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Brown stripe is a major fungal disease damaging the leaves of sugarcane. Breeding and cultivating resistant varieties is the most economical and effective method of controlling the disease. The paper reports on the evaluation of sugarcane brown stripe resistance in novel varieties bred by the China Sugarcane System and major varieties under cultivation in the sugarcane cultivating region. Field resistance against brown stripe was identified in 60 novel varieties and in 31 major varieties under cultivation in Lincang, Puer, and Yuxi, in Yunnan Province, and in Yizhou, Guangxi Province, where the incidence and severity of brown stripe is particularly high. Field surveys showed that 32 (53.3%) of the 60 novel varieties were highly resistant to moderately resistant, and 28 (46.7%) were susceptible to highly susceptible. In addition 21 (67.7%) out of the 31 major cultivated varieties were highly resistant to moderately resistant, and 10 (32.3%) were susceptible to highly susceptible. We recommend the intensifying of efforts to eliminate the major varieties that are susceptible, and promotion of the adoption of elite resistant varieties in wet and rainy sugarcane cultivating regions with high incidence and severity of sugarcane brown stripe disease, to effectively manage the brown stripe epidemic.

Background In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown. Methods Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR‐mutant non‐small cell lung cancer (NSCLC) patients treated with first‐ and second‐generation EGFR‐TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty‐eight patients were treated with third‐generation EGFR‐TKIs in the GLCI cohort. The BIM gene status was examined by next‐generation sequencing. Results The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first‐ and second‐generation EGFR‐TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild‐type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression‐free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third‐generation EGFR‐TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR‐TKIs, but not BIM deletion. Conclusions The presence of BIM deletion showed no relation to an impaired response to first‐, second‐, and third‐generation EGFR‐TKIs in NSCLC patients. The factors influencing the response of EGFR‐TKIs were concomitant genetic alterations, but not BIM deletion.

Leptomeningeal metastases (LM) had increased in advanced non-small-cell lung cancer (NSCLC) over the last 10 years. The survival outcome remained overall poor, heterogeneous and was reported in association with genotypes in lung cancer patients with LM. Graded prognostic assessment model integrated with molecular alterations (molGPA) might be accurate for outcome prediction of LM patients, but needs to be established.We retrospectively screened 8921 consecutive lung cancer patients from January 2011 to March 2018. A total of 301 patients diagnosed as LM were enrolled, and randomly divided into training and validation sets after stratified by gender and age. A molGPA score for each patient was calculated based on the weighted significant parameters including gene mutations.The median OS for the 301 patients was 9.2 months (95%CI: 7.9-10.5). In the training set, EGFR/ALK positivity, Karnofsky performance score (KPS) score≥60 and absence of extracranial metastasis (ECM) independently predicted better OS. We developed a molGPA model based on above significant prognostic factors. This molGPA model classified LM patients into three prognosis groups of high, intermediate and low risk (molGPA score of 0, 0.5-1.0 and 1.5-2.0, respectively. The median OS of high, intermediate and low risk LM patients in the training set was 0.3, 3.5 and 15.9 months, respectively (p 0.001). In the validation set, the median OS was 0.9, 5.8 and 17.7 months in the three molGPA subgroups, accordingly (p 0.001). The C-index of this model in training and validation sets was 0.70 (95%CI: 0.66-0.73) and 0.64 (95%CI: 0.58-0.70) respectively.The LM molGPA model with integration of gene status, KPS and ECM can accurately classify lung cancer patients with LM into diverse prognosis.

Background The lung is one of the most common target organs for malignant tumor metastasis. The existence of lung metastasis may have a decisive effect on the choice of treatment regimen. Minute pulmonary meningothelial-like nodules (MPMNs) usually present as ground-glass opacity or solid nodules, mimicking the imaging findings of malignant pulmonary nodules. This study summarizes the clinical, radiological, and pathological features of MPMNs to distinguish them from malignant pulmonary nodules. Methods The Guangdong Lung Cancer Institute Pathology Information System was searched using the key words "minute meningothelioid nodules" and "lung." Patients who underwent pulmonary resection from 23 February 2009 to 31 May 2017 were included in the study. The 11th edition of Rosai and Ackerman's Surgical Pathology was used to confirm the diagnosis. The clinical, imaging, and pathological characteristics of MPMNs were recorded. Results Twelve patients had MPMNs. MPMNs were associated with cancerous or precancerous lesions (10/12), female gender (11/12), and non-smokers (11/12). Four patients were misdiagnosed with malignant pulmonary nodules before surgery. Positron emission tomography-computed tomography revealed an increased maximum standardized uptake value in one patient. Immunohistochemistry identified eight specimens positive for vimentin, EMA, and PR and negative for TTF-1 and CK. Conclusions MPMNs tend to coexist with malignant tumors, mimicking the imaging findings of malignant pulmonary nodules, thus resulting in misdiagnosis. Dynamic monitoring or an invasive examination may help to distinguish MPMNs from malignant lesions.

In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 278 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, P = .380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223 ).

Sugarcane white leaf (SCWL) is a devastating sugarcane (Saccharum officinarum) disease caused by a 16SrXI group phytoplasma, which is extremely harmful to sugarcane production. To determine the occurrence of SCWL in different varieties in 2018, we conducted a field survey and performed nested PCR detection of SCWL phytoplasma in cane-planting areas of Mangweng and Hepai in Gengma, Yunnan province, which are the areas most severely affected by SCWL in China. The results of the field survey showed that the symptomatic incidence of SCWL differed among varieties. The mean symptomatic incidence of SCWL on variety Yuetang60 was the highest (73.50%), and it was the lowest on Liucheng05-136 (13.67%). Using nested PCR, the SCWL phytoplasma was detected in symptomatic plants of all varieties more than 90% of the time; the SCWL phytoplasma was detected in 91 and 97% of symptomatic plants of Yingyu91-59 and Liucheng05-136 varieties, respectively. The SCWL phytoplasma was detected by PCR in 82% of the asymptomatic plant samples. The results of this study showed that field survey based on white leaf symptoms did not accurately reflect the actual occurrence of the SCWL phytoplasma.

Sugarcane streak mosaic virus (SCSMV) is one of the most important pathogens associated with sugarcane mosaic disease. In recent years, the rapid spread of SCSMV in Yunnan province, China, has raised concerns. In this study, we analyzed 110 sugarcane samples with mosaic symptoms taken from main growing areas in Yunnan province. RT-PCR detection results showed that 94% samples were positive for SCSMV. We subsequently analyzed the genetic diversity and population structure of SCSMV based on the coat protein (CP) sequences of 48 isolates. The overall mean value of nucleotide diversity for all isolates was 0.01127 ± 0.00082. Phylogenetic analysis based on CP gene sequences showed that all the Chinese isolates were clustered into one group, showing a distinct geographic feature. Analysis of population structure showed that the population from this study is not genetically different from that in China, but is genetically different from populations from other countries. Our results suggest that SCSMV has become the main pathogen of sugarcane mosaic disease in Yunnan province, China and that the recent rapid spread of SCSMV in Yunnan is not due to the invasion of new SCSMV populations.

Sugarcane mosaic disease is one of the most serious and prevalent viral diseases of sugarcane in China. The use of resistant varieties is the most economical and effective measures for controlling this disease. Sugarcane streak mosaic virus (SCSMV) and Sorghum mosaic virus (SrMV) are the two predominant pathogens of mosaic disease in the cane-growing regions of China. In 2015, 2016, double resistance to SCSMV and SrMV was identified once a year using a combination of artificial stalk-cutting inoculation and RT-PCR detection in 71 new elite sugarcane varieties/clones. Of the 71 new elite sugarcane varieties/clones, 24 were highly (Grade 1) to moderately resistant (Grade 3), and 47 were susceptible (Grade 4) to highly susceptible (Grade 5) to SCSMV. Furthermore, 27 were highly (Grade 1) to moderately resistant (Grade 3), and 44 were susceptible (Grade 4) to highly susceptible (Grade 5) to SrMV. Fifteen new elite sugarcane varieties/clones were highly resistant (Grade 1) to resistant (Grade 2) to SCSMV and SrMV. While, five new elite sugarcane varieties/clones (Yuegan 34, Yuetang 55, Yunzhe 03–258, Yunzhe 05–51, Yunzhe 06–80) were highly resistant (Grade 1) to SCSMV and SrMV. We defined the resistance of 71 new elite sugarcane varieties/clones to the two main pathogens of mosaic disease and identified 15 resistant to both SCSMV and SrMV. These results provide an elite resistance resource for effective prevention and control of mosaic disease and may serve as a reference for commercial varieties.

Purpose: Chemoresistance in triple-negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacologic NOS inhibition on TNBC.Experimental Design: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS inhibitor (L-NMMA) for 24, 48, and 72 hours. Apoptosis was assessed by flow cytometry using Annexin-V and propidium iodide. Western blot was used to assess ER stress and apoptosis, and rtPCR was used to evaluate s-XBP1. TNBC patient-derived xenografts (PDX) were treated either with vehicle, docetaxel, or combination therapy (NOS inhibition + docetaxel). Mouse weight and tumor volumes were recorded twice weekly. Docetaxel concentration was determined using mass spectrometry. To quantify proliferation and apoptosis, PDX tumor samples were stained using Ki67 and TUNEL assay.Results: In vitro, L-NMMA ameliorated the iNOS upregulation associated with docetaxel. Apoptosis increased when TNBC cells were treated with combination therapy. In TNBC PDXs, combination therapy significantly reduced tumor volume growth and increased survival proportions. In the BCM-5998 PDX model, intratumoral docetaxel concentration was higher in mice receiving combination therapy. Coupling docetaxel with NOS inhibition increased EnR-stress response via coactivation of ATF4 and CHOP, which triggered the pASK1/JNK proapoptotic pathway, promoting cleavage of caspases 3 and 9.Conclusions: iNOS is a critical target for docetaxel resistance in TNBC. Pharmacologic inhibition of NOS enhanced chemotherapy response in TNBC PDX models. Combination therapy may improve prognosis and prevent relapse in TNBC patients who have failed conventional chemotherapy. Clin Cancer Res; 24(5); 1152–62. ©2018 AACR.

Brown rust, caused by Puccinia melanocephala has become a serious problem for sugarcane production in China. Therefore, 50 new elite varieties bred by the Chinese Sugarcane System were screened for brown rust resistance and the presence of a major resistance gene, Bru 1. Identification of field resistance and molecular detection of the brown rust resistance gene Bru 1 in the 50 new elite varieties and 2 main cultivated varieties were carried out in 2014 and 2015 at regional experimental stations of the China Sugarcane System in Dehong and Baoshan, Yunnan Province, where the incidence of brown rust is particularly high. Resistance evaluations based on ratings of symptom severity resulting from field infection showed that 32 (64%) of the 50 new elite varieties were highly resistant (n = 13, 26%), resistant (n = 16, 32%) and moderately resistant (n = 3, 6%). Molecular detection identified Bru 1 in 27 (54%) of these resistant varieties suggesting that brown rust resistance in these new elite varieties is primarily controlled by Bru 1. The absence of Bru 1 in the remaining five resistant suggested the presence of additional brown rust resistance genes. Two main cultivated varieties were highly resistant and Bru 1 - positive varieties. Different series differed in the frequencies of resistant and Bru 1 - positive varieties. Yunzhe series varieties had the highest frequency of resistant varieties (87.5%) and the highest frequency of Bru 1-positive varieties (81.3%); In contrast, the Yuetang series varieties had the lowest frequency of resistant varieties (40%) and the lowest frequency of Bru 1-positive varieties (30%). In this study, we defined the field resistance of 50 new elite varieties to brown rust, and determined the distribution of brown rust resistant gene Bru 1 in different series varieties. These results will provide new options for commercial production with effective resistance to brown rust. Moreover, these new elite resistant varieties can be used for subsequent breeding and selection to produce agronomically superior varieties with effective brown rust resistance.

DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regulates NHEJ and chemosensitivity in colon cancer cells. Using our recently developed NHEJ assay, we found that DSB introduction by I-SceI cleavage leads to Dicer upregulation. Dicer knockdown increased SIRT7 binding and decreased the level of H3K18Ac (acetylated lysine 18 of histone H3) at DSB sites, thereby repressing the recruitment of NHEJ factors to DSB sites and inhibiting NHEJ. Dicer overexpression reduced SIRT7 binding and increased the level of H3K18Ac at DSB sites, promoting the recruitment of NHEJ factors to DSBs and moderately enhancing NHEJ. Dicer knockdown and overexpression increased and decreased, respectively, the chemosensitivity of colon cancer cells. Dicer protein expression in colon cancer tissues of patients was directly correlated with chemoresistance. Our findings revealed a function of Dicer in NHEJ-mediated DSB repair and the association of Dicer expression with chemoresistance in colon cancer patients.

Brown rust caused by Puccinia melanocephala H. Sydow & P. Sydo is an important sugarcane disease that severely threatens sugarcane production in China. Breeding and planting resistant cultivars is the most cost-effective and efficient strategy for the control the disease. In addition, exploration, research, and utilization of resistant genes are the basis for resistance breeding. In the present study, four sugarcane varieties without the Bru1 gene and highly resistant to brown rust were used as male parents, and four varieties highly susceptible to brown rust were used as the female parents to configure hybrids. Six F1 hybrid populations were subjected to authenticity determination using SSR markers, brown rust resistance phenotype identification using artificial inoculation, and molecular detection of Bru1 gene. The results showed that the genetic segregation ratios in F1 hybrid populations of Yuetang 03-393 (HS) × ROC24 (HR) and Liucheng 03-1137 (HS) × Dezhe 93-88 (HR) were 3R:1S and 1R:3S, respectively, and Bru1 gene was not detected in their F1 hybrids. The results indicated that two dominant novel genes controlled brown rust resistance in Yuetang 03-393 (HS) × ROC24 (HR) and two recessive novel genes controlled brown rust resistance in Liucheng 03-1137 (HS) × Dezhe 93-88 (HR). Two genetically segregating populations that could be used for the localization of novel brown rust resistance genes were developed in the present study, and could lay a suitable foundation and provide theoretical reference for the analysis of the genetic mechanism of brown rust resistance, genetic map construction, mapping of novel resistance genes and the development of closely associated molecular markers in the future.

Background Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non–small-cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901). Patients and Methods The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors. Results All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = .009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = .004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = .001) and overall survival (P = .004) in patients. Conclusion Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.

In 2015, symptoms of red stripe were first viewed on leaves of sugarcane plants growing in Yuanjiang, Yunnan Province. Symptomatic leaf samples were collected from infected plants and isolations were made on NA medium. Pure culture isolates from resulting single colony were identified based on cultural and morphological characteristics as Acidovorax avenae subsp. avenae. Morphological identification was confirmed by sequence analysis of 16S rDNA. Pathogenicity tests confirmed Yunnan isolates of Acidovorax avenae subsp. avenae as the causal agent of red stripe on sugarcane. This is the first report of this disease in Yuanjiang, Yunnan, China. Field surveys showed that the sugarcane cultivar ‘Yunzhe03-194’ was highly susceptible, and disease incidence varied from 8 to 80%. Nine other sugarcane cultivars were found to be symptomless in the field. Further research is required to confirm the resistance levels of the sugarcane varieties.

Seventy-seven mosaic leaf samples from new sugarcane varieties from national regional trials in Kaiyuan, Mile and Yuanjiang, Yunnan Province, China, were collected in 2015 and analyzed using reverse-transcription polymerase chain reaction (RT-PCR) to determine the pathogen causing mosaic symptoms in sugarcane. Three viruses, Sugarcane streak mosaic virus (SCSMV), Sorghum mosaic virus (SrMV) and Sugarcane mosaic virus (SCMV), were detected in 100, 27.3 and 1.3% of the samples respectively. Co-infection with SCSMV, SrMV and SCMV was also found for the first time in the new variety Qiantang 5. Nucleotide sequences of the coat protein (CP) gene of 48 SCSMV and 17 SrMV isolates were subsequently sequenced and analyzed with the CP gene sequences of SCSMV and SrMV reported in GenBank to perform phylogenetic analyses. Geographic differences were observed in the phylogenetic tree of SCSMV and all SCSMV isolates from China clustered into a single China group. Moreover, SCSMV isolates from different new varieties were distributed across all subgroups or clustered into an independent branch in the China group. SrMV isolates obtained in this study and those published in GenBank clustered into two groups and were distributed into different subgroups within these groups. Furthermore, the distribution of SrMV isolates from different new varieties overlapped in these different groups and subgroups, with no obvious geographic differences. These results provide a scientific basis for sugarcane mosaic or streak mosaic disease resistance breeding and effective control of this disease.

The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The effectiveness of the interference was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction, and the cell proliferation was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed by subcutaneously inoculating the constructed cells into BALB/c nude mice. The protein expression levels of CRMP-4 were markedly increased in colon tumor tissue of the human samples. The proliferation of SW480 cells and the tumor growth rate in nude mice of the si-CPMR-4 group were evidently depressed compared with the si-scramble group. Thus, the present results suggest that CRMP-4 may be involved in the pathogenesis of CRC.

There has been growing concern over declines in populations of honey bees and other pollinators which are a vital part to our food security. It is imperative to identify factors responsible for accelerated declines in bee populations and develop solutions for reversing bee losses. While exact causes of colony losses remain elusive, risk factors thought to play key roles are ectoparasitic mites Varroa destructor and neonicotinoid pesticides. The present study aims to investigate effects of a neonicotinoid pesticide Imidacloprid and Varroa mites individually on survivorship, growth, physiology, virus dynamics and immunity of honey bee workers. Our study provides clear evidence that the exposure to sublethal doses of Imidacloprid could exert a significantly negative effect on health and survival of honey bees. We observed a significant reduction in the titer of vitellogenin (Vg), an egg yolk precursor that regulates the honey bees development and behavior and often are linked to energy homeostasis, in bees exposed to Imidacloprid. This result indicates that sublethal exposure to neonicotinoid could lead to increased energy usage in honey bees as detoxification is a energy-consuming metabolic process and suggests that Vg could be a useful biomarker for measuring levels of energy stress and sublethal effects of pesticides on honey bees. Measurement of the quantitative effects of different levels of Varroa mite infestation on the replication dynamic of Deformed wing virus (DWV), an RNA virus associated with Varroa infestation, and expression level of immune genes yields unique insights into how honey bees respond to stressors under laboratory conditions.

Sugarcane brown rust induced by Puccinia melanocephala is an important global disease. Bru1 is a major brown rust resistance gene and has been shown to provide broad-spectrum resistance against various brown rust pathogen strains originating from different countries. Thus, brown rust resistance genes have important implications for sugarcane brown rust resistance breeding programs. The objectives of this study were to (1) assess the level of resistance of common sugarcane crossbreeding parents to P. melanocephala, (2) determine the distribution of the Bru1 gene in common sugarcane crossbreeding parents in China, (3) screen, evaluate, and select rust-resistant parental lines to improve the efficiency of breeding for brown rust resistance. Brown rust resistance in 101 common sugarcane breeding parents was collected from the Chinese National Nursery of Sugarcane Germplasm Resources and was scored and identified at the seedling stage and was assayed for the presence of the brown rust resistance gene Bru1. The results showed that Bru1 was detected in 48 (47.5 %) resistant clones out of the 101 tested parental lines, indicating that brown rust resistance in common sugarcane breeding parents in China is primarily controlled by Bru1. The apparent absence of Bru1 from the other 29 resistant and 24 susceptible parental lines suggested that they may carry brown rust resistance-associated genes other than Bru1. These results may facilitate future efforts to breed varieties with improved resistance to brown rust and may provide additional resistant parental lines for selecting and planting elite-resistant varieties to effectively control brown rust disease in sugarcane.

Background: Resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) presents a major clinical challenge in advanced non-small cell lung cancer (NSCLC). Here, we report resistance mechanisms to abivertinib, a novel third-generation EGFR TKI, from a phase I dose-escalation/expansion study (NCT02330367). Methods: Patients with EGFR T790M-positive advanced NSCLC and progression on prior EGFR TKIs received abivertinib in dose escalation (50–350 mg twice daily [BID]) or expansion (300 mg BID) cohorts. Patients enrolled at Guangdong Lung Cancer Institute who underwent next-generation sequencing (NGS)-based genomic profiling upon abivertinib progression (prior to October 30, 2018) were enrolled in this exploratory analysis. Findings: Thirty of 73 patients enrolled were eligible for resistance analysis. Upon abivertinib progression, 27 patients provided plasma samples (six patients also provided paired samples from the progression sites) and three patients only provided tissue samples from the progression sites for NGS. A heterogeneous landscape of resistance to abivertinib was observed: 15% (4/27) experienced EGFR T790M loss and 13% (4/30) developing EGFR tertiary mutations including C797S. EGFR amplification was observed in 11 patients (37%), and considered a putative resistance mechanism in seven (23%) patients. Other EGFR-independent resistance mechanisms involved CDKN2A, MET, PIK3CA, HER2, TP53, Rb1 and small-cell lung cancer transformation. Interpretation: Our findings reveal a heterogenous pattern of resistance mechanisms to abivertinib which is distinct from that previously reported with osimertinib. EGFR amplification was the most common resistance mechanism in this cohort. Fund: The National Key R&D Program of China (Grant No. 2016YFC1303800), Key Lab System Project of Guangdong Science and Technology Department – Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2012A061400006/2017B030314120). Keywords: Abivertinib, Resistance mechanisms, EGFR T790M mutation, NSCLC, EGFR amplification

Background To evaluate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) by using immunohistochemistry analysis in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving cisplatin, fluorouracil, and docetaxel followed by concurrent chemoradiotherapy. Methods As part of a previously reported trial, 108 patients were enrolled in this study. Results We observed that Epstein-Barr Virus (EBV) antibody levels were associated with PD-1 positive staining in NPC and PD-1 positive staining was identified as an independent prognostic factor for progression-free survival (hazard ratio 0.363, 95% confidence interval 0.134-0.987, P = .047). By contrast, the correlation between the PD-L1 level and hemoglobin, lactate dehydrogenase and high-sensitivity C-reactive protein was not identified. Moreover, high levels of PD-L1 staining were not significantly associated with clinical outcomes. Conclusion NPC patients with negative PD-1 staining had a significantly reduced survival outcome. Furthermore, patients with positive PD-1 staining had significantly higher EBV antibody levels.

The molecular mechanisms of cervical cancer have been minimally explored with multi-omics data. In the present study, mRNA expression profiles were analyzed and combined with predicted miRNA interactions to contribute to the characterization of the underlying regulatory mechanisms of cervical cancer. A total of 92 significantly differentially expressed genes (DEGs) were identified in 33 tumor samples by comparison with 29 normal samples. mRNA-miRNA interaction network analysis revealed that 16 out of the 92 DEGs, including checkpoint kinase 1 (CHEK1), SRY-box 17 (SOX17), centrosomal protein 55, cyclin dependent kinase inhibitor 2A (CDKN2A), and inhibitor of DNA binding 4, were the targets of 4 miRNAs which were previously reported to be involved in the regulation of cervical cancer. Tumor and normal samples could be distinctly classified into two groups based on the expression of the 16 DEGs. Furthermore, survival analysis using the SurvExpress database indicated that the 16 DEGs could individually significantly differentiate low- and high-risk cervical cancer groups. Overall, multiple biological processes are likely to participate in the progression of cervical cancer based on the pathway and function enrichment identified for the DEGs. The dysregulation of SOX17 is associated with the regulation of embryonic development, the determination of cell fate and likely promotes cancer cell transformation. The dysregulation of CHEK1 and CDKN2A further promote cancer cell proliferation by affecting the cell cycle checkpoint in response to DNA damage. The identification of critical genes and biological processes associated with cervical cancer may be beneficial for the exploration of the molecular mechanisms.

Sugar cane white leaf (SCWL) is a serious disease caused by phytoplasmas. In this study, we performed nested PCR with phytoplasma universal primer pairs (P1/P7 and R16F2n/R16R2) for the 16S rRNA gene to detect SCWL phytoplasmas in 31 SCWL samples collected from Baoshan and Lincang, Yunnan, China. We cloned and sequenced the nested PCR products, revealing that the 16S rRNA gene sequences from 31 SCWL samples were all 1247 bp in length and shared more than 99 % nucleotide sequence similarity with the 16S rRNA gene sequences of SCWL phytoplasmas from various countries. Based on the reported 16S rRNA gene sequence data from SCWL isolates of various countries, we conducted phylogenetic and virtual RFLP analysis. In the resulting phylogenetic tree, all SCWL isolates clustered into two branches, with the Lincang and Baoshan SCWL phytoplasma isolates belonging to different branches. The virtual RFLP patterns show that phytoplasmas of the Lincang branch belong to subgroup 16SrXI-B. However, the virtual RFLP patterns revealed by HaeIII digestion of phytoplasmas of the Baoshan branch differed from those of subgroup 16SrXI-B. According to the results of phylogenetic and virtual RFLP analysis, we propose that the phytoplasmas of the Baoshan branch represent a new subgroup, 16SrXI-D. These findings suggest that SCWL is caused by phytoplasmas from group 16SrXI, including subgroup 16SrXI-B and a new subgroup, 16SrXI-D.

Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.

There are more than 120 sugarcane diseases that have been found in the world presently (Chen 1982; Rott et al. 2000), and more than 60 have been reported in China (The important sugarcane diseases research cooperation group 1991; Lu et al. 1997; Huang and Li 2014, 2016). Mastering the disease types, damage, and distribution in the sugarcane area can provide scientific basis for the sugarcane disease-resistance breeding, quarantine of introduced varieties, and disease management and research. Sugarcane production areas in China have drought in winter and spring and hot climate and good rainfall in summer and autumn. With the rise of temperature in spring, in case of cold current as well as the rainfall and temperature decline and the poor management, planted sugarcane in winter and this season are easily infected by pineapple disease and the ratoon crops are easily damaged by red rot disease. Because the whole seedling stage is in the dry season, smut becomes substantial causing sparse breakup. After June, with the high temperature and humidity, eyespot, brown stripe, yellow spot, pokkah boeng, rust, ring spot, and leaf scorch diseases are easily occurring and epidemic. Especially in recent years, introducing seedcanes frequently and transposing seedcanes in sugarcane planting area make some dangerous seedcane-transmitted diseases (ratoon stunting disease, mosaic, smut, yellow leaf syndrome, etc.) which are spread by seedcane between sugarcane areas. Then, caused sugarcane diseases occur commonly and damage more severely; have a serious impact on sugarcane yield, quality, and ratooning capacity; and bring serious hidden trouble to the safe production of sugarcane. In order to scientifically control the spread and damage of sugarcane disease, enhancing the capabilities of disaster prevention and reduction and ensuring the quality of sugarcane variety and safety of sugarcane production in 20 diseases that commonly occur in sugarcane production are systematically described in this chapter with clear-colored photos and scientific, accurate words. The content includes the occurrence and damage, identification of symptoms, characteristics of epidemic infection, and control measures.

Background This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients and methods Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1–3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. Results A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Conclusion Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

Studies have shown that pig manure is a reservoir of antibiotic resistance genes (ARGs). However, little is known about the characteristics of ARGs in the manure of piglets and adult pigs fed on different diets. In the present study, the ARG characteristics of the manure of piglets and adult pigs fed on different diets (feed, grain) were analyzed using high-throughput fluorescence quantitative PCR. Correlations between heavy metals, antibiotics, and ARGs in pig manure were analyzed. The results showed that the heavy metal and antibiotic contents in the manure of pigs receiving feed significantly exceeded those in the manure of pigs receiving grain. The heavy metal and antibiotic contents were higher in manure of piglets than in that of adult pigs. Feed significantly increased the ARG diversity in the pig manure. The ARG diversity was higher in manure of piglets than in that of adult pigs. In the manure of pigs receiving feed, 25 (from piglets), 12 (from adult pigs) ARGs were enriched significantly compared with pig fed with grain. In particular, sat4 (in piglets) and vatE-01 (in adult pigs) showed the highest enrichment, being increased by 59 and 19-fold, respectively. The ARG diversity correlated positively with the concentrations of antibiotics and heavy metals in the manure.

It has become increasingly clear that gut bacteria play vital roles in the development, nutrition, immunity, and overall fitness of their eukaryotic hosts. We conducted the present study to investigate the effects of gut microbiota disruption on the honey bee's immune responses to infection by the microsporidian parasite Nosema ceranae. Newly emerged adult workers were collected and divided into four groups: Group I-no treatment; Group II-inoculated with N. ceranae, Group III-antibiotic treatment, and Group IV-antibiotic treatment after inoculation with N. ceranae. Our study showed that Nosema infection did not cause obvious disruption of the gut bacterial community as there was no significant difference in the density and composition of gut bacteria between Group I and Group II. However, the elimination of gut bacteria by antibiotic (Groups III and IV) negatively impacted the functioning of the honey bees' immune system as evidenced by the expression of genes encoding antimicrobial peptides abaecin, defensin1, and hymenoptaecin that showed the following ranking: Group I > Group II > Group III > Group IV. In addition, significantly higher Nosema levels were observed in Group IV than in Group II, suggesting that eliminating gut bacteria weakened immune function and made honey bees more susceptible to Nosema infection. Based on Group IV having displayed the highest mortality rate among the four experimental groups indicates that antibiotic treatment in combination with stress, associated with Nosema infection, significantly and negatively impacts honey bee survival. The present study adds new evidence that antibiotic treatment not only leads to the complex problem of antibiotic resistance but can impact honey bee disease resistance. Further studies aimed at specific components of the gut bacterial community will provide new insights into the roles of specific bacteria and possibly new approaches to improving bee health.

Sugarcane streak mosaic virus (SCSMV) causes mosaic and streak symptoms on sugarcane and sorghum crops, and has a broad host range. SCSMV is a member of the genus Poacevirus in the family Potyviridae. Ten SCSMV isolates were collected from sugarcane plants showing mosaic and streaking in Southern China from 2009–2011. Sequence-based phylogenetic and population genetic analyses were conducted using four partial genomic sequences covering the full genomes. These analyses were used to estimate the subpopulation differentiation and divergence within the Chinese virus population, and were compared with isolates from India. SCSMV-infected sugarcane plants in the field commonly harbor virus quasispecies (mutant cloud), and often have mixed infections with the same virus isolates. Inter- and intra-lineage recombination sites were identified in the protein 1, helper-component proteinase, coat protein and 3′ non-coding regions of the Chinese isolates. All the Chinese non-recombinant isolates fell into at least nine lineages, and many clustered with Indian isolates. However, estimates of genetic differentiation and gene flow indicated that the SCSMV populations in China and India are genetically independent. Our genetic study of a poacevirus population in South Asia regions indicates the importance of the evolutionary-based design to control viruses.

Retraction The authors have retracted this article [1] because of significant overlap of text and some images with a previously published article by Xu et al. [2]. A formal investigation by the 1st Affiliated Hospital of Wenzhou Medical University has found that some panels in Fig. 6b [1] are identical with panels in Fig. 5a [2] and some images of mice lungs in Fig. 6c [1] are identical with images in Fig. 3g [2]. The data reported in this article are therefore unreliable. All authors agree to this retraction.

Leaf scald caused by Xanthomonas albilineans (Ashby) Dowson is a destructive disease of sugarcane, as it causes severe economic losses (Rott et al. 1995). X. albilineans has been reported in over 60 countries in Africa, Asia, and North and South Americas (Rott et al. 2000), but has so far not been reported in mainland China. X. albilineans is a quarantine pathogen for sugarcane germplasm imported into China. In June 2016, symptoms of leaf scald were observed on the newly-bred sugarcane cultivars ‘Guitang46’ and ‘Guitang06-2081’ in Beihai, Laibin and Baise, Guangxi province, China. The average disease incidence of cultivars ‘Guitang46’ and ‘Guitang06-2081’ was 44.6% and 50.1%, respectively. Typical symptoms of the disease were white stripes along veins. Severely infected plants also exhibited shorter stalk internodes, smaller leaves, and abnormal development of side shoots along the stalk. Leaves of side shoots had similar white stripes as those observed at the top of the stalk. A sudden wilting of all lea...

Background Recent evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of cellular processes and are found to be dysregulated in a variety of cancers. LINC00261 is an lncRNA that is aberrantly expressed in gastric cancer (GC). The clinical role of LINC00261 in GC and molecular mechanisms remains to be found. Methods Real-time polymerase chain reaction (PCR) was used to examine LINC00261 expression in GC cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Gain and loss of function approaches were used to investigate the biological role of LINC00261 in GC cells. The effects of LINC00261 on cell viability were evaluated by MTT and colony formation assays. Wound healing assay, cell migration and invasion assays, and nude mice were used to examine the effects of LINC00261 on tumor cell metastasis in vitro and in vivo. Protein levels of LINC00261 targets were determined by western blot and immunohistochemistry. Results LINC00261 was downregulated in GC cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low LINC00261 expression was correlated with deeper tumor invasion (P