Systematic analysis of PANoptosis-related genes identifies XIAP as a functional oncogene in breast cancer.

BACKGROUND: Breast cancer (BC) is the most prevalent malignant disease affecting women globally. PANoptosis, a novel form of cell death combining features of pyroptosis, apoptosis, and necroptosis, has recently gained attention. However, its precise function in BC and the predictive values of PANoptosis-related genes remain unclear. METHODS: We used the expression data and clinical information of BC tissues or normal breast tissues from public databases, and then successfully developed and verified a BC PANoptosis-related risk model through a combination of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and Kaplan-Meier (KM) analysis. A nomogram was constructed to estimate survival probability, and its accuracy was assessed using calibration curves. RESULTS: Among 37 PANoptosis-related genes, we identified 4 differentially expressed genes related to overall survival (OS). Next, a risk model incorporating these four PANoptosis-related genes was established. Patients were stratified into low/high-risk groups based on the median risk score, with the low-risk group showing better prognoses and higher levels of immune infiltration. Utilizing the risk score and clinical features, we developed a nomogram to predict 1-, 3- and 5-year survival probability. X-linked inhibitor of apoptosis protein (XIAP) emerged as a potentially risky factor with the highest hazard ratio. In vitro experiments demonstrated that XIAP inhibition enhances the antitumor effect of doxorubicin through the PANoptosis pathway. CONCLUSION: PANoptosis holds an important role in BC prognosis and treatment.

Alteration of chromatin high-order conformation associated with oxaliplatin resistance acquisition in colorectal cancer cells.

Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high-order three-dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi-omics study by combining DLO Hi-C, ChIP-seq as well as RNA-seq technologies on the established oxaliplatin-resistant cell line HCT116-OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi-C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin-resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.

Multiomics strategies for decoding seed dormancy breakdown in Paris polyphylla.

BACKGROUND: The disruption of seed dormancy is a complicated process and is controlled by various factors. Among these factors, membrane lipids and plant hormones are two of the most important ones. Paris polyphylla is an important Chinese herbaceous species, and the dormancy trait of its seed limits the cultivation of this herb. RESULTS: In this study, we investigate the global metabolic and transcriptomic profiles of Paris polyphylla during seed dormancy breaking. Widely targeted metabolomics revealed that lysophospholipids (lysoPLs) increased during P. polyphylla seed dormancy breaking. The expression of phospholipase A2 (PLA2), genes correlated to the production of lysoPLs, up-regulated significantly during this process. Abscisic acid (ABA) decreased dramatically during seed dormancy breaking of P. polyphylla. Changes of different GAs varied during P. polyphylla seeds dormancy breaking, 13-OH GAs, such as GA53 were not detected, and GA3 decreased significantly, whereas 13-H GAs, such as GA15, GA24 and GA4 increased. The expression of CYP707As was not synchronous with the change of ABA content, and the expression of most UGTs, GA20ox and GA3ox up-regulated during seed dormancy breaking. CONCLUSIONS: These results suggest that PLA2 mediated production of lysoPLs may correlate to the seed dormancy breaking of P. polyphylla. The conversion of ABA to ABA-GE catalysed by UGTs may be the main cause of ABA degradation. Through inhibition the expression of genes related to the synthesis of 13-OH GAs and up-regulation genes related to the synthesis of 13-H GAs, P. polyphylla synthesized more bioactive 13-H GA (GA4) to break its seed dormancy.

Characterization of circSCL38A1 as a novel oncogene in bladder cancer via targeting ILF3/TGF-ß2 signaling axis.

The regulatory role of circRNAs in cancer metastasis has become a focused issue in recent years. To date, however, the discovery of novel functional circRNAs and their regulatory mechanisms via binding with RBPs in bladder cancer (BC) are still lacking. Here, we screened out circSLC38A1 based on our sequencing data and followed validation with clinical tissue samples and cell lines. Functional assays showed that circSLC38A1 promoted BC cell invasion in vitro and lung metastasis of mice in vivo. By conducting RNA pull-down, mass spectrum, and RIP assays, circSLC38A1 was found to interact with Interleukin enhancer-binding factor 3 (ILF3), and stabilize ILF3 protein via modulating the ubiquitination process. By integrating our CUT&Tag-seq and RNA-seq data, TGF-ß2 was identified as the functional target of the circSLC38A1-ILF3 complex. In addition, m6A methylation was enriched in circSLC38A1 and contributed to its upregulation. Clinically, circSLC38A1 was identified in serum exosomes of BC patients and could distinguish BC patients from healthy individuals with a diagnostic accuracy of 0.878. Thus, our study revealed an essential role and clinical significance of circSLC38A1 in BC via activating the transcription of TGF-ß2 in an ILF3-dependent manner, extending the understanding of the importance of circRNA-mediated transcriptional regulation in BC metastasis.

Characterisation of a novel transcript LNPPS acting as tumour suppressor in bladder cancer via PDCD5-mediated p53 degradation blockage.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a crucial role in tumour initiation and progression. However, little is known about their contributions to p53-related bladder cancer (BC) inhibition. METHODS: By using high-throughput sequencing, we screened the expression profiles of lncRNAs in BC and adjacent non-tumour tissues. The roles of a novel lncRNA, named LNPPS [a lncRNA for programmed cell death 5 (PDCD5) and p53 stability], were determined by gain- and loss-of-function assays. RNA pull-down followed by mass spectrometry analysis, RNA immunoprecipitation assays and other immunoprecipitation assays were performed to reveal the interactions among LNPPS, PDCD5 and p53, and the regulatory effect of LNPPS on the complex ubiquitination network comprising PDCD5, p53 and mouse double minute 2 homologue (MDM2). RESULTS: LNPPS was downregulated in BC and markedly inhibited the viability of BC cells by inducing PDCD5/p53-related apoptosis in vivo and in vitro. Mechanistically, LNPPS, serving as a scaffold, connected PDCD5 and p53 with nucleotides (nt) located at 121-251 nt and 251-306 nt of LNPPS, respectively. This process allowed LNPPS to protect PDCD5 from proteasomal degradation by blocking its K20 site ubiquitination. On the other hand, the increased interaction between PDCD5 and p53 displaced p53 from the MDM2-p53 ubiquitination complex, resulting in an increase in p53 expression and related apoptosis levels. Moreover, LNPPS could induce the accumulation of PDCD5 and p53 in the nucleus and exert a synergistic effect on the prevention of protein degradation. In addition, we confirmed that the downregulation of LNPPS in BC was mediated by the decreased N6-methyladenosine (m6 A) modification. CONCLUSION: Our findings highlight a novel cross-talk between LNPPS and the PDCD5/p53/MDM2 ubiquitination axis in BC development, indicating its potential as a therapeutic target for BC patients.

The anti-TMV potency of the tobacco-derived fungus Aspergillus versicolor and its active alkaloids, as anti-TMV activity inhibitors.

Nicotiana tabacum (tobacco) has attracted interest as one of the most economically important industrial crops widely cultivated in China, whose dried leaves are popularly consumed medicinally and recreationally by human societies. In this study, five undescribed alkaloids derivatives, isoaspergillines A-E, together with eight known alkaloids, notoamide D, (1R,4S)-4-benzyl-1-isopropyl-2,4-dihydro-1H-pyrazino-[2,1-b]quinazoline-3,6-dione, protuboxepin K, notoamide C, notoamide M, deoxybrevianamide E, cyclo (D-Pro-L-Trp), and versicolamide B, were obtained from the culture of the Nicotiana tabacum-derived fungus Aspergillus versicolor. Their structures were mainly elucidated through comprehensive analyses of spectroscopic data. Bioactivity evaluation of all isolated compounds revealed that isoaspergilline A and notoamide M exhibited anti-TMV activities with IC50 values of 20.0 and 22.8 µM, respectively. Molecular docking suggested that isoaspergilline A and notoamide M were well located into the active site of anti-TMV by interacting with SER138, SER143, and ASN73 residues. This study enlightens the therapeutic potential of the endophytic fungus A. versicolor and it is helpful to find undescribed anti-TMV activity inhibitors, as well as searching for new anti-TMV candidates from natural sources.

Isochromenes from the Nicotiana tabacum-derived endophytic fungus Aspergillus versicolor and their anti-tobacco mosaic virus activities.

Three new isochromenes, (5-methoxy-7-prenyl-1H-isochromen-3-yl)methanol (1), 3-(3-(hydroxymethyl)-5-methoxy-1H-isochromen-7-yl)propan-1-ol (2), and (5-methoxy-7-methyl-1H-isochromen-3-yl)methanol (3), along with three known analogues (4-6) were isolated from the fermentation products of a Nicotiana tabacum-derived endophytic fungus Aspergillus versicolor. Their structures were elucidated by spectroscopic methods, including extensive 1 D and 2 D NMR techniques. Compounds 1-3 and 6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 exhibited high anti-TMV activity with inhibition rate of 46.4%, and this rate is higher than that of positive control. Compounds 1, 3, and 6 also showed potential anti-TMV activity with inhibition rates of 28.6, 30.5, and 26.2%, respectively. The IC50 of compounds 1-3 and 6 were also tested, and showed IC50 values of 49.3, 22.4, 42.2, and 54.1 µM, respectively.

Perioperative Exhaled Nitric Oxide as an Indicator for Postoperative Pneumonia in Surgical Lung Cancer Patients: A Prospective Cohort Study Based on 183 Cases.

Introduction: This study is conducted to investigate the correlation between perioperative fractional exhaled nitric oxide and postoperative pneumonia (POP) and the feasibility of perioperative FeNO for predicting POP in surgical lung cancer patients. Methods: Patients who were diagnosed with non-small-cell lung cancer (NSCLC) were prospectively analyzed, and the relationship between perioperative FeNO and POP was evaluated based on patients' basic characteristics and clinical data in the hospital. Results: There were 218 patients enrolled in this study. Finally, 183 patients were involved in the study, with 19 of them in the POP group and 164 in the non-POP group. The POP group had significantly higher postoperative FeNO (median: 30.0 vs. 19.0 ppb, P < 0.001) as well as change in FeNO (median: 10.0 vs. 0.0 ppb, P < 0.001) before and after the surgery. For predicting POP based on the receiver operating characteristic (ROC) curve, a cutoff value of 25 ppb for postoperative FeNO (Youden's index: 0.515, sensitivity: 78.9%, and specificity: 72.6%) and 4 ppb for change in FeNO (Youden's index: 0.610, sensitivity: 84.2%, specificity: 76.8%) were selected. Furthermore, according to the bivariate regression analysis, FEV1/FVC (OR = 0.948, 95% CI: 0.899-0.999, P=0.048), POD1 FeNO (OR = 1.048, 95% CI: 1.019-1.077, P=0.001), and change in FeNO (OR = 1.087, 95% CI: 1.044-1.132, P < 0.001) were significantly associated with occurrence of POP. Conclusions: This prospective study revealed that a high postoperative FeNO (>25 ppb), as well as an increased change in FeNO (>4 ppb), may have the potential in detecting the occurrence of POP in surgical lung cancer patients.

Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulin-like growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-α (TNFα), and interleukins (IL) -1ß, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (-43.2%), IGF-I (-24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1ß and IL-10 were positively associated with THSD1+ EVs (P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress.

[Distribution Characteristics and Ecological and Health Risk Assessment of Phthalic Acid Esters in Surface Water of Qiandao Lake, China].

In order to reveal the pollution and risk level of phthalic acid esters (PAEs) in Qiandao Lake, six types of PAEs in 17 sampling points (in Qiandao Lake and its inflowing rivers) in dry and wet seasons were detected. The results showed that six types of PAEs were detected in both dry and wet seasons, with the concentrations of 0.98-5.33 µg·L-1 (average concentration 2.63 µg·L-1) in the dry season and 3.22-17.88 µg·L-1 (average concentration 7.99 µg·L-1) in the wet season. In terms of the detection rate and concentration of each monomer PAEs, DiBP, DBP, and DEHP were the main PAEs components in the water body. The measured value of DBP at 10 sampling points and its average mass concentration in the wet season were higher than the national standard (3 µg·L-1). Principal component analysis indicated that the main sources of PAEs were personal care products, plastics, and domestic waste. The pollution level of PAEs in Qiandao Lake was at a high level at home and abroad. The health risk assessment results in Qiandao Lake showed that the non-carcinogenic risk index of PAEs in the study area was less than 1, which would not produce non-carcinogenic risks to the human body. The carcinogenic risk index of children exceeded 10-6 at some points, indicating that it may pose carcinogenic risks to children, to which more attention should be paid.

Cyclopiazonic acid type indole alkaloids from Nicotiana tabacum-derived fungus Aspergillus versicolor and their anti-tobacco mosaic virus activities.

Indole alkaloids have attracted widespread attention of chemists and biologists. Therefore, the aim of this study is to screen more bioactivities indole alkaloids from the microorganisms. In this study, five undescribed CPA-type indole alkaloids, aspergillines F-J, and three known CPA-type indole alkaloids, aspergilline A, aspergilline C, and cyclopiamide E, were obtained from the Nicotiana tabacum-derived fungus Aspergillus versicolor. Notably, aspergillines F and G represent the first examples of indole alkaloids with a benzo[cd]indol-2(1H)-one skeleton, and aspergilline J is also the firstly obtained indole alkaloids bearing a N-1-(2-(1H-imidazole-5-yl)ethyl) moiety. Aspergillines F-J and cyclopiamide E were tested for their anti-TMV activities, and the results revealed that aspergillines G and J exhibited obvious anti-TMV activities with inhibition rates of 41.2 and 56.8% at the concentration of 20 µM, respectively. These rates are high than that of positive control (with inhibition rate of 32.5%). In addition, the molecular docking studies for the isolated CPA-type indole alkaloids may also reveal that the benzo[cd]indol-2(1H)-one substructure is the fundamental for anti-TMV activity and the oxygen-containing substituent groups at C-19 also increases the inhibitory activity. This study of structure-activity relationship is helpful to find new anti-TMV activity inhibitors.

PIWI-interacting RNAs are aberrantly expressed and may serve as novel biomarkers for diagnosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the main subtype of primary lung cancer and is a leading cause of cancer-related death worldwide. PIWI-interacting RNAs (piRNAs) are a type of small non-coding RNAs that may play crucial roles in cancer progression and serve as biomarkers for tumor detection. This study aimed to explore the expression profiles and diagnostic values of piRNAs in LUAD. METHODS: Small RNA sequencing was performed to investigate tissue piRNA profiles of LUAD. The expression of selected upregulated piRNAs were detected in tissues and serum exosome samples by quantitative real-time polymerase chain reaction (qRT-PCR). Serum exosomes were identified by transmission electron microscope, nanoparticle tracking analysis, and western blot analysis. Receiver operating characteristic (ROC) curve was adopted to quantify the diagnostic potentials of piRNAs in LUAD. Finally, a piRNA panel was developed by multivariate logistic regression model. RESULTS: We identified that 76 piRNAs were overexpressed and 9 piRNAs were underexpressed in LUAD tissues compared with adjacent non-tumor tissues. Among the top 10 overexpressed piRNAs, 4 piRNAs (piR-hsa-26925, piR-hsa-5444, piR-hsa-30636, and piR-hsa-8757) were verified by qRT-PCR to be significantly upregulated in LUAD tissues. Moreover, piR-hsa-26925 and piR-hsa-5444 had a significantly higher level in serum exosome samples of LUAD patients than those of healthy controls. We finally established a 2-piRNA panel composed of piR-hsa-26925 and piR-hsa-5444, which showed higher diagnostic performance for LUAD with an AUC of 0.833. CONCLUSIONS: Our finding revealed the abnormally expressed piRNAs in LUAD, and serum exosomal piR-hsa-26925 and piR-hsa-5444 could serve as potential biomarkers for LUAD diagnosis.

Long non-coding RNA ADAMTS9-AS1 suppresses colorectal cancer by inhibiting the Wnt/ß-catenin signalling pathway and is a potential diagnostic biomarker.

Long non-coding RNAs (lncRNAs) have come out as critical molecular regulators of human tumorigenesis. In this study, we sought to identify and functionally characterize lncRNAs as potential mediators of colorectal cancer progression. We screened and identified a novel lncRNA, ADAMTS9-AS1, which was significantly decreased in colorectal cancer tissues and was correlated with clinical outcome of patients according to The Cancer Genome Atlas (TCGA) database. In addition, ADAMTS9-AS1 regulated cell proliferation and migration both in vitro and in vivo. Bioinformatics analysis revealed that overexpression of lncRNA-ADAMTS9-AS1 preferentially affected genes that were linked to proliferation and migration. Mechanistically, we found that ADAMTS9-AS1 obviously suppressed ß-catenin, suggesting that Wnt signalling pathway participates in ADAMTS9-AS1-mediated gene transcriptional regulation in the suppression of colorectal tumorigenesis. Finally, we found that exosomal ADAMTS9-AS1 could serve as a diagnostic biomarker for colorectal cancer with AUC = 0.835 and 95% confidence interval = 0.777-0.911. Our data demonstrated that ADAMTS9-AS1 might play important roles in colorectal cancer by suppressing oncogenesis. Targeting ADAMTS9-AS1 may have potential clinical applications in colorectal cancer prognosis and treatment as an ideal therapeutic target. Finally, exosomal lncRNA-ADAMTS9-AS1 is a promising, novel diagnostic biomarker for colorectal cancer.

Using machine learning to predict ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) is one of the most common types of cancer in women. Accurately prediction of benign ovarian tumors (BOT) and OC has important practical value. METHODS: Our dataset consists of 349 Chinese patients with 49 variables including demographics, blood routine test, general chemistry, and tumor markers. Machine learning Minimum Redundancy - Maximum Relevance (MRMR) feature selection method was applied on the 235 patients' data (89 BOT and 146 OC) to select the most relevant features, with which a simple decision tree model was constructed. The model was tested on the rest of 114 patients (89 BOT and 25 OC). The results were compared with the predictions produced by using the risk of ovarian malignancy algorithm (ROMA) and logistic regression model. RESULTS: Eight notable features were selected by MRMR, among which two were identified as the top features by the decision tree model: human epididymis protein 4 (HE4) and carcinoembryonic antigen (CEA). Particularly, CEA is a valuable marker for OC prediction in patients with low HE4. The model also yields better prediction result than ROMA. CONCLUSION: Machine learning approaches were able to accurately classify BOT and OC. Our goal is to derive a simple predictive model which also carries a good performance. Using our approach, we obtained a model that consists of just two biomarkers, HE4 and CEA. The model is simple to interpret and outperforms the existing OC prediction methods. It demonstrates that the machine learning approach has good potential in predictive modeling for the complex diseases.

Three new diphenyl ether derivatives from the fermentation products of an endophytic fungus Phomopsis fukushii.

Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl ethers derivatives (4-7), were isolated from the fermentation products of an endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1 and 2 showed strong inhibitions with inhibition zone diameters (IZD) of 20.2 ± 2.5 mm and 17.9 ± 2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 ± 1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD 21.9 ± 2.1 mm.

A computational analysis of dynamic, multi-organ inflammatory crosstalk induced by endotoxin in mice.

Bacterial lipopolysaccharide (LPS) induces an acute inflammatory response across multiple organs, primarily via Toll-like receptor 4 (TLR4). We sought to define novel aspects of the complex spatiotemporal dynamics of LPS-induced inflammation using computational modeling, with a special focus on the timing of pathological systemic spillover. An analysis of principal drivers of LPS-induced inflammation in the heart, gut, lung, liver, spleen, and kidney to assess organ-specific dynamics, as well as in the plasma (as an assessment of systemic spillover), was carried out using data on 20 protein-level inflammatory mediators measured over 0-48h in both C57BL/6 and TLR4-null mice. Using a suite of computational techniques, including a time-interval variant of Principal Component Analysis, we confirm key roles for cytokines such as tumor necrosis factor-α and interleukin-17A, define a temporal hierarchy of organ-localized inflammation, and infer the point at which organ-localized inflammation spills over systemically. Thus, by employing a systems biology approach, we obtain a novel perspective on the time- and organ-specific components in the propagation of acute systemic inflammation.

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer.

BACKGROUND: The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer. METHODS: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. RESULTS: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort. CONCLUSIONS: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.

Sphingomonas tabacisoli sp. nov., a member of the genus Sphingomonas, isolated from rhizosphere soil of Nicotiana tabacum L.

A Gram-staining-negative, aerobic, motile and rod-shaped bacterium, designated strain X1-8T, was isolated from rhizosphere soil of Nicotiana tabacum L. collected from the tobacco produce base located in Kunming, south-west PR China. Cells showed oxidase-negative and catalase-positive reactions and were motile by means of peritrichous flagella. Growth occurred at 25-40 °C and pH 6.0-8.0 with optimal growth at 30-35 °C, pH 7.0. The major respiratory lipoquinone was Q-10. C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) were identified as major cellular fatty acids. The profile of polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid, phosphatidylcholine and one unidentified glycolipid. The major polyamine was sym-homospermidine. The genomic DNA G+C content was 66.5 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that X1-8T should be affiliated to the genus Sphingomonasand formed a clade with most closely related species Sphingomonas changbaiensisNBRC 104936T. The results of 16S rRNA gene sequences similarity analysis indicated that X1-8T had the highest similarity with S. changbaiensisNBRC 104936T (98.4 %) and lower than 96.0 % with other species of the genus Sphingomonas. DNA-DNA hybridization data indicated that X1-8T represented a novel genomic species of the genus Sphingomonas. The characteristics determined in the polyphasic taxonomic study indicated that X1-8T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas tabacisoli sp. nov. (type strain X1-8T=KCTC 62032T=CGMCC 1.16275T) is proposed.

Bacillus endozanthoxylicus sp. nov., an endophytic bacterium isolated from Zanthoxylum bungeanum Maxim leaves.

A Gram-stain-positive, rod-shaped, motile bacterium, designated as 1404T, was isolated from leaves of Chinese red pepper (Huajiao) (Zanthoxylum bungeanum Maxim) collected from Gansu, north-west China. Spores were not observed under a range of conditions. Strain 1404T was observed to grow at 15-45 °C and pH 6.0-10.0 and in presence of 0-5 % (w/v) NaCl concentration. The cell wall of strain 1404T was found to contain meso-diaminopimelic acid, and the predominant respiratory quinone was identified as MK-7. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid as well as three unidentified polar lipids. The major fatty acids profile of strain 1404T consisted of iso-C15 : 0 (25.6 %), anteiso-C15 : 0 (18.4 %) and iso-C14 : 0 (12.1 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 1404T was affiliated to the genus Bacillus and was closely related to Bacillusoryzisoli 1DS3-10T, Bacillusbenzoevorans DSM 5391T and Bacilluscirculans DSM 11T with sequence similarity of 98.3, 98.2 and 96.9 %, respectively. The G+C content of the genomic DNA was determined to be 39.4 mol%. DNA-DNA hybridization values indicated that relatedness between strain 1404T and the type strains of closely related species of the genus Bacillus was below 41 %. Therefore, on the basis of the data from the polyphasic taxonomic study presented, strain 1404T represents a novel species of the genus Bacillus, for which the name proposed is Bacillus endozanthoxylicus sp. nov. The type strain is 1404T (=CCTCC AB 2017021T=KCTC 33827T).