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Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.

A major racial disparity in prostate cancer (PCa) is that African American (AA) patients have a higher mortality rate than European American (EA) patients. We filtered the SEER 2009–2011 records and divided them into four groups regarding patient races and cancer grades. On such a partition, we performed a series of statistical analyses to further clarify the aforementioned disparity. Molecular evidence for a primary result of the epidemiological analysis was obtained from gene expression data. The results include: (1) Based on the registry-specific measures, a significant linear regression of total mortality rate (as well as PCa specific mortality rate) on the percentage of (Gleason pattern-based) high-grade cancers (PHG) is demonstrated in EAs (p

Fusarium wilt in faba bean (Vicia faba L.) is caused by Fusarium oxysporum f. sp. fabae (FOF), which reduces the yield of crop. We used greenhouse, field and laboratory experiments to evaluate the role of organic acids in the occurrence of Fusarium wilt of faba bean to confirm the mechanism of rational application of nitrogen (N) and intercropping to alleviate Fusarium wilt. We investigated the response of organic acids exuded from the roots of faba bean to different N levels and cropping patterns (monocropping and intercropping with wheat). The results showed that the application of N and intercropping with wheat could control the Fusarium wilt of faba bean, which was closely related to the components and quantity of organic acids exuded from its roots. Among them, tartaric acid and malic acid are the most abundant and important, because they have a significant inhibitory effect on the growth and reproduction of FOF and substantially aid in the control of Fusarium wilt. The application of 90 kg ha−1 of N combined with wheat intercropping significantly controlled the Fusarium wilt and increased the grain yield of faba bean. Our results suggest that 90 kg ha−1 of N combined with intercropping is the most effective way to control Fusarium wilt and should be incorporated into agricultural management practices.

In the present work, Ag@AgCl-reinforced cellulose composites with enhanced antibacterial and photocatalytic degradation properties were successfully synthesized via oil bath heating method. During the process, zinc chloride (ZnCl2) solution was used as both Cl− resource to form AgCl and the solvent to dissolve cellulose. The samples were synthesized with different temperatures, times, and concentrations of ZnCl2 solution. The morphology, microstructure and phase of the as-prepared samples were analyzed with X-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectrometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), photocatalytic activity studies and inhibition zone experiments. Results showed that dye solution could be completely degraded by the materials in 1 h, and higher concentrations of ZnCl2 solution favored for larger inhibition zones (higher to 10.8 mm). This synthetic strategy displayed here offers more possibilities to high value-added applications of cellulose.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240–370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

The ventral tegmental area (VTA) projection to the nucleus accumbens shell (NAcSh) regulates NAcSh-mediated motivated behaviors in part by modulating the glutamatergic inputs. This modulation is likely to be mediated by multiple substances released from VTA axons, whose phenotypic diversity is illustrated here by ultrastructural examination. Furthermore, we show in mouse brain slices that a brief optogenetic stimulation of VTA-to-NAc projection induced a transient inhibition of excitatory postsynaptic currents (EPSCs) in NAcSh principal medium spiny neurons (MSNs). This inhibition was not accompanied by detectable alterations in presynaptic release properties of electrically-evoked EPSCs, suggesting a postsynaptic mechanism. The VTA projection to the NAcSh releases dopamine, GABA and glutamate, and induces the release of other neuronal substrates that are capable of regulating synaptic transmission. However, pharmacological inhibition of dopamine D1 or D2 receptors, GABAA or GABAB receptors, NMDA receptors, P2Y1 ATP receptors, metabotropic glutamate receptor 5, and TRP channels did not prevent this short-term inhibition. These results suggest that an unknown mechanism mediates this form of short-term plasticity induced by the VTA-to-NAc projection.

The Musashi family of RNA binding proteins act to promote stem cell self-renewal and oppose cell differentiation predominantly through translational repression of mRNAs encoding pro-differentiation factors and inhibitors of cell cycle progression. During tissue development and repair however, Musashi repressor function must be dynamically regulated to allow cell cycle exit and differentiation. The mechanism by which Musashi repressor function is attenuated has not been fully established. Our prior work indicated that the Musashi1 isoform undergoes site-specific regulatory phosphorylation. Here, we demonstrate that the canonical Musashi2 isoform is subject to similar regulated site-specific phosphorylation, converting Musashi2 from a repressor to an activator of target mRNA translation. We have also characterized a novel alternatively spliced, truncated isoform of human Musashi2 (variant 2) that lacks the sites of regulatory phosphorylation and fails to promote translation of target mRNAs. Consistent with a role in opposing cell cycle exit and differentiation, upregulation of Musashi2 variant 2 was observed in a number of cancers and overexpression of the Musashi2 variant 2 isoform promoted cell transformation. These findings indicate that alternately spliced isoforms of the Musashi protein family possess distinct functional and regulatory properties and suggest that differential expression of Musashi isoforms may influence cell fate decisions.

Current opinions about the effect of intensive blood pressure (BP) reduction for acute intracerebral hemorrhage (ICH) are inconsistent. We performed a meta-analysis to evaluate the efficacy and safety of intensive BP reduction for acute ICH by analyzing data from several recent randomized controlled trials (RCTs). There were six eligible studies that met the inclusion criteria, for a total of 4,385 acute ICH patients in this meta-analysis. After analyzing these data, we found differences between intensive and standard BP lowering treatment groups in total mortality rates, unfavorable outcomes, hematoma expansion, neurologic deterioration, and severe hypotension were not significant. Moreover, compared with the standard treatment, the rate of renal adverse event in intensive treatment group was significantly higher. The intensive treatment approach was recommended in the following situations: (1) longer prehospital duration; (2) lower National Institute of Health stroke scale (NIHSS) score; (3) no hypertension history.

We aim to perform a systematic review and meta-analysis to examine the prognostic value of decompressive craniectomy (DC) in patients with traumatic intracranial hypertension. PubMed, EMBASE, Cochrane Controlled Trials Register, Web of Science, http://clinicaltrials.gov/ were searched for eligible studies. Ten studies were included in the systematic review, with four randomized controlled trials involved in the meta-analysis, where compared with medical therapies, DC could significantly reduce mortality rate [risk ratio (RR), 0.59; 95% confidence interval (CI), 0.47–0.74, P P P P = 0.02), but increase complications rate (RR, 1.94; 95% CI, 1.31–2.87, P P = 0.33), while in subgroup analysis, early DC would possibly result in improved prognosis (P = 0.04). Results from observational studies supported pooled results except prolonged length of ICU and hospital stay. Conclusively, DC seemed to effectively lower ICP, reduce mortality rate but increase complications rate, while its benefit on functional outcomes was not statistically significant.

There is currently a pandemic of pseudorabies virus (PRV) variant strains in China. Despite extensive research on PRV variant strains in the past two years, few studies have investigated PRV pathogenicity-related genes. To determine which gene(s) is/are linked to PRV virulence, ten putative virulence genes were knocked out using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 technology. The pathogenicity of these mutants was evaluated in a mouse model. Our results demonstrated that of the ten tested genes, the thymidine kinase (TK) and glycoprotein M (gM) knockout mutants displayed significantly reduced virulence. However, mutants of other putative virulence genes, such as glycoprotein E (gE), glycoprotein I (gI), Us2, Us9, Us3, glycoprotein G (gG), glycoprotein N (gN) and early protein 0 (EP0), did not exhibit significantly reduced virulence compared to that of the wild-type PRV. To our knowledge, this study is the first to compare virulence genes from the current pandemic PRV variant strain. This study will provide a valuable reference for scientists to design effective live attenuated vaccines in the future.

Inhibition of amyloid β-protein (Aβ) aggregation is considered as a promising strategy for the prevention and treatment of Alzheimer’s disease. Epigallocatechin-3-gallate (EGCG) and curcumin have been recognized as effective inhibitors of Aβ aggregation. Herein, we proposed dual-inhibitor modification of hyaluronic acid (HA) to explore the synergistic effect of the two inhibitors. EGCG-modified HA (EHA) formed dispersed hydrogel structures, while EGCG-curcumin bi-modified HA (CEHA) self-assembled into nanogels like curcumin-modified HA (CHA). Thioflavin T fluorescent assays revealed that the inhibitory effect of CEHA was 69% and 55% higher than EHA and CHA, respectively, and cytotoxicity assays showed that the viability of SH-SY5Y cells incubated with Aβ and CEHA was 28% higher than that with Aβ and the mixture of EHA and CHA. These results clearly indicate the synergism of the two inhibitors. It is considered that the difference in the hydrophobicities of the two inhibitors made the bi-modification of HA provide a favorable CEHA nanostructure that coordinated different inhibition effects of the two inhibitors. This research indicates that fabrication of dual-inhibitor nanosystem is promising for the development of potent agents against Aβ aggregation and cytotoxicity.

Coptidis Rhizoma binds to the membrane receptors on hPDLSC/CMC, and the active ingredient Berberine (BER) that can be extracted from it may promote the proliferation and osteogenesis of periodontal ligament stem cells (hPDLSC). The membrane receptor that binds with BER on the cell surface of hPDLSC, the mechanism of direct interaction between BER and hPDLSC, and the related signal pathway are not yet clear. In this research, EGFR was screened as the affinity membrane receptor between BER and hPDLSC, through retention on CMC, competition with BER and by using a molecular docking simulation score. At the same time, the MAPK PCR Array was selected to screen the target genes that changed when hPDLSC was simulated by BER. In conclusion, BER may bind to EGFR on the cell membrane of hPDLSC so the intracellular ERK signalling pathways activate, and nuclear-related genes of FOS change, resulting in the effect of osteogenesis on PDLSC.

Irradiated bone has a greater risk of implant failure than nonirradiated bone. The purpose of this study was to investigate the influence of cell sheets composed of co-cultured bone marrow mesenchymal stromal cells (BMSCs) and endothelial progenitor cells (EPCs) on implant osseointegration in irradiated bone. Cell sheets (EPCs, BMSCs or co-cultured EPCs and BMSCs) were wrapped around titanium implants to make cell sheet-implant complexes. The co-cultured group showed the highest osteogenic differentiation potential in vitro, as indicated by the extracellular matrix mineralization and the expression of osteogenesis related genes at both mRNA and protein levels. The co-cultured cells promoted ectopic bone formation as indicated by micro-computed tomography (Micro-CT) and histological analysis. In the irradiated tibias of rats, implants of the co-cultured group showed enhanced osseointegration by Micro-CT evaluation and histological observation. Co-cultured EPCs and BMSCs also up-regulated the expression of osteogenesis related genes in bone fragments in close contact with implants. In conclusion, cell sheets of co-cultured EPCs and BMSCs could promote osseous healing around implants and are potentially useful to improve osseointegration process for patients after radiotherapy.

Motivated by the fabrication of layered two-dimensional material C2N-h2D [Nat. Commun. 6, 6486 (2015)], we cut the single-layer C2N-h2D into a zigzag nanoribbon and perform a theoretical study. The results indicate that the band structure changes from semiconducting to metallic and a negative differential resistance effect occurs in the I-V curve. Interestingly, the current can be reduced to zero and this insulator-like state can be maintained as the bias increases. We find this unique property is originated from a peculiar band morphology, with only two subbands appearing around the Fermi level while others being far away. Furthermore the width and symmetry of the zigzag C2N-h2D nanoribbon can be used to tune the transport properties, such as cut-off bias and the maximum current. We also explore the electron transport property of an aperiodic model composed of two nanoribbons with different widths and obtain the same conclusion. This mechanism can be extended to other systems, e.g., hybrid BCN nanoribbons. Our discoveries suggest that the zigzag C2N-h2D nanoribbon has great potential in nanoelectronics applications.

Irreversible white spot lesion (WSL) occurs in up to 50% of patients during orthodontic treatment. Therefore, orthodontic adhesives need to be able to inhibit or reduce bacterial growth in order to prevent or minimize WSL. This study evaluated the antibacterial effect and shear bond strength (SBS) of a resin-based orthodontic adhesive containing the antibacterial monomer 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB). MAE-HB was added at three concentrations (1, 3, and 5 wt%) to a commercial orthodontic adhesive Transbond XT, while the blank control comprised unmodified Transbond XT. Their antibacterial effects on Streptococcus mutans were investigated after 0 and 180 days of aging. The SBS of metal brackets bonded to the buccal enamel surface of human premolars was assessed. Compared with the blank control, the MAE-HB-incorporated adhesive exhibited a significant contact inhibitory effect on the growth of S. mutans (P

A large number of studies have demonstrated that autophagy is involved in the infection processes of different pathogens. Autophagy is now recognized as an essential component of innate and adaptive immunity. Several herpesviruses have developed various strategies to evade this antiviral mechanism. Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes devastating disease in infected pigs. In this study, we described the interaction between PRV and autophagy for the first time. PRV infection had a dual effect on the cell autophagy response; during the early period of infection, PRV virions induced autophagy without viral replication, and with viral protein expression, PRV reduced the basal level of autophagy in several permissive cells. We observed that inhibit the level of autophagy could increase the titer of infectious PRV. We also found that the conserved alphaherpesvirus US3 tegument protein may reduce the level of autophagy via activation of the AKT/mTOR pathways in PRV infected cells. These findings suggest that autophagy likely contributes to clearance of PRV, and that the virus has evolved strategies to antagonize this pathway.

Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P 0.05). No significant differences in the antibacterial activities of eluents from control versus 10%-MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P S. mutans.

Sn is a classical superconductor on the border between type I and type II with critical temperature of 3.7 K. We show that its critical parameters can be dramatically increased if it is brought in the form of loosely bound bundles of thin nanowires. The specific heat displays a pronounced double phase transition at 3.7 K and 5.5 K, which we attribute to the inner ‘bulk’ contribution of the nanowires and to the surface contribution, respectively. The latter is visible only because of the large volume fraction of the surface layer in relation to the bulk volume. The upper transition coincides with the onset of the resistive transition, while zero resistance is gradually approached below the lower transition. In contrast to the low critical field Hc = 0.03 T of Sn in its bulk form, a magnetic field of more than 3 T is required to fully restore the normal state.

Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2* signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk.

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration.

Effective pulp-capping materials must have antibacterial properties and induce dentin bridge formation; however, many current materials do not satisfy clinical requirements. Accordingly, the effects of an experiment pulp-capping material (Exp) composed of an antibacterial resin monomer (MAE-DB) and Portland cement (PC) on the viability, adhesion, migration, and differentiation of human dental pulp stem cells (hDPSCs) were examined. Based on a Cell Counting Kit-8 assay, hDPSCs exposed to Exp extracts showed limited viability at 24 and 48 h, but displayed comparable viability to the control at 72 h. hDPSC treatment with Exp extracts enhanced cellular adhesion and migration according to in vitro scratch wound healing and Transwell migration assays. Exp significantly upregulated the expression of osteogenesis-related genes. The hDPSCs cultured with Exp exhibited higher ALP activity and calcium deposition in vitro compared with the control group. The novel material showed comparable cytocompatibility to control cells and promoted the adhesion, migration, and osteogenic differentiation of hDPSCs, indicating excellent biocompatibility. This new direct pulp-capping material containing MAE-DB and PC shows promise as a potential alternative to conventional materials for direct pulp capping.

The Pheretima complex within the Megascolecidae family is a major earthworm group. Recently, the systematic status of the Pheretima complex based on morphology was challenged by molecular studies. In this study, we carry out the first comparative mitogenomic study in oligochaetes. The mitogenomes of 15 earthworm species were sequenced and compared with other 9 available earthworm mitogenomes, with the main aim to explore their phylogenetic relationships and test different analytical approaches on phylogeny reconstruction. The general earthworm mitogenomic features revealed to be conservative: all genes encoded on the same strand, all the protein coding loci shared the same initiation codon (ATG) and tRNA genes showed conserved structures. The Drawida japonica mitogenome displayed the highest A + T content, reversed AT/GC-skews and the highest genetic diversity. Genetic distances among protein coding genes displayed their maximum and minimum interspecific values in the ATP8 and CO1 genes, respectively. The 22 tRNAs showed variable substitution patterns between the considered earthworm mitogenomes. The inclusion of rRNAs positively increased phylogenetic support. Furthermore, we tested different trimming tools for alignment improvement. Our analyses rejected reciprocal monophyly among Amynthas and Metaphire and indicated that the two genera should be systematically classified into one.

The subclass Acari (mites and ticks) comprises two super-orders: Acariformes and Parasitiformes. Most species of the Parasitiformes known retained the ancestral pattern of mitochondrial (mt) gene arrangement of arthropods and their mt tRNAs have the typical cloverleaf structure. All of the species of the Acariformes known, however, have rearranged mt genomes and truncated mt tRNAs. We sequenced the mt genomes of two species of Eriophyoidea: Phyllocoptes taishanensis and Epitrimerus sabinae. The mt genomes of P. taishanensis and E. sabinae are 13,475 bp and 13,531 bp, respectively, are circular and contain the 37 genes typical of animals; most mt tRNAs are highly truncated in both mites. On the other hand, these two eriophyoid mites have the least rearranged mt genomes seen in the Acariformes. Comparison between eriophyoid mites and other Aacariformes mites showed that: 1) the most recent common ancestor of Acariformes mites retained the ancestral pattern of mt gene arrangement of arthropods with slight modifications; 2) truncation of tRNAs for cysteine, phenylalanine and histidine occurred once in the most recent common ancestor of Acariformes mites whereas truncation of other tRNAs occurred multiple times; and 3) the placement of eriophyoid mites in the order Trombidiformes needs to be reviewed.

The helicene is constructed by twisted benzene or other aromatic rings, exhibiting a helical structure. Using first-principles calculations, we investigate the electronic transport of helicenes under stretching or compressing. Interestingly, a U-shaped curve of the current against d (the pitch of a helicene) is observed. Further analysis shows that, it is the result of the nonmonotonic change of HOMO-LUMO gap with d. The change of overlap between orbitals induced by conformational deformation is found to be the underlying mechanism. Moreover, the U-curve phenomenon is an intrinsic feature of the helicene molecules, being robust to the electrode materials or doping. This U-curve behavior is expected to be extended to helical graphene or other related structures, showing great application potential.

Leber’s hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.

Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD

Rhizosphere processes stimulate overyielding and facilitative phosphorus (P) uptake in cereal/legume intercropping systems. However, little is known about when and how rhizosphere alteration of legumes plays a role in improving P uptake by cereals. Wheat was grown isolated, monocropped or intercropped with faba bean in pots with low-P soil. The biomass, P content, carboxylates and phosphatases activity were measured in 15 destructive samplings. Intraspecific competition of the biomass and P uptake of monocropped wheat was not significant before 40 and 36 days after sowing (DAS), whereas there was interspecific competition of biomass of intercropped wheat before 66 DAS. However, afterwards, the increments of the biomass and P uptake of the intercropped wheat were 1.3–1.9 and 1.9–2.3 times of increment of monocropped wheat. Meanwhile, the concentrations of malate and citrate and the acid phosphatase activity in the rhizospheres of intercropped wheat were significantly increased, which suggested that wheat/faba bean intercropping is efficient in P utilization due to complementary P uptake in the early growth stage and the positive interactions of the rhizosphere processes when the soil P was depleted.

The mechanistic understanding of the dynamic processes linking nutrient acquisition and biomass production of competing individuals can be instructive in optimizing intercropping systems. Here, we examine the effect of inoculation with Funneliformis mosseae on competitive dynamics between wheat and faba bean. Wheat is less responsive to mycorrhizal inoculation. Both inoculated and uninoculated wheat attained the maximum instantaneous N and P capture approximately five days before it attained the maximum instantaneous biomass production, indicating that wheat detected the competitor and responded physiologically to resource limitation prior to the biomass response. By contrast, the instantaneous N and P capture by uninoculated faba bean remained low throughout the growth period, and plant growth was not significantly affected by competing wheat. However, inoculation substantially enhanced biomass production and N and P acquisition of faba bean. The exudation of citrate and malate acids and acid phosphatase activity were greater in mycorrhizal than in uninoculated faba bean, and rhizosphere pH tended to decrease. We conclude that under N and P limiting conditions, temporal separation of N and P acquisition by competing plant species and enhancement of complementary resource use in the presence of AMF might be attributable to the competitive co-existence of faba bean and wheat.

In our previous study, we had identified SOX30 as a novel tumor suppressor that acts through direct regulation of p53 transcription in human lung cancer. Here, we sought to determine the clinical relevance of SOX30 expression in a series of surgically-resected non-small cell lung cancer (NSCLC) patients. Analysis of SOX30 expression and clinico-pathologic features reveal a significant correlation of SOX30 expression with histological type (n = 220, P = 0.008) and clinical stage (n = 220, P = 0.024). Kaplan-Meier analysis indicates an association of high SOX30 expression with better prognosis in NSCLC patients (n = 220, P = 0.007). Via multivariate Cox-regression analysis, SOX30 expression is revealed to be an independent prognostic factor for overall survival (OS) of NSCLC patients (n = 220, P = 0.014, hazard ratio (HR) = 0.816). In particular, SOX30 is a favorable and independent prognostic factor in one main subtype of NSCLC, lung adenocarcinoma (ADC) patients (n = 150, P = 0.000, HR = 0.405), but not in another main subtype of NSCLC, squamous cell carcinoma patients. Furthermore, high expression of SOX30 represents a favorable and independent factor for the prognosis of ADC patients at clinical stage II (P = 0.013), with positive lymph node (P = 0.003), at histological grade 2 (P = 0.000) or grade 3 (P = 0.025). In summary, SOX30 expression represents an important prognostic factor for survival time in ADC patients.

Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 ± 0.3 μM, which was smaller than that of (−)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aβ42 monomers and its mature fibrils into unstructured Aβ aggregates with some β-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aβ42 fibrillogenesis by directly binding to Aβ42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.