A Cascade Activation Probe with Double-Enhanced Near-Infrared Imaging for Monitoring Peroxynitrite Fluctuations in Vivo.

Monitoring peroxynitrite (ONOO-) fluctuations is particularly important for assessing pathological progression and oxidative damage due to their crucial role in maintaining the redox balance of organisms. However, due to the lack of efficient tools for differentially monitoring ONOO- fluctuations at different concentration ranges in vivo, the precise detection of endogenous ONOO- fluctuations under pathological conditions in living systems remains challenging. Herein, we rationally designed a double-enhanced emission cascade activatable near-infrared (NIR) fluorescent probe (B-TCF) for the measurement of ONOO-, which consists of a borate ester response group and a malononitrile hemicyanine fluorophore. Especially, after sequential oxidative hydrolysis of the borate ester group and xanthene skeleton, B-TCF exhibited a sequentially double-enhanced NIR emission response at 776 and 625 nm for different ONOO- concentration ranges. Moreover, B-TCF revealed excellent and promising performance for ONOO- in terms of high selectivity, sensitivity, and reaction rate (k = 28.2 M-1 s-1). Motivated by the two-step emission signal enhancement and large wavelength shift in the NIR region, B-TCF enabled discriminative imaging of ONOO- with the low and high concentrations in living cells. Importantly, B-TCF was successfully applied for assessing the pathological progression of isoniazid and acetaminophen-induced liver damage in vivo by detecting the endogenous different ONOO- levels. Overall, this study not only demonstrates the first double-enhanced emission cascade activatable NIR fluorescent probe for measuring the dynamic variation of ONOO- in related diseases but also shows great potential as an effective molecular tool for evaluating the various stages of drug-induced liver damage.

Genome sequence of the progenitor of wheat A subgenome Triticum urartu.

Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat1,2. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing 3 , linked reads and optical mapping4,5. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.

Exploring the relationships between hormone receptor, HER2 status, and bone involvement in the first distant metastases of in Chinese breast cancer patients who lacked HER2 targeted therapy.

BACKGROUND: This retrospective study explored the relationship between hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) status, and bone involvement in the first distant metastases (DM) of Chinese breast cancer (BC) patients who lacked the HER2 targeted therapy. Such therapy was rarely received due to its lag approval or high cost in China compared with the developed countries. METHODS: All eligible women with primary unilateral stage I - III BC and first DM diagnosed in 2008-2018 at one cancer center were identified for enrollment. Based on chart records, a full or no/partial compliance status of endocrine therapy (ET) was assigned for HR-positive patients. Multivariate logistic regression was used to estimate the adjusted odd ratio (aOR), its 95%CI and p value. RESULTS: Four hundred eighteen patients had an average age of 50.7 years and median disease-free survival of 27.1 months at DM. Bone, lung, liver and brain metastasis rates in patients were 55.7%, 34.7%, 33.0% and 8.1%, respectively. Compared to HR-negative patients, HR-positive patients with the full and non/partial compliance of ET were significantly associated with higher risk of bone involvement with an aOR of 2.329 (1.316 - 1.741, p = 0.004) and 2.317 (1.330 - 4.036, p = 0.003), respectively. No difference of such risk was found between the two groups of ET compliance (p = 0.984) nor between HER2-negative and HER2-positive patients (aOR 0.827, p = 0.431). Stratified analyses further indicated that HR-positive was associated with bone involvement only in HER2-negative BC patients (p = 0.006-0.015). CONCLUSIONS: HR-positive tumors are significantly associated with bone involvement in HER2-negative metastatic BC patients. ET does not appear to impact this association. HER2 status per se is not associated with such risk.

Identification and introgression of a novel leaf rust resistance gene from Thinopyrum intermedium chromosome 7Js into wheat.

KEY MESSAGE: A novel leaf rust resistance locus located on a terminal segment (0-69.29 Mb) of Thinopyrum intermedium chromosome arm 7JsS has been introduced into wheat genome for disease resistance breeding. Xiaoyan 78829, a wheat-Thinopyrum intermedium partial amphiploid, exhibits excellent resistance to fungal diseases in wheat. To transfer its disease resistance to common wheat (Triticum aestivum), we previously developed a translocation line WTT26 using chromosome engineering. Disease evaluation showed that WTT26 was nearly immune to 14 common races of leaf rust pathogen (Puccinia triticina) and highly resistant to Ug99 race PTKST of stem rust pathogen (P. graminis f. sp. tritici) at the seedling stage. It also displayed high adult plant resistance to powdery mildew (caused by Blumeria graminis f. sp. tritici). Cytogenetic and molecular marker analysis revealed that WTT26 carried a T4BS·7JsS chromosome translocation. Once transferred into the susceptible wheat genetic background, chromosome 7JsS exhibited its resistance to leaf rust, indicating that the resistance locus was located on this alien chromosome. To enhance the usefulness of this locus in wheat breeding, we further developed several new translocation lines with small Th. intermedium segments using irradiation and developed 124 specific markers using specific-locus amplified fragment sequencing, which increased the marker density of chromosome 7JsS. Furthermore, a refined physical map of chromosome 7JsS was constructed with 74 specific markers, and six bins were thus arranged according to the co-occurrence of markers and alien chromosome segments. Combining data from specific marker amplification and resistance evaluation, we mapped a new leaf rust resistance locus in the 0-69.29 Mb region on chromosome 7JsS. The translocation lines carrying the new leaf rust resistance locus and its linked markers will contribute to wheat disease-resistance breeding.

Psychometric properties of the post-traumatic stress disorder checklist for DSM-5 (PCL-5) in Chinese stroke patients.

BACKGROUND: Stroke is a devastating disease and can be sufficiently traumatic to induce post-traumatic stress disorder (PTSD). Post-stroke PTSD is attracting increasing attention, but there was no study assessing the psychometric properties of the PCL-5 in stroke populations. Our study was conducted to examine the psychometric properties of the PTSD Checklist for DSM-5 (PCL-5) in Chinese stroke patients. METHODS: This was a cross-sectional observational study conducted at our hospital. Three hundred and forty-eight Chinese stroke patients came to our hospital for outpatient service were recruited. They were instructed to complete the PCL-5 scales and were interviewed for PTSD diagnosis with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). The cutoff scores, reliability and validity of the PCL-5 were analyzed. RESULTS: PCL-5 scores in our sample were positively skewed, suggesting low levels of PTSD symptoms. The reliability of PCL-5 was good. Exploratory and confirmatory factor analyses indicated acceptable construct validity, and confirmed the multi-dimensionality of the PCL-5. By CFA analysis, the seven-factor hybrid model demonstrated the best model fit. The PCL-5 also showed good convergent validity and discriminant validity. Receiver operating characteristic (ROC) analyses revealed a PCL-5 score of 37 achieved optimal sensitivity and specificity for detecting PTSD. CONCLUSIONS: Our findings supported the use of PCL-5 as a psychometrically adequate measure of post-stroke PTSD in the Chinese patients.

A large single-center prospective study to investigate the factors influencing the choice of breast-conserving surgery versus mastectomy in Chinese women with early breast cancer.

BACKGROUND: Compared to mastectomy, breast-conserving surgery (BCS) provides the same survival rate and a higher quality of life for patients with early breast cancer (EBC). However, Chinese women with EBC are known to have a low BCS rate. A large prospective cohort study was conducted to investigate the factors influencing the choice of BCS in this population. METHODS: In 2017, all women with unilateral EBC and eligible for BCS at our institution were enrolled. Before surgery, the patient's trust in the surgeon and her perceived strength of the surgeon's recommendation of BCS were measured through an in-person interview and validated ad hoc questionnaire. Multivariate logistic regressions on BCS procedure vs. mastectomy were used to estimate the odds ratio (OR). RESULTS: One thousand one hundred thirty-six patients enrolled at analysis had an average age of 51.8 and tumor size of 2.4 cm. 19.9% of patients had BCS. The "strong" level of trust in the surgeon was significantly associated with BCS with an OR of 2.944 (p<0.001) when compared to the "average or under" trust. The "strong" and "moderate" strengths in surgeon recommendation for BCS were also found to be significantly associated with the BCS procedure with ORs of 12.376 (p <0.001) and 1.757 (p =0.040), respectively, compared to the "neutral or dissuaded" strength. CONCLUSIONS: Stronger trust in surgeons and BCS recommendation by surgeons are associated with a higher rate of BCS in Chinese women with EBC. Interventional trials are needed to confirm this finding.

Cytogenetic identification and molecular marker development of a novel wheat-Thinopyrum ponticum translocation line with powdery mildew resistance.

KEY MESSAGE: A new wheat-Thinopyrum ponticum translocation line with excellent powdery mildew resistance was produced, and alien-specific PCR markers and FISH probes were developed by SLAF-seq. Powdery mildew is one of the most threatening diseases in wheat production. Thinopyrum ponticum (Podp.) Barkworth and D. R. Dewey, as a wild relative, has been used for wheat genetic improvement for the better part of a century. In view of the good powdery mildew resistance of Th. ponticum, we have been working to transfer the resistance genes from Th. ponticum to wheat by creating translocation lines. In this study, a new wheat-Th. ponticum translocation line with excellent resistance and agronomic performance was developed and through seedling disease evaluation, gene postulation and diagnostic marker analysis proved to carry a novel Pm gene derived from Th. ponticum. Cytogenetic analysis revealed that a small alien segment was translocated to the terminal of chromosome 1D to form new translocation TTh-1DS·1DL chromosome. The translocation breakpoint was determined to lie in 21.5 Mb region of chromosome 1D by using Wheat660K SNP array analysis. Based on specific-locus amplified fragment sequencing (SLAF-seq) technology, eight molecular markers and one repetitive sequence probe were developed, which were specific for Th. ponticum. Fortunately, the probe could be used in distinguishing six alien chromosome pairs in partial amphiploid Xiaoyan 7430 by fluorescence in situ hybridization (FISH). Furthermore, a Thinopyrum-specific oligonucleotide probe was designed depending on the sequence information of the FISH probe. The novel translocation line could be used in wheat disease resistance breeding, and these specific markers and probes will enable wheat breeders to rapidly trace the alien genome with the novel Pm gene(s).

Establishment and identification of six wheat-Thinopyrum ponticum disomic addition lines derived from partial amphiploid Xiaoyan 7430.

KEY MESSAGE: Six wheat-Thinopyrum ponticum disomic addition lines derived from partial amphiploid Xiaoyan 7430 were identified using in situ hybridization and SNP microarray, the homoeologous group and stripe rust resistance of each alien chromosome were determined, and Th. ponticum chromosome-specific markers were developed. Xiaoyan 7430 is a significant partial amphiploid, which is used to set up a bridge for transferring valuable genes from Thinopyrum ponticum (Podp.) Barkworth & D.R. Dewey into common wheat. To accelerate the application of these useful genes in enriching the genetic variability of cultivated wheat by chromosome engineering, a complete set of derived addition lines has been created from Xiaoyan 7430. The chromosome composition of each line was characterized by the combination of genomic in situ hybridization and multicolor fluorescence in situ hybridization (mc-FISH), and the homoeology of each alien chromosome was determined by wheat SNP microarray analysis. Addition line WTA55 with alien group-6 chromosome was evaluated resistant to stripe rust isolates at both the seedling and grain-filling stages (Zadoks scale at z.11 and z.73). Diagnostic marker analysis proved that it could carry a novel stripe rust resistance gene derived from Th. ponticum. Furthermore, a FISH probe and 45 molecular markers specific for alien chromosomes were developed based on specific-locus amplified fragment sequencing (SLAF-seq). Of which 27 markers were separately located on single alien chromosome, and some of them could be used to identify the derived translocation lines. This set of addition lines as well as the molecular markers and the FISH probe will promote the introgression of abundant variation from Th. ponticum into wheat in wheat improvement programs.

Genome-wide association study of yield and related traits in common wheat under salt-stress conditions.

BACKGROUND: Soil salinization is a major threat to wheat production. It is essential to understand the genetic basis of salt tolerance for breeding and selecting new salt-tolerant cultivars that have the potential to increase wheat yield. RESULT: In this study, a panel of 191 wheat accessions was subjected to genome wide association study (GWAS) to identify SNP markers linked with adult-stage characters. The population was genotyped by Wheat660K SNP array and eight phenotype traits were investigated under low and high salinity environments for three consecutive years. A total of 389 SNPs representing 11 QTLs were significantly associated with plant height, spike number, spike length, grain number, thousand kernels weight, yield and biological mass under different salt treatments, with the phenotypic explanation rate (R2) ranging from 9.14 to 50.45%. Of these, repetitive and pleiotropic loci on chromosomes 4A, 5A, 5B and 7A were significantly linked to yield and yield related traits such as thousand kernels weight, spike number, spike length, grain number and so on under low salinity conditions. Spike length-related loci were mainly located on chromosomes 1B, 3B, 5B and 7A under different salt treatments. Two loci on chromosome 4D and 5A were related with plant height in low and high salinity environment, respectively. Three salt-tolerant related loci were confirmed to be important in two bi-parental populations. Distribution of favorable haplotypes indicated that superior haplotypes of pleiotropic loci on group-5 chromosomes were strongly selected and had potential for increasing wheat salt tolerance. A total of 14 KASP markers were developed for nine loci associating with yield and related traits to improve the selection efficiency of wheat salt-tolerance breeding. CONCLUSION: Utilizing a Wheat660K SNPs chip, QTLs for yield and its related traits were detected under salt treatment in a natural wheat population. Important salt-tolerant related loci were validated in RIL and DH populations. This study provided reliable molecular markers that could be crucial for marker-assisted selection in wheat salt tolerance breeding programs.

Mapping QTL for agronomic traits under two levels of salt stress in a new constructed RIL wheat population.

KEY MESSAGE: QTL for 15 agronomic traits under two levels of salt stress in dry salinity field were mapped in a new constructed RIL population utilizing a Wheat55K SNP array. Furthermore, eight QTL were validated in a collected natural population. Soil salinity is one of the major abiotic stresses causing serious impact on crop growth, development and yield. As one of the three most important crops in the world, bread wheat (Triticum aestivum L.) is severely affected by salinity, too. In this study, an F7 recombinant inbred line (RIL) population derived from a cross between high-yield wheat cultivar Zhongmai 175 and salt-tolerant cultivar Xiaoyan 60 was constructed. The adult stage performances of the RIL population and their parent lines under low and high levels of salt stress were evaluated for three consecutive growing seasons. Utilizing a Wheat55K SNP array, a high-density genetic linkage map spinning 3250.71 cM was constructed. QTL mapping showed that 90 stable QTL for 15 traits were detected, and they were distributed on all wheat chromosomes except 4D, 6B and 7D. These QTL individually explained 2.34-32.43% of the phenotypic variation with LOD values ranging from 2.68 to 47.15. It was found that four QTL clusters were located on chromosomes 2D, 3D, 4B and 6A, respectively. Notably, eight QTL from the QTL clusters were validated in a collected natural population. Among them, QPh-4B was deduced to be an allele of Rht-B1. In addition, three kompetitive allele-specific PCR (KASP) markers derived from SNPs were successfully designed for three QTL clusters. This study provides an important base for salt-tolerant QTL (gene) cloning in wheat, and the markers, especially the KASP markers, will be useful for marker-assisted selection in salt-tolerant wheat breeding.

Chromosomal composition analysis and molecular marker development for the novel Ug99-resistant wheat-Thinopyrum ponticum translocation line WTT34.

KEY MESSAGE: A novel Ug99-resistant wheat-Thinopyrum ponticum translocation line was produced, its chromosomal composition was analyzed and specific markers were developed. Stem rust caused by Puccinia graminis f. sp. tritici Eriks. & E. Henn (Pgt) has seriously threatened global wheat production since Ug99 race TTKSK was first detected in Uganda in 1998. Thinopyrum ponticum is near immune to Ug99 races and may be useful for enhancing wheat disease resistance. Therefore, developing new wheat-Th. ponticum translocation lines that are resistant to Ug99 is crucial. In this study, a novel wheat-Th. ponticum translocation line, WTT34, was produced. Seedling and field evaluation revealed that WTT34 is resistant to Ug99 race PTKST. The resistance was derived from the alien parent Th. ponticum. Screening WTT34 with markers linked to Sr24, Sr25, Sr26, Sr43, and SrB resulted in the amplification of different DNA fragments from Th. ponticum, implying WTT34 carries at least one novel stem rust resistance gene. Genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization (mc-FISH), and multi-color GISH (mc-GISH) analyses indicated that WTT34 carries a T5DS·5DL-Th translocation, which was consistent with wheat660K single-nucleotide polymorphism (SNP) array results. The SNP array also uncovered a deletion event in the terminal region of chromosome 1D. Additionally, the homeology between alien segments and the wheat chromosomes 2A and 5D was confirmed. Furthermore, 51 PCR-based markers derived from the alien segments of WTT34 were developed based on specific-locus amplified fragment sequencing (SLAF-seq). These markers may enable wheat breeders to rapidly trace Th. ponticum chromosomal segments carrying Ug99 resistance gene(s).

Mapping QTL for seedling morphological and physiological traits under normal and salt treatments in a RIL wheat population.

KEY MESSAGE: The genetic basis of 27 seedling traits under normal and salt treatments was fully analyzed in a RIL wheat population, and seven QTL intervals were validated in two other genetic populations. Soil salinity seriously constrains wheat (Triticum aestivum L.) production globally by influencing its growth and development. To explore the genetic basis of salt tolerance in wheat, a recombinant inbred line (RIL) population derived from a cross between high-yield wheat cultivar Zhongmai 175 (ZM175) and salt-tolerant cultivar Xiaoyan 60 (XY60) was used to map QTL for seedling traits under normal and salt treatments based on a high-density genetic linkage map. A total of 158 stable additive QTL for 27 morphological and physiological traits were identified and distributed on all wheat chromosomes except 3A and 4D. They explained 2.35-46.43% of the phenotypic variation with a LOD score range of 2.61-40.38. The alleles from XY60 increased corresponding traits for 100 QTL, while the alleles from ZM175 had positive effects for the other 58 QTL. Nearly half of the QTL (78/158) were mapped in nine QTL clusters on chromosomes 2A, 2B, 2D, 4B, 5A, 5B, 5D, and 7D (2), respectively. To prove the reliability and potentiality in molecular marker-assisted selection (MAS), seven QTL intervals were validated in two other genetic populations. Besides additive QTL, 94 pairs of loci were detected with significant epistatic effect and 20 QTL were found to interact with treatment. This study provides a full elucidation of the genetic basis of seedling traits (especially root system-related traits) associated with salt tolerance in wheat, and the developed kompetitive allele-specific PCR markers closely linked to stable QTL would supply strong supports to MAS in salt-tolerant wheat breeding.

Structural brain assessment of temporal lobe epilepsy based on voxel-based and surface-based morphological features.

AIM OF THE STUDY: This study aimed to assess the cerebral voxel-based and surface-based morphological abnormalities of patients with temporal lobe epilepsy (TLE). MATERIALS AND METHODS: A total of 100 healthy adults and 73 patients with TLE were enrolled in this study, and their 3D T1-weighted MRI data were collected. Voxel-based morphology (VBM) and surface-based morphology (SBM) tools were used to compare the morphological differences between healthy adults and patients with TLE. Receiver-operating characteristic (ROC) curves were used to acquire the boundary values for detecting morphological abnormalities in regions of interest from the corrected VBM and SBM analysis. RESULTS: Our results showed that cortical voxels and decreased thickness areas were located in the widespread cortex and subcortical structures in the TLE group. However, after completing the analysis, we found that the left-TLE lesions were limited to the left temporal pole and left hippocampus, while the right-TLE lesions were located in the bilateral medial temporal lobe, including the right hippocampus and bilateral amygdala. ROC-curve results showed that the volume of the left hippocampus at 4,124.45 mm3 and the thickness of the left temporal pole cortex at 3.50 mm could be used as optimal boundary values based on the curves of the left-TLE group. The right-TLE group curves were poor. CONCLUSIONS: Widespread cerebral morphological TLE abnormalities were represented in this study. However, the lesions may be limited after completing a corrected comparison with clinical information. Boundary values of left-TLE group lesions were also obtained.

Plasticity in Triticeae centromere DNA sequences: a wheat × tall wheatgrass (decaploid) model.

Centromeres mediate chromosome attachment to microtubules and maintain the integrity of chromosomes for proper segregation of the sister chromatids during cell division. Advances in the assembly of Triticeae genome sequences combined with the capacity to recover hybrid species derived from very distantly related species provides potential experimental systems for linking retrotransposon amplification and repositioning of centromeres via non-mendelian inheritance in partial amphiploid breeds. The decaploid tall wheatgrass (Thinopyrum ponticum) is one of the most successfully used perennial species in wheat breeding for generating translocation lines with valuable agronomic traits. We found that wheat centromere retrotransposons CRW and Quinta widely occur within the tall wheatgrass genome. In addition, one of the genome donors to Th. ponticum, Pseudoroegneria stipifolia (StSt), has been shown to have Abigail and a satellite repeat, CentSt. We also found two other centromeric retrotransposons, Abia and CL135 in Th. ponticum by ChIP-seq. Examination of partial amphiploid lines that were generated in the 1970s demonstrated extensive modification in centromere sequences using CentSt, Abigail and Abia as probes. We also detected that St-genome chromosomes were more enriched with Abigail and CentSt, whereas E-genome chromosomes were enriched with CRW and Quinta in tall wheatgrass and its closer relatives. It can be concluded that bursts of transposition of retrotransposons and repositioning of centromeres via non-mendelian segregation are common in partial amphiploids derived from interspecific hybrids. Practically speaking, our study reveals that the existence of homologous centromere functional sequences in both a donor and its receptor can substantially contribute to the successful transfer of alien genes into crop species. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at https://www.ncbi.nlm.nih.gov/sra/SRR9089557; https://www.ncbi.nlm.nih.gov/sra/SRR9089558; https://www.ncbi.nlm.nih.gov/sra/SRR9089559; https://www.ncbi.nlm.nih.gov/sra/SRR9089560; https://www.ncbi.nlm.nih.gov/sra/SRR9089561; https://www.ncbi.nlm.nih.gov/sra/SRR9089562; https://www.ncbi.nlm.nih.gov/sra/SRR9089563; https://www.ncbi.nlm.nih.gov/sra/SRR9089564; https://www.ncbi.nlm.nih.gov/nuccore/MK999394; https://www.ncbi.nlm.nih.gov/nuccore/MK999395; https://www.ncbi.nlm.nih.gov/nuccore/MK999396.

Effects of major ozonated autoheamotherapy on functional recovery, ischemic brain tissue apoptosis and oxygen free radical damage in the rat model of cerebral ischemia.

Stroke is the second leading cause of death and disability in the world, with a heavy burden on patients, their families, and society. At present, a major focus of cerebrovascular disease research is to find a safe and effective new method to promote early functional recovery in the acute phase of cerebral infarction. Major ozonated autohemotherapy (MOAH) can maintain ATP and energy metabolism in cerebral ischemia and hypoxia, and reduce cell apoptosis. In the current study, the model of middle cerebral artery occlusion in the Sprague Dawley rat was established and evaluated by the clinical functional score, Hoechst staining, immunohistochemistry, Western blot analysis, and biochemical detection. Then, the effects of MOAH on neurological function, apoptosis, and oxygen free radical damage after acute ischemia in middle cerebral artery were evaluated. Moreover, the potential two mechanisms have been illustrated for MOAH effects. This study would lay a theoretical foundation for the application of MOAH and find an effective and early treatment method for the cerebral infarction.

Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases - a single-center retrospective analysis.

BACKGROUND: The relationship between whole brain radiotherapy (WBRT) dose with intracranial tumor control and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) brain metastases (BM) is largely unknown. METHODS: We retrospectively analyzed 595 NSCLC BM patients treated consecutively at the Fourth Hospital of Hebei Medical University between 2013 to 2015. We assigned the patients into 4 dose groups of WBRT: none, < 30, 30-39, and ≥ 40 Gy and assessed their relationship with OS and intracranial progression-free survival (iPFS). Cox models were utilized. Covariates included sex, age, KPS, BM lesions, extracranial metastasis, BM and lung tumor resection, chemotherapy, targeted therapy, and focal radiotherapy modalities. RESULTS: Patients had a mean age of 59 years and were 44% female. Their median survival time (MST) of OS and iPFS were 9.3 and 8.9 months. Patients receiving none (344/58%), < 30 (30/5%), 30-39 (93/16%), and ≥ 40 (128/22%) Gy of WBRT had MST of OS (iPFS) of 7.3 (6.8), 6.0 (5.4), 10.3 (11.9) and 11.9 (11.9) months, respectively. Compared to none, other WBRT groups had adjusted HRs for OS - 1.23 (p > 0.20), 0.72 (0.08), 0.61 (< 0.00) and iPFS - 1.63 (0.03), 0.71 (0.06), 0.67 (< 0.01). Compared to 30-39 Gy, WBRT dose ≥40 Gy was not associated with improved OS and iPFS (all p > 0.40). Stratified analyses by 1-3 and ≥ 4 BM lesions and adjustment analyses by each prognostic index of RPA class, Lung-GPA and Lung-molGPA supported these relationships as well. CONCLUSIONS: Compared to none, WBRT doses ≥30 Gy are invariably associated with improved intracranial tumor control and survival in NSCLC BM patients.

Draft genome of the wheat A-genome progenitor Triticum urartu.

Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.

Development of Thinopyrum ponticum-specific molecular markers and FISH probes based on SLAF-seq technology.

MAIN CONCLUSION: Based on SLAF-seq, 67 Thinopyrum ponticum-specific markers and eight Th. ponticum-specific FISH probes were developed, and these markers and probes could be used for detection of alien chromatin in a wheat background. Decaploid Thinopyrum ponticum (2n = 10x = 70) is a valuable gene reservoir for wheat improvement. Identification of Th. ponticum introgression would facilitate its transfer into diverse wheat genetic backgrounds and its practical utilization in wheat improvement. Based on specific-locus-amplified fragment sequencing (SLAF-seq) technology, 67 new Th. ponticum-specific molecular markers and eight Th. ponticum-specific fluorescence in situ hybridization (FISH) probes have been developed from a tiny wheat-Th. ponticum translocation line. These newly developed molecular markers allowed the detection of Th. ponticum DNA in a variety of materials specifically and steadily at high throughput. According to the hybridization signal pattern, the eight Th. ponticum-specific probes could be divided into two groups. The first group including five dispersed repetitive sequence probes could identify Th. ponticum chromatin more sensitively and accurately than genomic in situ hybridization (GISH). Whereas the second group having three tandem repetitive sequence probes enabled the discrimination of Th. ponticum chromosomes together with another clone pAs1 in wheat-Th. ponticum partial amphiploid Xiaoyan 68.

Physical mapping of the blue-grained gene from Thinopyrum ponticum chromosome 4Ag and development of blue-grain-related molecular markers and a FISH probe based on SLAF-seq technology.

KEY MESSAGE: A Thinopyrum ponticum chromosome 4Ag physical map was constructed, the blue-grained gene was localized, and related specific markers and a FISH probe were developed by SLAF-seq. Decaploid Thinopyrum ponticum (2n = 10x = 70) serves as an important gene pool for wheat improvement. The wheat-Th. ponticum 4Ag (4D) disomic substitution line Blue 58, derived from a distant hybridization between Th. ponticum and common wheat (Triticum aestivum L.), bears blue coloration in the aleurone layer. To map the blue-grained gene, eight wheat-Th. ponticum 4Ag translocation lines with different chromosomal segment sizes were obtained from Blue 58 using 60Co-γ ray irradiation and were characterized using cytogenetic and molecular marker analysis. A small-segment blue-grained wheat translocation line L13, accounting for one-fifth of 4AgL, was obtained. A physical map of chromosome 4Ag was constructed containing 573 specific-locus amplified fragment sequencing (SLAF-seq) markers, including three bins with 223 markers on 4AgS and eight bins with 350 markers on 4AgL. The blue-grained gene in three blue-grained translocation lines L5, L9, and L13, was located on bin 4AgL-6 with FL 0.75-0.89. Moreover, 89 blue-grain-related molecular markers and one fluorescence in situ hybridization (FISH) probe, pThp12.19, were identified in this bin. The newly developed translocation lines and the molecular markers and FISH probe will facilitate the application of the Th. ponticum-origin blue-grained characteristic in wheat breeding.

Nanoscale Fluorescent Metal-Organic Framework@Microporous Organic Polymer Composites for Enhanced Intracellular Uptake and Bioimaging.

Polymer-modified metal-organic frameworks combine the advantages of both soft polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge to develop simple methods for surface modification of MOFs. In this work, MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)-imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity, smaller size distribution, well-retained pore integrity, and available functional sites. After folic acid grafting, the enhanced intracellular uptake and bioimaging was validated.