detailed study of the molecular mechanisms of LATS2 overexpression and regulation of mitochondrial fission for lung cancer treatment.

Inhibition of Ep3 attenuates migration and promotes apoptosis of non-small cell lung cancer cells via suppression of TGF-ß/Smad signaling.

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Prostaglandin E2 (PGE2) regulates various biological processes, including invasion, proliferation and apoptosis. E-prostanoid 3 (Ep3) is a PGE2 receptor, and the functional role of Ep3 in the progression of NSCLC remains unresolved. The present study investigated the effects of Ep3 in A549 cells and explored the underlying molecular mechanisms. The results revealed that the mRNA and protein expression levels of Ep3 were significantly upregulated in NSCLC tissues and A549 cells. Pharmacological inhibition of Ep3 or RNA interference against Ep3 attenuated the cell viability, migration and invasion, and promoted apoptosis in A549 cells. Ep3 deficiency also decreased the expression of transforming growth factor (TGF)-ß, phosphorylated (p)-Smad2 and p-Smad3. The transfection of TGF-ß overexpression plasmids reversed the effects of Ep3 deficiency on the cell viability and apoptosis in A549 cells. Finally, an in vivo experiment revealed that Ep3-siRNA transfection strongly reduced the tumor growth and tumor volume. The Ep3-siRNA transfection also inhibited tumor metastasis via suppression of the expression of metastasis-associated proteins. Taken together, these findings indicate that inhibition of Ep3 attenuates the viability and migration, and promotes the apoptosis of NSCLC through suppression of the TGF-ß/Smad signaling pathway. Targeting of the Ep3/TGF-ß/Smad signaling pathway may be a novel therapeutic strategy for the prevention and treatment of NSCLC.

Bromine Doping as an Efficient Strategy to Reduce the Interfacial Defects in Hybrid Two-Dimensional/Three-Dimensional Stacking Perovskite Solar Cells.

Solar-to-electricity conversion efficiency, power conversion efficiency (PCE), and stability are two important aspects of perovskite solar cells (PSCs). However, both aspects are difficult to simultaneously enhance. In the recent two years, two-dimensional (2D)/three-dimensional (3D) stacking structure, designed by covering the 3D perovskite with a thin 2D perovskite capping layer, was reported to be a promising method to achieve both a higher PCE and improved stability simultaneously. However, when reducing the surface defects of 3D perovskite, the thin 2D capping layer itself may probably introduce additional interfacial defects in a 2D/3D stacking structure, which is thought to be able to trigger trap-assisted nonradiative recombination or ion migration. Thus, efforts should be paid to reduce the interfacial defects of 2D hybrid perovskite when serving as a modification layer in a 2D/3D stacking structure PSCs. Here, we demonstrate that bromine (Br) doping of the 2D perovskite capping layer is an efficient strategy to passivate interfacial defects robustly, by which the photoluminescence lifetime is enhanced notably, whereas the interfacial charge recombination is suppressed a lot. As a result, the PCE is enhanced from 18.01% (3D perovskite) to 20.07% (Br-doped 2D/3D perovskite) along with improved moisture stability.

Silver-Catalyzed Radical Arylphosphorylation of Unactivated Alkenes: Synthesis of 3-Phosphonoalkyl Indolines.

A silver-catalyzed phosphorylation/cyclization cascade of N-allyl anilines was developed, allowing direct access to 3-phosphonoalkyl indolines, which were previously obtainable only via tedious procedures under harsh/toxic conditions. The unactivated double bond serves as the radical acceptor, whereas H-phosphonates or -phosphine oxides act as the radical precursor. This protocol features simple operation, broad substrate scope, and great exo selectivity, and a gram-scale synthesis could be readily carried out.

Pseudohalogen-Based 2D Perovskite: A More Complex Thermal Degradation Mechanism Than 3D Perovskite.

(MA)2Pb(SCN)2I2, a new pseudohalogen-based 2D perovskite material, was reported as a very stable and promising photo-absorber in PSCs previously. However, the later researchers found that MA2Pb(SCN)2I2 was not as stable as claimed. Thus, it is very critical to clarify the controversy and reveal the degradation mechanism of MA2Pb(SCN)2I2. On the other hand, a large number of studies have indicated that adding a small amount of SCN- improves surface topography and crystallinity. However, whether SCN- ions can be incorporated into a 3D perovskite film remains debatable. In this work, the thermal degradation pathway of (MA)2Pb(SCN)2I2 is revealed by thermal gravimetric and differential thermal analysis coupled with quadrupole mass spectrometry and density functional theory calculations. The decomposition of (MA)2Pb(SCN)2I2 has been proved experimentally to be more complex than that of MAPbI3, involving four stages and multi-reactions from room temperature to above 500 °C. By combining the experimental results and theoretical calculations, it is found that 2D (MA)2Pb(SCN)2I2 actually is unstable when serving as photo-absorber in PSCs. Moreover, the role of SCN- in improving the crystallinity of 3D perovskite has also been discussed in detail.

Interplay between Exciton and Free Carriers in Organolead Perovskite Films.

For highly interested organolead perovskite based solar cells, the exciton and free carriers are the photoproducts in the working layers. In this study, we revealed their two forms of relations depending on heat-annealing condition. In non-annealed films and single crystal, they are in density-dependent dynamical balance (co-existing). For the sufficiently heat-annealed films, they present a significant emissive exciton-carrier collision (ECC). The two relations indicate the emergence of a subgrain morphology within the tetragonal phase of crystal grain, induced by heat annealing process. Such subgrain structure could be assigned to a ferroelastic twinning structure recently found inside the crystal grain of the films. Since the heat annealing is a general procedure in preparing perovskite working layers, we propose that the ECC and subgrain morphology widely exist in real devices. We suggest that the subgrain structure provides another level of morphological basis for in depth understanding high performance of organolead perovskite working layers.

SGK2 promotes hepatocellular carcinoma progression and mediates GSK-3ß/ß-catenin signaling in HCC cells.

The phosphoinositide 3-kinase pathway is one of the most commonly altered pathways in human cancers. The serum/glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2, and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. Few studies have investigated the role of SGK2 in hepatocellular carcinoma. Here, we report that SGK2 expression levels were upregulated in hepatocellular carcinoma tissues and human hepatoma cell lines compared to the adjacent normal liver tissues and a normal hepatocyte line, respectively. We found that downregulated SGK2 inhibits cell migration and invasive potential of hepatocellular carcinoma cell lines (SMMC-7721 and Huh-7).We also found that downregulated SGK2 suppressed the expression level of unphosphorylated (activated) glycogen synthase kinase 3 beta. In addition, SGK2 downregulation decreased the dephosphorylation (activation) of ß-catenin by preventing its proteasomal degradation in the hepatocellular carcinoma cell lines. These findings suggest that SGK2 promotes hepatocellular carcinoma progression and mediates glycogen synthase kinase 3 beta/ß-catenin signaling in hepatocellular carcinoma cells.

Knockdown of MDR1 increases the sensitivity to adriamycin in drug resistant gastric cancer cells.

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug- sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

Genome-wide analysis of primary auxin-responsive Aux/IAA gene family in maize (Zea mays. L.).

The phytohormone auxin is important in various aspects of organism growth and development. Aux/IAA genes encoding short-lived nuclear proteins are responsive primarily to auxin induction. Despite their physiological importance, systematic analysis of Aux/IAA genes in maize have not yet been reported. In this paper, we presented the isolation and characterization of maize Aux/IAA genes in whole-genome scale. A total of 31 maize Aux/IAA genes (ZmIAA1 to ZmIAA31) were identified. ZmIAA genes are distributed in all the maize chromosomes except chromosome 2. Aux/IAA genes expand in the maize genome partly due to tandem and segmental duplication events. Multiple alignment and motif display results revealed major maize Aux/IAA proteins share all the four conserved domains. Phylogenetic analysis indicated Aux/IAA family can be divided into seven subfamilies. Putative cis-acting regulatory DNA elements involved in auxin response, light signaling transduction and abiotic stress adaption were observed in the promoters of ZmIAA genes. Expression data mining suggested maize Aux/IAA genes have temporal and spatial expression pattern. Collectively, these results will provide molecular insights into the auxin metabolism, transport and signaling research.