Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Keypoint-Aware Single-Stage 3D Object Detector for Autonomous Driving.

Current single-stage 3D object detectors often use predefined single points of feature maps to generate confidence scores. However, the point feature not only lacks the boundaries and inner features but also does not establish an explicit association between regression box and confidence scores. In this paper, we present a novel single-stage object detector called keypoint-aware single-stage 3D object detector (KASSD). First, we design a lightweight location attention module (LLM), including feature reuse strategy (FRS) and location attention module (LAM). The FRS can facilitate the flow of spatial information. By considering the location, the LAM adopts weighted feature fusion to obtain efficient multi-level feature representation. To alleviate the inconsistencies mentioned above, we introduce a keypoint-aware module (KAM). The KAM can model spatial relationships and learn rich semantic information by representing the predicted object as a set of keypoints. We conduct experiments on the KITTI dataset. The experimental results show that our method has a competitive performance with 79.74% AP on a moderate difficulty level while maintaining 21.8 FPS inference speed.

Correlation between antibiotic use in childhood and subsequent inflammatory bowel disease: a systematic review and meta-analysis.

Background: Antibiotic use leads to a cascade of inflammatory reaction in the gastrointestinal tract due to its association with a temporary disruption of human microbiome.Objectives: To explore the undetermined correlation between antibiotic use in childhood and subsequent inflammatory bowel disease (IBD).Methods: PUBMED, EMBASE and Cochrane Central Register of Controlled Trials were searched to identify related articles. We extracted and pooled the (adjusted) odds ratio (OR) and (adjusted) risk ratio (RR).Results: This systematic review and meta-analysis included 11 studies. The pooled OR of all 11 studies was 1.5 (95% confidence interval (CI): 1.22-1.85). The pooled ORs of the subsequent Crohn's disease and ulcerative colitis after antibiotic use in childhood were 1.59 (95% CI: 1.06-2.4) and 1.22 (95% CI: 0.82-1.8). The sensitivity analysis showed no change. The meta-regression showed there was not statistical significance for the publication year, research area and research methods. Egger's test showed publication bias in the IBD studies (p = .006 < .05) but no publication bias for the CD (p = .275>.05) and UC studies (p = .537>.05).Conclusions: There was a positive association between antibiotic use in childhood and the subsequently risk of Crohn's disease in non-European countries in the west during 2010-2013. Children in the United States taking antibiotics will have a higher risk of subsequently IBD than Europe, Asia and Australia. Registration number: CRD42019147648 (PROSPERO).

Effect of Broussonetia papyrifera L. silage on blood biochemical parameters, growth performance, meat amino acids and fatty acids compositions in beef cattle.

OBJECTIVE: The study was conducted to investigate the effects of Broussonetia papyrifera L.(B. papyrifera) silage on growth performance, serum biochemical parameters, meat quality, and meat amino acids and fatty acids compositions in beef cattle. METHODS: Sixty-four male Angus beef cattle were assigned to 4 groups with 4 pens in each group and 4 beef cattle in each pen, and fed with the total mixed ration supplemented with 0%, 5%, 10%, or 15% B. papyrifera silage for 100 days (control group, 5% group, 10% group and 15% group) separately. RESULTS: Beef cattle had significantly higher final body weight (BW) in 15% group, higher average daily gain (ADG) and dry matter intake (DMI) in 5% group, 10% group and 15% group, and higher feed conversion ratio (FCR) in 10% group and 15% group. Significantly higher blood superoxide dismutase (SOD) concentration was noted in 15% group, higher blood total antioxidant capacity (TAC) in 10% group and 15% group, lower 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 15% group. Meat had lower pH in 15% group, higher Commission International DeI'Eclairage (CIE) L* in 5% group, 10% group, and 15% group, and lower drip loss in 15% group. Greater concentration of meat polyunsaturated fatty acids (PUFA) was observed in 10% group and 15% group, and docosahexaenoic acid (DHA) in 15% group. CONCLUSION: Diet with 15% B. papyrifera silage could improve performance and increase final BW, ADG, DMI, and FCR, enhance the antioxidant functions by decreasing blood 8-OHdG and MDA and increasing blood SOD and TAC, improve the meat quality by lowing pH and drip loss and increasing CIE L*, increase the meat PUFA and DHA concentration. Polyphenols and flavonoids might be the main components responsible for the antioxidant activity and anti-biohydrogenation in the B. papyrifera silage. And B. papyrifera silage could be used as a new feedstuff in beef cattle nutrition.

Transcriptional analysis of host responses to Marek's disease virus infection in chicken thymus.

Marek's disease virus (MDV) is a cell-associated alpha-herpesvirus that causes T-cell lymphomas and nervous disorders in chickens. Different from other lymphoid organs, the thymus is the site of T-cell maturation and differentiation. However, the transcriptional response to MDV infection in the chicken thymus is still not known. In this study, we performed genome-wide expression analysis in thymus tissues of RB1B-infected chickens at different time points to investigate the molecular mechanisms of MDV pathogenesis. The number of differentially expressed genes with 2-fold or higher changes (>2) are as follows: 1,250 genes (7 dpi), 834 genes (14 dpi), 1,958 genes (21 dpi), and 2,306 genes (28 dpi). Gene ontology enrichment analysis revealed that the upregulated genes were involved in immune and inflammatory response at 7 dpi; angiogenesis, cytoskeleton organization, cell adhesion, and signal transduction showed different expressions at 21 and 28 dpi. The expression pattern of 18 randomly selected genes was confirmed by real-time RT-PCR. Several differently expressed host genes associated with tumor development are discussed. We identified the global host-gene expression pattern in the thymus of chickens that responded to MDV infection. The present data may provide groundwork for future investigation in the biology and pathogenesis of MDV.

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvß3 in melanoma cancer cells.

BACKGROUND: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvß3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells. RESULTS: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvß3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41). CONCLUSION: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

Catalytic activation of peracetic acid for pelargonic acid vanillylamide degradation by Co3O4 nanoparticles in-situ anchored carbon-coated MXene nanosheets: Performance and mechanism insight.

Pelargonic acid vanillylamide (PAVA), a capsaicin-type dacryagogue agent utilized for counter-terrorism and riot control, possesses a low stimulus threshold. This characteristic can lead to environmental contamination following its application and may easily result in secondary stimulation to personnel. Cobalt-doped Ti3C2-MXene nanosheets (Co3O4/Ti3C2@C) were synthesized for the purpose of activating peracetic acid (PAA) and degrading PAVA. A carbon layer was coated on the surface of Ti3C2-MXene nanosheets to address the challenge of poor oxygen resistance in MXenes, thus preventing a significant decline in surface reactivity. The BET surface area of Co3O4/Ti3C2@C was expanded to 149.6 m2/g, significantly exceeding that of Ti3C2 (13.0 m2/g) and Co3O4 (56.4 m2/g). With 0.5 mg/mL of Co3O4/Ti3C2@C and 0.35 mM of PAA, 100 mg/L of PAVA was completely degraded within 60 min. The augmented BET surface area and the presence of more active sites confer remarkable PAA activation and catalytic degradation properties toward PAVA. Parameters such as initial pH, PAVA concentration, catalyst dosage, and PAA concentration on PAVA degradation were systematically assessed. Furthermore, the reusability and stability of the nanocomposite were substantiated through recycling tests. Radical quenching experiments and electron paramagnetic resonance analysis demonstrated the acetylperoxy radical (CH3CO3) as the primary species responsible for PAVA degradation. This research serves as an illustration of the utilization of MXene and transition metal activated PAA in wastewater treatment.

Comparative transcriptome and methylome of polar bears, giant and red pandas reveal diet-driven adaptive evolution.

Epigenetic regulation plays an important role in the evolution of species adaptations, yet little information is available on the epigenetic mechanisms underlying the adaptive evolution of bamboo-eating in both giant pandas (Ailuropoda melanoleuca) and red pandas (Ailurus fulgens). To investigate the potential contribution of epigenetic to the adaptive evolution of bamboo-eating in giant and red pandas, we performed hepatic comparative transcriptome and methylome analyses between bamboo-eating pandas and carnivorous polar bears (Ursus maritimus). We found that genes involved in carbohydrate, lipid, amino acid, and protein metabolism showed significant differences in methylation and expression levels between the two panda species and polar bears. Clustering analysis of gene expression revealed that giant pandas did not form a sister group with the more closely related polar bears, suggesting that the expression pattern of genes in livers of giant pandas and red pandas have evolved convergently driven by their similar diets. Compared to polar bears, some key genes involved in carbohydrate metabolism and biological oxidation and cholesterol synthesis showed hypomethylation and higher expression in giant and red pandas, while genes involved in fat digestion and absorption, fatty acid metabolism, lysine degradation, resistance to lipid peroxidation and detoxification showed hypermethylation and low expression. Our study elucidates the special nutrient utilization mechanism of giant pandas and red pandas and provides some insights into the molecular mechanism of their adaptive evolution of bamboo feeding. This has important implications for the breeding and conservation of giant pandas and red pandas.

Multi-omics and Multi-VOIs to predict esophageal fistula in esophageal cancer patients treated with radiotherapy.

OBJECTIVE: This study aimed to develop a prediction model for esophageal fistula (EF) in esophageal cancer (EC) patients treated with intensity-modulated radiation therapy (IMRT), by integrating multi-omics features from multiple volumes of interest (VOIs). METHODS: We retrospectively analyzed pretreatment planning computed tomographic (CT) images, three-dimensional dose distributions, and clinical factors of 287 EC patients. Nine groups of features from different combination of omics [Radiomics (R), Dosiomics (D), and RD (the combination of R and D)], and VOIs [esophagus (ESO), gross tumor volume (GTV), and EG (the combination of ESO and GTV)] were extracted and separately selected by unsupervised (analysis of variance (ANOVA) and Pearson correlation test) and supervised (Student T test) approaches. The final model performance was evaluated using five metrics: average area under the receiver-operator-characteristics curve (AUC), accuracy, precision, recall, and F1 score. RESULTS: For multi-omics using RD features, the model performance in EG model shows: AUC, 0.817 ± 0.031; 95% CI 0.805, 0.825; p < 0.001, which is better than single VOI (ESO or GTV). CONCLUSION: Integrating multi-omics features from multi-VOIs enables better prediction of EF in EC patients treated with IMRT. The incorporation of dosiomics features can enhance the model performance of the prediction.

Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells.

BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. METHODS: The MCF-7 (EGFR +/-, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice. RESULTS: In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model. CONCLUSION: Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R.

Transcriptional profile of Marek's disease virus genes in chicken thymus during different phases of MDV infection.

In this study, 86 Marek's disease virus (MDV) transcripts were detected in chicken thymus infected with RB1B strain. Forty-seven of them, which were mainly involved in viral replication and immune escape, were detected at 7 days postinfection (dpi). Expression of most of the genes was increased at 21 and 28 dpi but reduced or shut down at 14 dpi. Unlike others tissues, we found that a latent infection was established at 14 dpi in infected thymus. Here, we show the kinetics of expression of MDV transcripts and their relative expression in infected thymus.

Retrospective cohort study on treatment modalities and survival time after oesophageal fistula in patients with oesophageal cancer in a regional cancer care centre in China.

BACKGROUND: Oesophageal fistula (perforation) is a devastating complication in patients with oesophageal cancer . The optimal treatment remains uncertain. OBJECTIVE: We sought to present real-world evidence on treatment modalities and survival postfistula in patients with oesophageal cancer. DESIGN, SETTINGS AND MAIN OUTCOMES: This was a retrospective cohort study of patients with oesophageal cancer with oesophageal fistulae diagnosed between June 2010 and June 2020 in a regional cancer care centre in Zhengzhou, China (n=352). The treatment options included surgical resection, oesophageal stent grafting, gastrostomy, nasogastric tube and conservative care. The primary outcome was survival time (months) postfistula. Inverse probability of treatment weighting (IPTW) life regression was used to estimate the differences in survival time accounting for potential confounders. RESULTS: The median survival time was 2.3 months (IQR: 0.7-6.0 months). Survival times were shorter in patients of male sex, T4 stage and oesophagotracheal versus oesophageal-mediastinal fistulae, and longer for any treatment option versus conservative care. The IPTW life regression analyses showed that in patients with oesophagotracheal fistulae, survival times were longer for stent grafting (+0.90 (95% CI 0.60 to 1.19) months) or gastrostomy (+0.81 (95% CI 0.47 to 1.13) months) versus nasogastric tube. In patients with oesophageal-mediastinal fistulae, survival times were shorter for stent grafting versus nasogastric tube (-0.36 (95% CI -0.63 to -0.09) months) and gastric tube (-0.29 (95% CI -0.50 to -0.08) months). Surgical resection was recorded in nine patients with oesophageal-mediastinal fistulae, and it was associated with the longest survival time in these patients. CONCLUSIONS: Stent grafting or gastrostomy may be preferable to nasogastric tube in survival prognosis for patients with oesophageal cancer with oesophagotracheal fistulae. In contrast, stent grafting may be not preferable to nasogastric tube or gastrostomy in survival prognosis for patients with oesophageal-mediastinal fistulae.

Development and Application of Potentially Universal Microsatellite Markers for Pheasant Species.

Pheasants are widely distributed in the southwest of China, but many of them are endangered due to habitat fragmentation and environmental changes. Genetic diversity is crucial for species to maintain their evolutionary potential, and thus it is important to develop universal genetic markers for facilitating the assessment of genetic diversity and planning effective conservation actions in these endangered species. In this study, 471 microsatellite loci which are common among eight pheasant species were screened based on genome data, and 119 loci were selected to develop microsatellite markers. After PCR amplifications and reaction condition optimizations, and validation of microsatellite loci in 14 species of 11 genera within Phasianidae. Finally, 49 potentially universal microsatellite markers in pheasant species were obtained. These microsatellite markers were successfully applied to assess the genetic diversity of 3 pheasant species. The Sichuan hill partridge (Arborophila rufipectus), blood pheasant (Ithaginis cruentus), buff-throated partridge (Tetraophasis szechenyii) and Sichuan hill partridge had a relatively low genetic diversity level. These 49 microsatellite loci are potentially universal microsatellite loci for pheasants and are of great significance to establish a shared platform in population genetics study of pheasants.

Analysis of protein expression profiles in the thymus of chickens infected with Marek's disease virus.

BACKGROUND: Marek's disease virus (MDV) is a highly cell-associated oncogenic α-herpesvirus that causes a disease characterised by T-cell lymphomas. The pathogenesis, or the nature of the interaction of the virus and the host, in the thymus are still unclear. RESULTS: In this study, we identified 119 differentially expressed proteins using two-dimensional electrophoresis and mass spectrometry from the thymuses of chickens infected with the RB1B strain of MDV. These differentially expressed proteins were found mainly at 21, 28 and 35 days post-infection. More than 20 of the differentially expressed proteins were directly associated with immunity, apoptosis, tumour development and viral infection and replication. Five of these proteins, ANXA1, MIF, NPM1, OP18 and VIM, were further confirmed using real-time PCR. The functional associations and roles in oncogenesis of these proteins are discussed. CONCLUSIONS: This work provides a proteomic profiling of host responses to MDV in the thymus of chickens and further characterises proteins related to the mechanisms of MDV oncogenesis and pathogenesis.

Anti-PD-L1 Antibody Enhances T Cell Immune Responses and Reduces Resistance of Breast Cancer Cells to Radiotherapy.

Immune escape is a frequent occurrence, which limits the duration of antitumor immune responses to radiotherapy. Here, we aimed to ascertain the roles and underlying mechanisms of programmed death ligand 1 (PD-L1) in tolerance of breast cancer (BC) to radiotherapy. We first quantified microRNA-21 (miR-21) and PD-L1 expression in BC tissues and cells, followed by identification of the interactions between miR-21, PD-L1, and programmed cell death protein 4 (PDCD4). miR-21 knock-in mice were used to construct tumor-bearing models, which were then treated with anti-PD-L1 antibody and irradiation, followed by measurement of tumor growth and tumor immune escape. Finally, we evaluated the synergistic effects of radiotherapy and anti-PD-L1 antibody in vivo. The results showed increased miR-21 expression in BC tissues and cells, which was positively correlated with PD-L1 expression. The treatment with radiotherapy or anti-PD-L1 antibody in the miR-21 knock-in mice diminished tumor weight and volume, along with decreased CD3+CD8+ positive cells, serum IL-2 and IFN-γ levels, and lower PD-L1 expression, but augmented apoptosis of T and BC cells. Moreover, miR-21 significantly augmented PD-L1 expression via PI3K/Akt pathway activation by targeting PDCD4 in BC cells. Thus, radiotherapy and anti-PD-L1 antibody synergistically accelerated the therapeutic effect against BC in mice, thereby implicating a close interplay between radiotherapy, T cells, and the miR-21/PDCD4/PI3K/Akt/PD-L1 axis.

Degradation of malathion in the solution of acetyl peroxyborate activated by carbonate: Products, kinetics and mechanism.

The degradation process of malathion in the acetyl peroxyborate (APB) solution of different APB/malathion molar ratio and in the carbonate-activated APB (APB/CO32-) solution of different pH was studied by 31P NMR technology. In the APB solution, all malathion could be degraded in 47.5 min when the molar ratio of APB/malathion was 60. CO32- could effectively activate APB to degrade all malathion in 10 min at pH of 10 when APB/malathion was 10, which was obviously higher than in APB solution. 1O2, •O2-, •OH and carbon-centered radicals (RC•) could be produced in the APB/CO32- solution, and the degradation of malathion was mainly affected by RC•. The degradation mechanism of malathion in the APB/CO32- solution was proposed based on the research results of malathion degradation process by 31P NMR and active species quenching test, which involves two steps: the first step is the oxidation of malathion to malaoxon by RC•, and the second step is the hydrolysis of malaoxon to dimethyl phosphate via hydroxyl anions nucleophilic addition.

Genome-Wide Identification of DNA Methylases and Demethylases in Kiwifruit (Actinidia chinensis).

DNA methylation plays an important role in a wide range of developmental and physiological processes in plants. It is primarily catalyzed and regulated by cytosine-5 DNA methyltransferases (C5-MTases) and a group of DNA glycosylases that act as demethylases. To date, no genome-scale analysis of the two kiwifruit (Actinidia chinensis) families has been undertaken. In our study, nine C5-MTases and seven DNA demethylase genes were identified in the kiwifruit genome. Through selective evolution analysis, we found that there were gene duplications in C5-MTases and demethylases, which may have arisen during three genome doubling events followed by selection during evolution of kiwifruit. Expression analysis of DNA methylases (C5-MTases) and demethylases identified changes in transcripts of DNA methylation and demethylation genes during both vegetative and reproductive development. Moreover, we found that some members of the two methylase/demethylase families may also be involved in fruit ripening and the regulation of softening. Our results help to better understand the complex roles of methylation/demethylation in plants and provide a foundation for analyzing the role of DNA methylation modification in kiwifruit growth, development and ripening.

Prognostic biological factors of radiation pneumonitis after stereotactic body radiation therapy combined with pulmonary perfusion imaging.

Radiation pneumonitis (RP) is one of the most common dose-limiting toxicity syndromes in patients with thoracic malignant tumors receiving radiotherapy. The present study aimed to identify biological factors for the prediction of RP. Pulmonary perfusion imaging is capable of reflecting the differential functional activity of various regions of the lung, and in the present study, radiotherapy plans that were established on the basis that pulmonary perfusion images have high biological conformality, which may identify regions vulnerable to RP to spare them from radiation. A total of 46 patients with non-small cell lung cancer (NSCLC), exhibiting high and low levels of apurinic/apyrimidinic endonuclease-1 (Ape-1), intercellular adhesion molecule (ICAM)-1 and interleukin (IL)-17A prior to treatment, with SBRT with respective cut-off values of 4.2, 3.0 and 5.1 µg/l were stratified into groups A and B. Patients received radiation doses within the margin of the planning target volume. Stereotactic body radiation therapy (SBRT) was used for the treatment of NSCLC and single-photon emission computed tomography pulmonary perfusion imaging was used to assess all patients for the presence of RP. Furthermore, the serum levels of Ape-1, ICAM-1 and IL-17A were examined by ELISA. Prior to SBRT, perfusion images indicated that no RP was present in any of the patients, and 23 patients had high levels of Ape-1, ICAM-1 and IL-17A. After SBRT, 22 out of 23 patients in group A (95.65%) presented with RP and 1 patient (4.35%) had no RP. In group B, 6 out of 23 patients (26.09%) had RP and 17 patients (73.91%) had no RP after SBRT. The difference between the two groups in the incidence of RP was significant (P=1.66×10-12 <0.05). In conclusion, high levels of Ape-1, ICAM-1 and IL-17A are associated with an increased risk of RP. A further analysis should be performed in the future to verify whether these factors have significant prognostic value.

A Chromosome-Scale Genome Assembly of Paper Mulberry (Broussonetia papyrifera) Provides New Insights into Its Forage and Papermaking Usage.

Paper mulberry (Broussonetia papyrifera) is a well-known woody tree historically used for Cai Lun papermaking, one of the four great inventions of ancient China. More recently, Paper mulberry has also been used as forage to address the shortage of feedstuff because of its digestible crude fiber and high protein contents. In this study, we obtained a chromosome-scale genome assembly for Paper mulberry using integrated approaches, including Illumina and PacBio sequencing platform as well as Hi-C, optical, and genetic maps. The assembled Paper mulberry genome consists of 386.83 Mb, which is close to the estimated size, and 99.25% (383.93 Mb) of the assembly was assigned to 13 pseudochromosomes. Comparative genomic analysis revealed the expansion and contraction in the flavonoid and lignin biosynthetic gene families, respectively, accounting for the enhanced flavonoid and decreased lignin biosynthesis in Paper mulberry. Moreover, the increased ratio of syringyl-lignin to guaiacyl-lignin in Paper mulberry underscores its suitability for use in medicine, forage, papermaking, and barkcloth making. We also identified the root-associated microbiota of Paper mulberry and found that Pseudomonas and Rhizobia were enriched in its roots and may provide the source of nitrogen for its stems and leaves via symbiotic nitrogen fixation. Collectively, these results suggest that Paper mulberry might have undergone adaptive evolution and recruited nitrogen-fixing microbes to promote growth by enhancing flavonoid production and altering lignin monomer composition. Our study provides significant insights into genetic basis of the usefulness of Paper mulberry in papermaking and barkcloth making, and as forage. These insights will facilitate further domestication and selection as well as industrial utilization of Paper mulberry worldwide.

[Correlations between Ape1/Ref-1, ICAM-1 and IL-17A Levels in Serum and Radiation Pneumonitis for Local Advanced Non-small Cell Lung Cancer Patients].

BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. METHODS: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. RESULTS: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. CONCLUSIONS: On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.