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Respiratory syncytial virus (RSV) causes lower respiratory tract diseases and bronchiolitis in children and elderly individuals. There are no effective drugs currently available to treat RSV infection. In this study, we report that Licochalcone A (LCA) can inhibit RSV replication and mitigate RSV‐induced cell damage in vitro, and that LCA exerts a protective effect by reducing the viral titer and inflammation in the lungs of infected mice in vivo. We suggest that the mechanism of action occurs through pathways of antioxidant stress and inflammation. Further mechanistic results demonstrate that LCA can induce nuclear factor erythroid 2‐related factor 2 (Nrf2) translocation into the nucleus, activate heme oxygenase 1 (HO‐1), and inhibit reactive oxygen species‐induced oxidative stress. LCA also works to reverse the decrease in I‐kappa‐B‐alpha (IкBα) levels caused by RSV, which in turn inhibits inflammation through the associated nuclear factor kappa B and tumor necrosis factor‐α signaling pathways. The combined action of the two cross‐talking pathways protects hosts from RSV‐induced damage. To conclude, our study is the first of its kind to establish evidence of LCA as a viable treatment for RSV infection. [ABSTRACT FROM AUTHOR]

Constructing van der Waals (vdW) heterostructures provides an effective and feasible method for 2D materials to improve their properties and extend their possible applications. Using first-principles calculations, we explored the atomic and electronic structures of Janus In2SeX (X = S or Te) and revealed the existence of a vertical internal intrinsic electric field in these Janus monolayers. Then, we stacked the pristine InSe and Janus In2SeX (X = S or Te) with black phosphorus (BP) vertically to construct vdW heterostructures with a mismatch of less than 5% and systematically investigated their interface atomic structures and possible applications in photovoltaics. The calculation results reveal that the constructed vdW heterostructures can be synthesized experimentally, and the type-II band alignment can be found in all vdW heterostructures, which is independent of the internal electric field of Janus monolayers, the built-in dipole at the interface between two domains, and the number of layers. In addition, the vdW heterostructures show stronger light absorption compared to monolayer individuals, and the type-II band alignment can help the photo-excited carriers to separate and achieve an excellent photovoltaic power conversion efficiency of up to about 21% in these heterostructures. These extraordinary results suggest that these vdW heterostructures have great potential for more efficient solar photovoltaic applications. [ABSTRACT FROM AUTHOR]

Electrostatic control and van der Waals integration are useful methods for 2D materials to help modulate their properties. Here, we constructed nine types of monolayer and multilayer Janus structures based on group-III monochalcogenides and investigated their atomic and electronic structures from first-principles calculations. We found the existence of an intrinsic electric field at Janus structures by comparing their average vacuum electron potentials at two surfaces. Careful charge analyses reveal that the electric field at monolayer Janus structures is mainly due to the dipole of the bond that connects group-III elements of weaker negativity and group-VI elements of stronger negativity. The E-filed at multilayer Janus structures maintains owing to the superposition of dipole at each layer when layer numbers (LN) are not very large, and the electric field starts to reduce when LN is large enough and obvious charge transfer happens between two surfaces of Janus multilayers. Electronic structure calculations at Janus structures demonstrate that the electric field can hardly modulate the charge density population in the monolayer case, while the electric field will significantly bend the bands in multilayer cases and make the charge density of the valence band maximum and the conduction band minimum always located at two separating surfaces, which promotes electron–hole to separate. Furthermore, we investigated the band alignment of isolated monolayer pristine group-III monochalcogenides and isolated Janus group-III monochalcogenides of monolayer, bilayer, and trilayer, and constructed van der Waals (vdW) heterostructures with one pristine monolayer and one Janus monolayer. The results show that the surface termination of Janus structures at the interface can significantly influence the band offset and electronic structures of vdW heterostructures. These results can not only provide a new understanding of the intrinsic electric field of monolayer and multilayer 2D Janus structures but also give a guide that uses electrostatic to modulate the properties of group-III monochalcogenides and other 2D materials. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rice blast, caused by Magnaporthe oryzae, is a destructive disease threatening the production of staple foods worldwide. Quinone outside inhibitors (QoIs) are a group of chemicals exhibiting excellent activity against a majority of plant pathogens, with the disadvantage that pathogens can easily develop resistance to QoIs. RESULTS: Here, we investigated the activity of picoxystrobin against M. oryzae, which showed a great inhibitory effect on 100 strains of M. oryzae with half‐maximal effective concentrations (EC50) ranging from 0.0251 to 0.1337 μg ml−1. The EC50 values showed a continuous unimodal distribution that was identical to the normal distribution, suggesting the potency of our study to represent baseline sensitivity. In addition, nine resistant mutants were obtained by exposing M. oryzae to a high dosage of picoxystrobin in the laboratory; all of them showed cross‐resistance to the other five QoI fungicides. Although some mutants showed a decreased resistance factor after ten successive cultures on fungicide‐free medium, the resistance to picoxystrobin was still inheritable. Amino acid substitution of G143S was detected in eight of nine picoxystrobin‐resistant mutants, and G143A was detected in only one of nine mutants. A fitness penalty was found in the mutants carrying G143S rather than G143A. CONCLUSION: Our findings suggested that M. oryzae had a mid to high risk of resistance to picoxystrobin. Considering this, we should be vigilant to the resistance risk and apply picoxystrobin sensibly in the field. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide (scCO2)–assisted annealing process has demonstrated promising prospects in the toughness enhancement of polymers. Herein, this effective method was adopted to toughen a biodegradable polymer, poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV). Significantly, the greatly improved tensile toughness and impact toughness of PHBV were achieved. It is noted that the 26 times enhancement in tensile toughness and 2.4 times improvement in impact toughness were obtained for the sample treated at annealing temperature of 90°C and saturation pressure of 10 MPa. More importantly, the toughness mechanism was further explored via various characterizations. It is indicated that the increment in the toughness of PHBV after scCO2‐assisted annealing was closely related to the perfection of microstructure sample and the appearance of micro‐voids. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) may have phenotypic effects by altering the expression level of the gene(s) or regulatory element(s) contained. It is believed that CNVs play pivotal roles in controlling plant architecture and other traits in plant. However, the effects of CNV contributing to special traits remain largely unknown. Here we report a CNV involved in rice architecture by modulating tiller number and leaf angle. In the genome of Oryza sativa ssp. japonica cv. Nipponbare, we found a locus Loc_Os08g34249 is derived from a 13,002-bp tandem duplication in the nearby region of OsMTD1 , a gene regulating tillering in rice. Further survey of 230 rice cultivars showed that the duplication occurred in only 13 japonica rice cultivars. Phenotypic investigation indicated that this CNV region may contribute to tiller number. Moreover, we revealed that OsMTD1 not only influences rice tiller number and leaf angle, but also represses pri-miR156f transcription in the CNV region. Intriguingly, this CNV performs function through both the dosage and position effects on OsMTD1 and pri-miR156f. Thus, our work identified a CNV and revealed a molecular regulatory basis for its effects on plant architecture, implying this CNV may possess importance and application potential in molecular breeding in rice. [ABSTRACT FROM AUTHOR]

A highly reliable high-performance liquid chromatography method was developed and validated for determining quality of extracts from the leaves ofDipsacus sativus(Linn.) Honck. Under optimum conditions, the chromatography profile of eight compounds was collected, with compound saponarin as marker. The analysis results indicated that saponarin and isovitexin were the main active components. Pharmacological experiments proved that extracts from the leaves showed significant antioxidant activity. This work could serve to validate the usefulness of high-performance liquid chromatography analyses in traditional Chinese medicine. [ABSTRACT FROM PUBLISHER]

Drug administration via buccal mucosa is an attractive drug delivery strategy due to good patient compliance, prolonged localized drug effect, and avoidance of gastrointestinal drug metabolism and first-pass elimination. Buccal drug delivery systems need to maintain an intimate contact with the mucosa lining in the wet conditions of the oral cavity for long enough to allow drug release and absorption. For decades, mucoadhesive polymers such as chitosan (CS) and its derivatives have been explored to achieve this. In this study, inspired by the excellent wet adhesion of marine mussel adhesive protein, we developed a buccal drug delivery system using a novel catechol-functionalized CS (Cat-CS) hydrogel. We covalently bonded catechol functional groups to the backbone of CS, and crosslinked the polymer with a non-toxic crosslinker genipin (GP). We achieved two degrees of catechol conjugation (9% and 19%), forming Cat9-CS/GP and Cat19-CS/GP hydrogels, respectively. We confirmed covalent bond formation during the catechol functionalization and GP crosslinking during the gel formation. The gelation time and the mechanical properties of Cat-CS hydrogels are similar to those of CS only hydrogels. Catechol groups significantly enhanced mucoadhesion in vitro (7 out of the 10 Cat19-CS hydrogels were still in contact with porcine mucosal membrane after 6 h, whereas all of the CS hydrogels lost contact after 1.5 h). The new hydrogel systems sustained the release of lidocaine for about 3 h. In-vivo, we compared buccal patches made of Cat19-CS/GP and CS/GP adhered to rabbit buccal mucosa. We were able to detect lidocaine in the rabbit's serum at concentration about 1 ng/ml only from the Cat19-CS patch, most likely due to the intimate contact provided by mucoadhesive Cat19-CS/GP systems. No inflammation was observed on the buccal tissue in contact with any of the patches tested. These results show that the proposed catechol-modified CS hydrogel is a promising mucoadhesive and biocompatible hydrogel system for buccal drug delivery. [ABSTRACT FROM AUTHOR]

Fluxapyroxad, a broad-spectrum and high-efficiency succinate dehydrogenase inhibitor (SDHI) fungicide, can control plant pathogens on many crops. However, no data about the fungicidal activity of fluxapyroxad against Stemphylium solani and its resistance risk are available. In this study, the mycelial growth inhibition method was used to determine the sensitivity of 99 S. solani strains to fluxapyroxad. The EC 50 values ranged from 0.0183 to 0.3017 μg/mL, with an average EC 50 value of 0.0839 ± 0.0051 μg/mL. The results indicated that fluxapyroxad exhibited an excellent inhibitory efficacy against S. solani. Six resistant mutants were obtained by laboratory fungicide taming. The resistance ratio of each mutant was greater than 50 and the resistance of the mutants to fluxapyroxad was steadily inheritable through 10 successive culture transfers to fungicide-free PSA plates. We found that fluxapyroxad resistance not only affected mycelial growth in S. solani , but was also temperature dependent. Moreover, fluxapyroxad resistance caused markedly decreased virulence of S. solani on detached tomato leaves, indicating that the resistant mutants suffered a fitness penalty. Cross-resistance analysis showed that no cross-resistance was observed between fluxapyroxad and fludioxonil, iprodione, azoxystrobin or fluazinam, while a positive cross-resistance was observed between fluxapyroxad and pydiflumetofen. We concluded that the resistance of S. solani to fluxapyroxad was moderate risk. Therefore, fluxapyroxad is recommended as a potential candidate for controlling tomato gray leaf spot caused by S. solani. • Fluxapyroxad exhibited an excellent in vitro antifungal activity against Stemphylium solani. • The resistance of Stemphylium solani to fluxapyroxad was classified as moderate risk. • There was a positive cross-resistance between fluxapyroxad and pydiflumetofen against Stemphylium solani. • Fluxapyroxad is recommended as a potential candidate for controlling tomato gray leaf spot caused by Stemphylium solani. [ABSTRACT FROM AUTHOR]

Chitosan (CH), partially N-deacetylatedchitin, is a biodegradable and biocompatible polymer that has showngreat potential in drug delivery and tissue engineering applications.Although bioadhesive, CH has limited mucoadhesion in wet conditionsdue to weak interactions with biological surfaces. DOPA (3,4-dihydroxy-l-phenylalanine), a catechol-containing molecule naturally presentin marine mussel foot proteins, has been shown to increase the mucoadhesionof several polymers. We report here a simple and bioinspired approachto enhance CH mucoadhesion in wet conditions by preparing mixed hydrogelsincluding CH and different catechol-containing compounds, namely DOPA,hydrocaffeic acid (HCA), and dopamine (DA). We characterized the hydrogelsfor their swelling, release kinetics of the catechol compounds, andmucoadhesive strength to rabbit small intestine. The swelling of thehydrogels was pH dependent with maximum swelling at pH 1. The hydrogelswelling was higher in the presence of the DOPA and DA but lower inthe presence of HCA. HCA/CH hydrogel also showed the slowest catecholrelease, most likely due to electrostatic interactions between CHand HCA. Lower hydrogel swelling and slower HCA release resulted inincreased mucoadhesion: HCA/CH showed more than 2-fold enhancementof mucoadhesion to rabbit small intestine compared to CH alone. Sinceit is known that catechol compounds can be oxidized, we analyzed theoxidation of DOPA, HCA, and DA at different pH values and its effecton mucoadhesion. We found that oxidation occurring before contactwith the intestinal mucosa did not improve mucoadhesion, while oxidationoccurring during the contact further increased the mucoadhesion ofHCA/CH hydrogels. These results show that mucoadhesion of CH hydrogelscan be increased with a simple bioinspired approach, which has thepotential to be applied to other polymers since it does not requireany chemical modification. [ABSTRACT FROM AUTHOR]

This study intended to investigate the role of microRNA-27b (miR-27b) in proliferation of oral squamous cell carcinoma (OSCC) cells and to explore the potential molecular mechanism. Cell proliferation was detected by MTT assay. The expression levels of miR-27b, Frizzled7 ( FZD7 ), cyclin D1 and c-myc were detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression level of FZD7 was detected by western blot analysis. The relationship between miR-27b and FZD7, and the activity of Wnt signaling pathway were determined using luciferase reporter assay. The miR-27b expression in OSCC cell lines was significantly decreased compared with control. Overexpression of miR-27b remarkably inhibited OSCC cell proliferation. Additionally, miR-27b could target and inhibit FZD7 expression and decrease the activity of Wnt signaling pathway.miR-27b could inhibit OSCC cell proliferation through inhibiting FZD7 and FZD7-mediated Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia., Aim of the Study: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO., Materials and Methods: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR., Results: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID 50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 μg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment., Conclusions: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Wheat crown rot (WCR), primarily caused by Fusarium pseudograminearum has become more and more prevalent in winter wheat areas in China. However, limited fungicides have been registered for the control of WCR in China so far. Pyraclostrobin is a representative quinone outside inhibitor (QoI) with excellent activity against Fusarium spp. There is currently limited research on the resistance risk and resistance mechanism of F. pseudograminearum to pyraclostrobin., Results: Here, we determined the activity of pyraclostrobin against F. pseudograminearum. The EC 50 values ranged from 0.022 to 0.172 μg mL -1 with an average EC 50 value of 0.071 ± 0.030 μg mL -1 . Four highly pyraclostrobin-resistant mutants were obtained from two sensitive strains by ultraviolet (UV) mutagenesis in the laboratory. The mutants showed decreased mycelial growth rate and virulence as compared with the corresponding wild-type strains, indicating that pyraclostrobin resistance suffered a fitness penalty in F. pseudograminearum. It was found that the high resistance of four mutants was caused by the G143S mutation in Cytb. Molecular docking analysis also further confirms that the G143S mutation in Cytb decreased the binding affinity between pyraclostrobin and Cytb., Conclusion: The resistance risk of F. pseudograminearum to pyraclostrobin could be low to medium. Although a mutation at the G143S position of Cytb could potentially occur, this mutation decreases the fitness of the mutant, which may reduce its survival in the environment. Therefore, the negative consequences of a possible mutation are lower. This makes pyraclostrobin a good candidate for controlling crown rot in wheat. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Both lung and gut belong to the common mucosal immune system (CMIS), with huge surface areas exposed to the external environment. They are the main defense organs against the invasion of pathogens and play a key role in innate and adaptive immunity. Recently, more and more evidence showed that stimulation of one organ can affect the other, as exemplified by intestinal complications during respiratory disease and vice versa , which is called lung-gut crosstalk. Intestinal microbiota plays an important role in respiratory and intestinal diseases. It is known that intestinal microbial imbalance is related to inflammatory bowel disease (IBD), this imbalance could impact the integrity of the intestinal epithelial barrier and leads to the persistence of inflammation, however, gut microbial disturbances have also been observed in respiratory diseases such as asthma, allergy, chronic obstructive pulmonary disease (COPD), and respiratory infection. It is not fully clarified how these disorders happened. In this review, we summarized the latest examples and possible mechanisms of lung-gut crosstalk in respiratory disease and IBD and discussed the strategy of shaping intestinal flora to treat respiratory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Fu, Han, Sun, Xu, Yang and Rong.)

Constructing van der Waals (vdW) heterostructures provides an effective and feasible method for 2D materials to improve their properties and extend their possible applications. Using first-principles calculations, we explored the atomic and electronic structures of Janus In 2 SeX (X = S or Te) and revealed the existence of a vertical internal intrinsic electric field in these Janus monolayers. Then, we stacked the pristine InSe and Janus In 2 SeX (X = S or Te) with black phosphorus (BP) vertically to construct vdW heterostructures with a mismatch of less than 5% and systematically investigated their interface atomic structures and possible applications in photovoltaics. The calculation results reveal that the constructed vdW heterostructures can be synthesized experimentally, and the type-II band alignment can be found in all vdW heterostructures, which is independent of the internal electric field of Janus monolayers, the built-in dipole at the interface between two domains, and the number of layers. In addition, the vdW heterostructures show stronger light absorption compared to monolayer individuals, and the type-II band alignment can help the photo-excited carriers to separate and achieve an excellent photovoltaic power conversion efficiency of up to about 21% in these heterostructures. These extraordinary results suggest that these vdW heterostructures have great potential for more efficient solar photovoltaic applications.

Polysaccharides are important natural biomacromolecules. In particular, microbial exopolysaccharides have received much attention. They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. In this study we aimed to further enhance exopolysaccharide production by systemic fermentation optimization. By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L -1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g -1 and a productivity of 1.24 g L -1  h -1 . Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L -1 , with a glucose yield of 0.60 g g -1 and a productivity of 1.29 g L -1  h -1 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Xu, Zeng, Shan and Zhou.)

Two-dimensional materials with excellent surface-volume ratios and massive reaction sites recently have been receiving attention for gas sensing. With first-principles calculations, we explored the performance of monolayer Sc 2 CF 2 as a gas sensor. We investigated how molecule adsorption affects its electronic structure and optical properties. It is found that a large charge transfer quantity happens between Sc 2 CF 2 and NO 2 , which results from the fact that the lowest unoccupied molecular orbital (LUMO) of NO 2 is below the valence band maximum (VBM) of Sc 2 CF 2 . Moreover, the MD simulation shows that NO 2 can adsorb on the Sc 2 CF 2 surface stably at room temperature. We explored the effect of biaxial strain on the adsorption energy and charge transfer quantity of each system, and the results show that the biaxial strain can enhance both the adsorption energy and charge transfer quantity of the NO 2 system and thus can improve the sensitivity of Sc 2 CF 2 in detecting the NO 2 molecule. Furthermore, we investigated the adsorption behavior and charge transfer of polar polyatomic molecules at the Sc 2 CF 2 surface with h -BN as a substrate, and the results demonstrate that the h -BN substrate can hardly modify the main results. Our result predicts that Sc 2 CF 2 can be a promising selective and sensitive sensor to detect the NO 2 molecule, and could also give a theoretical guide for other terminated MXenes used for gas sensors or detectors., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

KIAA0101, previously identified as PCNA-associated factor, is overexpressed among almost majority of human cancers and has emerged as an important regulator of cancer progression; however, its function in human nasopharyngeal carcinoma (NPC) remain unknown. Integrated bioinformatics approaches were employed to determine the KIAA0101 expressions in the NPC samples. Lentiviral vectors carrying KIAA0101 shRNA were constructed and stable transfected cells were validated by qRT-PCR and western blot. Cellular functions were then evaluated by MTT, colony formation, Brdu staining, and flow cytometry. Mechanistic studies were systematically investigated by UCSC Genome Browser, GEO, UALCAN, QIAGEN, PROMO and JASPAR, ChIP, and the cBioPortal, et al. The results showed that KIAA0101 ranked top overexpressed gene lists in GSE6631 dataset. KIAA0101 was highly expressed in NPC tissues and cell lines. Furthermore, knockdown of KIAA0101 significantly inhibited cell proliferation and DNA replication, promoted apoptosis and cell cycle arrest in vitro. Meanwhile, the mechanistic study revealed that MAP kinase phosphorylation-dependent activation of ELK1 may enhance neighbor gene expressions of KIAA0101 and TRIP4 by binding both promotor regions in the NPC cells. Taken together, our findings indicate that overexpression of KIAA0101 activated by MAP kinase phosphorylation-dependent activation of ELK1 may play an important role in NPC progression.

The selection of scaffold materials and the optimization of scaffold morphological and mechanical properties are critical for successful bone tissue engineering. We fabricated porous scaffolds of nano-sized zirconia using a replication technique. The study aimed to explore the relationship between porosity, pore size, mechanical strength, cell adhesion, and cell proliferation in the zirconia scaffolds. Macro- and micro-structures and compressive strength were comparatively tested. Beagle bone marrow stromal cells were seeded onto the scaffolds to evaluate cell seeding efficiency and cell proliferation profile over 14 d of incubation. The zirconia scaffolds presented a complex porous structure with good interconnectivity of pores. By increasing the sinter cycles, the porosity and pore size of the scaffolds decreased, with mean values ranging from 92.7-68.0% and 830-577 μm, respectively, accompanied by increased compressive strengths of 0.6-4.4 MPa. Cell seeding efficiency and cell proliferation over the first 7 d of incubation increased when the porosity decreased, with cell viability highest in the scaffold with a porosity of 75.2%. After 7 d of incubation, the cell proliferation increased when the porosity increased, highest in the scaffolds with a porosity of 92.7%. These results showed that the zirconia scaffold with a porosity of 75.2% possesses favorable mechanical and biological properties for future applications in bone tissue engineering.

Cancer stem cells (CSCs) may contribute to tumor initiation, distant metastasis and chemo-resistance. One of RNA-binding proteins, Quaking (QKI), was reported to be a tumor suppressor. Here we showed that reduced QKI levels were observed in many human oral cancer samples. Moreover further reduction of QKI expression in CSCs was detected compared with non-CSCs in oral cancer cell lines. Overexpressing QKI in oral cancer cells significantly reduced CSC sphere formation and stem cell-associated genes. In tumor implanting nude mice model, QKI significantly impeded tumor initiation rates, tumor sizes and lung metastasis rates. As a contrast, knocking down QKI enhanced the above effects. Among the putative CSC target genes, SOX2 expression was negatively affected by QKI, mechanism study revealed that QKI may directly regulate SOX2 expression via specific binding with its 3'UTR in a cis element-dependent way. Loss of SOX2 even completely reversed the sphere forming ability in QKI knockdown cell line. Taken together, these data demonstrated that SOX2 is an important CSC regulator in oral cancer. QKI is a novel CSC inhibitor and impaired multiple oral CSC properties via partial repression of SOX2. Therefore, reduced expression of QKI may provide a novel diagnostic marker for oral cancer.

Background Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that is activated by fibrillar collagens. Although DDR2 contributes to the metastasis of some tumors, its role in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to investigate the expression level, clinical and pathological significance, and biologic function of DDR2 in HNSCC. Methods Real-time quantitative PCR, western blot, and immunohistochemical staining were employed to assess the expression levels of DDR2 in HNSCC specimens. Adenovirus-mediated overexpression of DDR2 was used to evaluate its consequences on cell proliferation, invasion, migration, and the process of hypoxia-induced epithelial-mesenchymal transition (EMT). Then nude mouse xenograft and tail vein metastasis models were utilized to validate the in vitro results. Results DDR2 was highly expressed in high grade HNSCC tissues and lowly expressed in low grade HNSCC tissues, but absent or rarely expressed in cancer-associated normal tissues. Both the frequency and expression intensity of DDR2 were significantly associated with tumor pathologic stage and lymph node metastasis. In vitro, DDR2 overexpression in HNSCC cells failed to alter cell proliferation but markedly accelerates cell invasion and migration as well as hypoxia-induced EMT. In vivo, elevated expression of DDR2 speeds up the metastasis of HNSCC cells to the lung. Conclusion DDR2 plays an important role in HNSCC metastasis, and might be a promising target for future therapies in this type of cancer.