Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD‐1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II‐IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab‐paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1‐3) of each 21‐day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2‐year progression‐free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%‐48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%‐70.4%) and treatment‐related adverse events (TRAEs) of low severity (grade 1‐2, 75.0%; grade 3, 10.7%; grade 4‐5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2‐year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long‐term survival analyses.

BackgroundSugarcane (Saccharum officinarum L.) is an important sugar crop which belongs to the grass family and can be used for fuel ethanol production. The growing demands for sugar and biofuel is asking for breeding a sugarcane variety that can shed their leaves during the maturity time due to the increasing cost on sugarcane harvest.ResultsTo determine leaf abscission related genes in sugarcane, we generated 524,328,950 paired reads with RNA-Seq and profiled the transcriptome of new born leaves of leaf abscission sugarcane varieties (Q1 and T) and leaf packaging sugarcane varieties (Q2 and B). Initially, 275,018 transcripts were assembled with N50 of 1,177 bp. Next, the transcriptome was annotated by mapping them to NR, UniProtKB/Swiss-Prot, Gene Ontology and KEGG pathway databases. Further, we used TransDecoder and Trinotate to obtain the likely proteins and annotate them in terms of known proteins, protein domains, signal peptides, transmembrane regions and rRNA transcripts. Different expression analysis showed 1,202 transcripts were up regulated in leaf abscission sugarcane varieties, relatively to the leaf packaging sugarcane varieties. Functional analysis told us 62, 38 and 10 upregulated transcripts were involved in plant-pathogen interaction, response to stress and abscisic acid associated pathways, respectively. The upregulation of transcripts encoding 4 disease resistance proteins (RPM1, RPP13, RGA2, and RGA4), 6 ABC transporter G family members and 16 transcription factors including WRK33 and heat stress transcription factors indicate they may be used as candidate genes for sugarcane breeding. The expression levels of transcripts were validated by qRT-PCR. In addition, we characterized 3,722 SNPs between leaf abscission and leaf packaging sugarcane plants.ConclusionOur results showed leaf abscission associated genes in sugarcane during the maturity period. The output of this study provides a valuable resource for future genetic and genomic studies in sugarcane.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2552-2) contains supplementary material, which is available to authorized users.

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BackgroundOsteosarcoma is the most common bone cancer, mainly occurring in children and adolescents, among which distant metastasis (DM) still leads to a poor prognosis. Although nomogram has recently been used in tumor areas, there are no studies focused on diagnostic and prognostic evaluation of DM in primary osteosarcoma patients.MethodsThe data of osteosarcoma patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in osteosarcoma patients, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors of osteosarcoma patients with DM. We then established two novel nomograms and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultA total of 1,657 patients with osteosarcoma were included, and 267 patients (16.11%) had DM at the time of diagnosis. The independent risk factors for DM in patients with osteosarcoma include age, grade, T stage, and N stage. The independent prognostic factors for osteosarcoma patients with DM are age, chemotherapy and surgery. The results of ROC curves, calibration, DCA, and Kaplan–Meier (K-M) survival curves in the training, validation, and expanded testing sets, confirmed that two nomograms can precisely predict occurrence and prognosis of DM in osteosarcoma patients.ConclusionTwo nomograms are expected to be effective tools for predicting the risk of DM for osteosarcoma patients and personalized prognosis prediction for patients with DM, which may benefit clinical decision-making.

BackgroundAlthough the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC.MethodsWe performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study.ResultsWe identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1.ConclusionsOur result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0925-7) contains supplementary material, which is available to authorized users.

Silicon (Si) plays an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticide use is a big challenge nowadays. The use of Si has been proven to be an environmentally sound way of enhancing crop productivity by facilitating plant growth and development through either a direct or indirect mechanism, especially in tropical and subtropical regions. In particular, it has been investigated for its role in water stress management. The aim of the current experiment was to examine the protective role of Si in the photosynthetic capacity of different leaf segments and the ultrastructure of sugarcane ( Saccharum officinarm ) plants under water stress. Sugarcane cv. GT 42 plants were supplied with 0, 100, 300, and 500 mg L –1 Si and exposed for 60 days under each stress condition such as 100–95, 55–50, and 35–30% of field capacity. For the photosynthetic responses, each leaf was observed and separated into three equal parts (base, middle, and tip). We used intact leaves and were able to assess leaf photosynthetic responses. Under moderate and severe stress conditions, applied Si increased the photosynthesis (base, ∼16–143%; middle, 20–66%; and tip leaf part, 41–71%), transpiration rate (base, 15–97%; middle, 26–68%; and tip leaf part, 6–61%), and stomatal conductance (base, 26–137%; middle, 12–70%; and tip leaf part, 7–75%) in sugarcane plants. Ultrastructural examination of sugarcane leaves using scanning electron microscopy showed the remarkable effects on stomata ultrastructure. Silicon increased plant growth development, photosynthetic efficiency, and biomass/yield, and promoted better adaptation of stomata to drought. This study suggests that the application of Si may be used to increase the stress tolerance of sugarcane plants.

Abscisic acid (ABA) can induce rapid stomatal closure in seed plants, but the action of this hormone on the stomata of fern and lycophyte species remains equivocal. Here, ABA-induced stomatal closure, signaling components, guard cell K+ and Ca2+ fluxes, vacuolar and actin cytoskeleton dynamics, and the permeability coefficient of guard cell protoplasts (Pf) were analyzed in species spanning the diversity of vascular land plants including 11 seed plants, 6 ferns and one lycophyte. We found that all 11 seed plants exhibited ABA-induced stomatal closure, but the fern and lycophyte species did not. ABA-induced hydrogen peroxide elevation was observed in all species, but the signaling pathway downstream of nitric oxide production, including ion channel activation, was only observed in seed plants. In the angiosperm faba bean (Vicia faba), ABA application caused large vacuolar compartments to disaggregate, actin filaments to disintegrate into short fragments and Pf to increase. None of these changes was observed in the guard cells of the fern Matteuccia struthiopteris and lycophyte Selaginella moellendorffii treated with ABA, but a hypertonic osmotic solution did induce stomatal closure in fern and the lycophyte. Our results suggest that there is a major difference in the regulation of stomata between the fern and lycophyte plants and the seed plants. Importantly, these findings have uncovered the physiological and biophysical mechanisms that may have been responsible for the evolution of a stomatal response to ABA in the earliest seed plants.

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