Search

Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

Protein (un)folding is a complex and essential process. With the rapid development of single-molecule techniques, we can detect multiple and transient proteins (un)folding pathways/intermediates. However, the observation of multiple multistep (>2) unfolding scenarios for a single protein domain remains limited. Here, we chose metalloprotein with relatively stable and multiple metal-ligand coordination bonds as a system for such a purpose. Using AFM-based single-molecule force spectroscopy (SMFS), we successfully demonstrated the complex and multistep protein unfolding scenarios of the β-domain of a human protein metallothionein-3 (MT). MT is a protein of ~60 amino acids (aa) in length with 20 cysteines for various metal binding, and the β-domain (βMT) is of ~30 aa with an M3S9 metal cluster. We detected four different types of three-step protein unfolding scenarios from the Cd-βMT, which can be possibly explained by the rupture of Cd-S bonds in the complex Cd3S9 metal cluster. In addition, complex unfolding scenarios with four rupture peaks were observed. The Cd-S bonds ruptured in both single bond and multiple bonds modes. Our results provide not only evidence for multistep protein unfolding phenomena but also reveal unique properties of metalloprotein system using single-molecule AFM.

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel–Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73–0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13–1.48, P P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. 131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. 90Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47–6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20+ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, 90Y-ibritumomab tiuxetan increases ORR.

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel–Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73–0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13–1.48, P

Normalized difference vegetation index (NDVI) is one of the most important vegetation indices in crop remote sensing. It features a simple, fast, and non-destructive method and has been widely used in remote monitoring of crop growing status. Beer-Lambert law is widely used in calculating crop leaf area index (LAI), however, it is time-consuming detection and low in output. Our objective was to improve the accuracy of monitoring LAI through remote sensing by integrating NDVI and Beer-Lambert law. In this study, the Beer-Lambert law was firstly modified to construct a monitoring model with NDVI as the independent variable. Secondly, experimental data of wheat from different years and various plant types (erectophile, planophile and middle types) was used to validate the modified model. The results showed that at 130 DAS (days after sowing), the differences in NDVI, leaf area index (LAI) and extinction coefficient (k) of the three plant types with significantly different leaf orientation values (LOVs) reached the maximum. The NDVI of the planophile-type wheat reached saturation earlier than that of the middle and erectophile types. The undetermined parameters of the model (LAI = −ln (a1 × NDVI + b1)/(a2 × NDVI + b2)) were related to the plant type of wheat. For the erectophile-type cultivars (LOV ≥ 60°), the parameters for the modified model were, a1 = 0.306, a2 = −0.534, b1 = −0.065, and b2 = 0.541. For the middle-type cultivars (30° 1 = 0.392, a2 = −0.881, b1 = 0.028, and b2 = 0.845. And for the planophile-type cultivars (LOV ≤ 30°), those parameters were, a1 = 0.596, a2 = −1.306, b1 = 0.014, and b2 = 1.130. Verification proved that the modified model based on integrating NDVI and Beer-Lambert law was better than Beer-Lambert law model only or NDVI-LAI direct model only. It was feasible to quantitatively monitor the LAI of different plant-type wheat by integrating NDVI and Beer-Lambert law, especially for erectophile-type wheat (R2 = 0.905, RMSE = 0.36, RE = 0.10). The monitoring model proposed in this study can accurately reflect the dynamic changes of plant canopy structure parameters, and provides a novel method for determining plant LAI.

Aluminum alloy in situ functionally graded materials (FGMs) have been successfully fabricated using directional solidification under an axial static magnetic field. Al-Zn, Al-Ni and Al-Cu alloys with a hypereutectic composition were selected to produce FGMs. Experimental results show that the graded composition of the primary phases (i.e., Zn, Al3Ni and Al2Cu) is obvious along the longitudinal section of the sample. The graded composition of the primary phases could be controlled by the value of the magnetic field, growth rate and temperature gradient. A proposed model and simulations are carried out to explain the origin of the graded composition of the primary phases in FGMs during directional solidification under an axial static magnetic field. It should be attributed to the combined actions of heavier species migration under gravity force and thermoelectric (TE) magnetic convection under magnetic field. Furthermore, it can be found that the magnetic field can induce the columnar FGMs to change into equiaxed FGMs. This work not only presents a new approach to fabricate FGMs using the directional solidification under an axial static magnetic field but also deeply understands the effect of the solute migration and temperature distribution on the crystal growth during directional solidification.

This study evaluated cutaneous microbial distribution, and microbial co-occurrence at different body sites and skin environments in Chinese women (39.6 ± 11.9 years, N = 100) during the winter season. Microbial distribution (Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus, Pseudomonadaceae, and Malassezia furfur), association with biomarkers (antimicrobial peptides: LL-37, β-defensins [HBD-2, HBD-3]), and claudin-1) and skin biophysical parameters (transepidermal water loss, pH, skin scaliness and roughness, sebum and hydration levels) were also determined. Skin sites (glabella [GL], hand-back [HB], interdigital web-space [IS], antecubital fossa [AF], volar forearm [VF], back [BA]) were classified as normal, oily or dry based on two-step cluster analysis and exposed or unexposed (uncovered or covered by clothes, respectively) based on seasonal apparel. Pseudomonadaceae and Staphylococcus aureus had the highest and lowest detection rate respectively at all sites. Cluster analysis identified skin sites as ‘normal’ (HB, BA, AF, VF), ‘dry’ (IS) and ‘oily’ (GL). Bacterial alpha diversity was higher in exposed (HB, IS, and GL) compared with unexposed sites (BA, AF and VF). Co-occurrence of Staphylococcus aureus with any of the other five microorganisms was lower in dry and oily skin versus normal skin. Skin exposure, biophysical/barrier profile and biomarkers were found to be associated with bacterial distribution and co-occurrence.

For applying an alternating magnetic field (AMF) in materials processing it is of high significance to understand the physical mechanisms behind the change in diffusivity in the AMF. In this work, the effect of the AMF on interdiffusion in a Ni-Cr alloy was investigated with a diffusion couple. The interdiffusion coefficient was found to increase with increasing AMF intensity. The faster diffusivity is a consequence of the enhancement of the dislocation density in the diffusion couples that was confirmed by the broadening of X-ray diffraction peaks. The higher dislocation density is attributed to the magnetoplastic effect (MPE). Theoretical considerations on the relation of MPE, dislocation density and diffusivity are in agreement with the experimental results.

Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.

Species from the genus Talaromyces produce useful biomass-degrading enzymes and secondary metabolites. However, these enzymes and secondary metabolites are still poorly understood and have not been explored in depth because of a lack of comprehensive genetic information. Here, we report a 36.51-megabase genome assembly of Talaromyces pinophilus strain 1–95, with coverage of nine scaffolds of eight chromosomes with telomeric repeats at their ends and circular mitochondrial DNA. In total, 13,472 protein-coding genes were predicted. Of these, 803 were annotated to encode enzymes that act on carbohydrates, including 39 cellulose-degrading and 24 starch-degrading enzymes. In addition, 68 secondary metabolism gene clusters were identified, mainly including T1 polyketide synthase genes and nonribosomal peptide synthase genes. Comparative genomic analyses revealed that T. pinophilus 1–95 harbors more biomass-degrading enzymes and secondary metabolites than other related filamentous fungi. The prediction of the T. pinophilus 1–95 secretome indicated that approximately 50% of the biomass-degrading enzymes are secreted into the extracellular environment. These results expanded our genetic knowledge of the biomass-degrading enzyme system of T. pinophilus and its biosynthesis of secondary metabolites, facilitating the cultivation of T. pinophilus for high production of useful products.

Remote sensing has been used as an important means of estimating crop production, especially for the estimation of crop yield in the middle and late growth period. In order to further improve the accuracy of estimating winter wheat yield through remote sensing, this study analyzed the quantitative relationship between satellite remote sensing variables obtained from HJ-CCD images and the winter wheat yield, and used the partial least square (PLS) algorithm to construct and validate the multivariate remote sensing models of estimating the yield. The research showed a close relationship between yield and most remote sensing variables. Significant multiple correlations were also recorded between most remote sensing variables. The optimal principal components numbers of PLS models used to estimate yield were 4. Green normalized difference vegetation index (GNDVI), optimized soil-adjusted vegetation index (OSAVI), normalized difference vegetation index (NDVI) and plant senescence reflectance index (PSRI) were sensitive variables for yield remote sensing estimation. Through model development and model validation evaluation, the yield estimation model’s coefficients of determination (R2) were 0.81 and 0.74 respectively. The root mean square error (RMSE) were 693.9 kg ha−1 and 786.5 kg ha−1. It showed that the PLS algorithm model estimates the yield better than the linear regression (LR) and principal components analysis (PCA) algorithms. The estimation accuracy was improved by more than 20% than the LR algorithm, and was 13% higher than the PCA algorithm. The results could provide an effective way to improve the estimation accuracy of winter wheat yield by remote sensing, and was conducive to large-area application and promotion.

Protein (un)folding is a complex and essential process. With the rapid development of single-molecule techniques, we can detect multiple and transient proteins (un)folding pathways/intermediates. However, the observation of multiple multistep (>2) unfolding scenarios for a single protein domain remains limited. Here, we chose metalloprotein with relatively stable and multiple metal-ligand coordination bonds as a system for such a purpose. Using AFM-based single-molecule force spectroscopy (SMFS), we successfully demonstrated the complex and multistep protein unfolding scenarios of the β-domain of a human protein metallothionein-3 (MT). MT is a protein of ~60 amino acids (aa) in length with 20 cysteines for various metal binding, and the β-domain (βMT) is of ~30 aa with an M3S9 metal cluster. We detected four different types of three-step protein unfolding scenarios from the Cd-βMT, which can be possibly explained by the rupture of Cd-S bonds in the complex Cd3S9 metal cluster. In addition, complex unfolding scenarios with four rupture peaks were observed. The Cd-S bonds ruptured in both single bond and multiple bonds modes. Our results provide not only evidence for multistep protein unfolding phenomena but also reveal unique properties of metalloprotein system using single-molecule AFM.

α-Synuclein is a protein that aggregates as amyloid fibrils in the brains of patients with Parkinson’s disease and dementia with Lewy bodies. Small oligomers of α-synuclein are neurotoxic and are thought to be closely associated with disease. Whereas α-synuclein fibrillization and fibril morphologies have been studied extensively with various methods, the earliest stages of aggregation and the properties of oligomeric intermediates are less well understood because few methods are able to detect and characterize early-stage aggregates. We used fluorescence spectroscopy to investigate the early stages of aggregation by studying pairwise interactions between α-synuclein monomers, as well as between engineered tandem oligomers of various sizes (dimers, tetramers, and octamers). The hydrodynamic radii of these engineered α-synuclein species were first determined by fluorescence correlation spectroscopy and dynamic light scattering. The rate of pairwise aggregation between different species was then monitored using dual-color fluorescence cross-correlation spectroscopy, measuring the extent of association between species labelled with different dyes at various time points during the early aggregation process. The aggregation rate and extent increased with tandem oligomer size. Self-association of the tandem oligomers was found to be the preferred pathway to form larger aggregates: interactions between oligomers occurred faster and to a greater extent than interactions between oligomers and monomers, indicating that the oligomers were not as efficient in seeding further aggregation by addition of monomers. These results suggest that oligomer-oligomer interactions may play an important role in driving aggregation during its early stages.

Peritectic alloy Cu-10.5 at.% Sn was directionally solidified at various growth speeds under a transverse static magnetic field. The experimental results indicated that the magnetic field caused the deformation of macroscopic interface morphology, the crystal orientation of primary phase along solidification direction, and the occurrence of peritectic reaction. The numerical simulations showed that the application of the magnetic field induced the formation of a unidirectional thermoelectric magnetic convection (TEMC), which modified solute transport in the liquid phase thereby enriching the solute concentration both at the sample and tri-junction scales. The modification of solidification structures under the magnetic field should be attributed to TEMC driven heat transfer and solute transport.

Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson’s disease and other neurodegenerative disorders. However, small oligomers are difficult to isolate for study. To gain better insight into the properties of small α-synuclein oligomers, we investigated engineered oligomers of specific size (dimers, tetramers, and octamers) linked head-to-tail in tandem, comparing the behavior of the oligomers to monomeric α-synuclein. All oligomeric constructs remained largely disordered in solution, as determined from dynamic light scattering and size-exclusion chromatography. Electron microscopy revealed that each construct could aggregate to form fibrils similar to those formed by monomeric α-synuclein. The interactions with large unilamellar vesicles (LUVs) composed of negatively-charged lipids differed depending on size, with smaller oligomers forming more extensive helical structure as determined by CD spectroscopy. Monitoring the influx of a fluorescence bleaching agent into vesicles showed that larger oligomers were somewhat more effective at degrading vesicular integrity and inducing membrane permeabilization.

Bitter taste receptors (TAS2Rs) have attracted a great deal of interest because of their recently described bronchodilator and anti-inflammatory properties. The aim of this study was to identify natural direct TAS2R14 agonists from Radix Bupleuri that can inhibit mast cell degranulation. A ligand-based virtual screening was conducted on a library of chemicals contained in compositions of Radix Bupleuri, and these analyses were followed by cell-based functional validation through a HEK293-TAS2R14-G16gust44 cell line and IgE-induced mast cell degranulation assays, respectively. Saikosaponin b (SSb) was confirmed for the first time to be a specific agonist of TAS2R14 and had an EC50 value of 4.9 μM. A molecular docking study showed that SSb could directly bind to a TAS2R14 model through H-bond interactions with Arg160, Ser170 and Glu259. Moreover, SSb showed the ability to inhibit IgE-induced mast cell degranulation, as measured with a β-hexosaminidase release model and real-time cell analysis (RTCA). In a cytotoxicity bioassay, SSb showed no significant cytotoxicity to HEK293 cells within 24 hours. This study demonstrated that SSb is a direct TAS2R14 agonist that inhibit IgE-induced mast cell degranulation. Although the target and in vitro bioactivity of SSb were revealed in this study, it still need in vivo study to further verify the anti-asthma activity of SSb.

MicroRNA (miR)-132 has been identified as a top up-regulated miRNA during skin wound healing and its inhibition impairs wound repair. In a human in vivo surgical wound model, we showed that miR-132 was induced in epidermal as well as in dermal wound–edge compartments during healing. Moreover, in a panel of cells isolated from human skin wounds, miR-132 was found highly expressed in human dermal fibroblasts (HDFs). In HDFs, miR-132 expression was upregulated by TGF-β1. By overexpression or inhibition of miR-132, we showed that miR-132 promoted HDF migration. Mechanistically, global transcriptome analysis revealed that RAS signaling pathway was regulated by miR-132 in HDFs. We found that RAS p21 protein activator 1 (RASA1), a known target of miR-132, was downregulated in HDFs upon miR-132 overexpression. Silencing of RASA1 phenocopied the pro-migratory effect of miR-132. Collectively, our study reveals an important role for miR-132 in HDFs during wound healing and indicates a therapeutic potential of miR-132 in hard-to-heal skin wounds.

Studies of the molecular mechanisms involved in the formation of the albino leaf cells are important for understanding the development of chimera leaves in Ananas comosus var. bracteatus. In this study, we identified a total of 163 novel miRNAs involved in the development of complete white (CWh) and complete green (CGr) leaves using high-throughput sequencing method. The potential miRNA target genes were predicted and annotated using the NR, Swiss-Prot, GO, COG, KEGG, KOG and Pfam databases. The main biological processes regulated by miRNAs were revealed. The miRNAs which potentially play important roles in the development of the leaves and the albino of the CWh leaf cells were selected and their expression patterns were analyzed. The expression levels of nine miRNAs and their potential target genes were studied using qRT-PCR. These results will help to elucidate the functional and regulatory roles of miRNAs in the formation of the albino cells and the development of the leaves of A. comosus var. bracteatus. These data may also be helpful as a resource for studies of small RNA in other leaf color chimeric plant species.

Highly-monodispersed g-C3N4/TiO2 hybrids with a core/shell structure were synthesized from a simple room temperature impregnation method, in which g-C3N4 was coated through self-assembly on the commercially available Degussa P25 TiO2 nanoparticles. Structural and surface characterizations showed that the presence of g-C3N4 notably affected the light absorption characteristics of TiO2. The g-C3N4/TiO2 heterojunctions with metal-free exposed surfaces were directly used as biocompatible photocatalysts for simulated jaundice phototherapy under low-power green-light irradiation. The photocatalytic activity and stability of g-C3N4/TiO2 were enhanced relative to pure P25 or g-C3N4, which could be ascribed to the effective Z-scheme separation of photo-induced charge carriers in g-C3N4/TiO2 heterojunction. The photoactivity was maximized in the 4 wt.% g-C3N4-coated P25, as the bilirubin removal rate under green light irradiation was more than 5-fold higher than that under the clinically-used blue light without any photocatalyst. This study approves the future applications of the photocatalyst-assisted bilirubin removal in jaundice treatment under moderate green light which is more tolerable by humans.

Wolbachia pipientis are intracellular endosymbionts that induce parthenogenesis in the parasitoid Encarsia formosa. Previous studies that focused on effects of Wolbachia on the wasp usually used tetracycline to remove Wolbachia without concern for the joint influences of tetracycline and Wolbachia. Here we treated the wasps (F0 lines) with tetracycline to produce offspring (F1 lines) which were not fed tetracycline to avoid antibiotic influence. The quantitative data and fluorescence in situ hybridization showed that Wolbachia titers were reduced but not totally removed. The Wolbachia that infected the male offspring were unpredictably detected. Low dose tetracycline enhanced the fertility of 2-day-old F0 wasps after 24 h of treatment; however, compared with controls, the oocyte load of 3- to 6-day-old tetracycline-treated wasps decreased day by day, and tetracycline reduced the longevity of the wasps. The fecundity of controls was significantly higher than that of the treated F1-10 and F1-20 generations. Gene expression of vitellogenin reflected the same trend as that of wasp fecundities in both F0 and F1 lines. Moreover, female offspring proportions of F0 and F1 lines were related to the titer of infected Wolbachia, demonstrating that Wolbachia titer affected the sex determination of E. formosa.

Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.

Animal mitochondrial genomes usually exhibit conserved gene arrangement across major lineages, while those in the Hymenoptera are known to possess frequent rearrangements, as are those of several other orders of insects. Here, we sequenced two complete mitochondrial genomes of Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae). In total, 37 mitochondrial genes were identified in both species. The same gene arrangement pattern was found in the two species, with extensive gene rearrangement compared with the ancestral insect mitochondrial genome. Most tRNA genes and all protein-coding genes were encoded on the minority strand. In total, 15 tRNA genes and seven protein-coding genes were rearranged. The rearrangements of cox1 and nad2 as well as most tRNA genes were novel. Phylogenetic analysis based on nucleotide sequences of protein-coding genes and on gene arrangement patterns produced identical topologies that support the relationship of (Agaonidae + Pteromalidae) + Trichogrammatidae in Chalcidoidea. CREx analysis revealed eight rearrangement operations occurred from presumed ancestral gene order of Chalcidoidea to form the derived gene order of Trichogramma. Our study shows that gene rearrangement information in Chalcidoidea can potentially contribute to the phylogeny of Chalcidoidea when more mitochondrial genome sequences are available.

Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11.7 months. Cox analysis showed that PS 0–1, recurrent disease, EGFR mutations, or EGFR-TKI treatment were associated with improved OS. In patients with EGFR-activating mutations, Cox analysis showed that patients with adenocarcinoma, recurrent disease, or EGFR-TKI treatment had significantly longer survival. Patients with EGFR-activating mutations who received EGFR-TKI therapy had a median OS of 24.3 months, which was significantly longer than those who had not received EGFR-TKI therapy (10.8 months). Patients with wild-type EGFR had a median OS of 9.7 months and Cox analysis showed that PS score and disease type were independent predictors. EGFR-TKI therapy is an independently prognostic factor for NSCLC with mutated EGFR. A more effective therapy is needed for patients with wild-type EGFR.

The wMel Wolbachia strain was known for cytoplasmic incompatibility (CI)-induction and blocking the transmission of dengue. However, it is unknown whether it can establish and induce CI in a non-dipteran host insect. Here we artificially transferred wMel from Drosophila melanogaster into the whitefly Bemisia tabaci. Fluorescence in situ hybridisation demonstrated that wMel had successfully transfected the new host. Reciprocal crossing was conducted with wMel-transfected and wild-type isofemale lines, indicating that wMel could induce a strong CI without imposing significant cost on host fecundity. We then determined the maternal transmission efficiency of wMel in the offspring generations, showing a fluctuating trend over a period of 12 generations. We thus detected the titre of wMel during different developmental stages and in different generations by using real-time quantitative PCR, revealing a similar fluctuating mode, but it was not significantly correlated with the dynamics of transmission efficiency. These results suggest that wMel can be established in B.tabaci, a distantly related pest insect of agricultural importance; moreover, it can induce a strong CI phenotype in the recipient host insect, suggesting a potential for its use in biological control of B. tabaci.