Shuffling the yeast genome using CRISPR/Cas9-generated DSBs that target the transposable Ty1 elements.

Although homologous recombination between transposable elements can drive genomic evolution in yeast by facilitating chromosomal rearrangements, the details of the underlying mechanisms are not fully clarified. In the genome of the yeast Saccharomyces cerevisiae, the most common class of transposon is the retrotransposon Ty1. Here, we explored how Cas9-induced double-strand breaks (DSBs) directed to Ty1 elements produce genomic alterations in this yeast species. Following Cas9 induction, we observed a significant elevation of chromosome rearrangements such as deletions, duplications and translocations. In addition, we found elevated rates of mitotic recombination, resulting in loss of heterozygosity. Using Southern analysis coupled with short- and long-read DNA sequencing, we revealed important features of recombination induced in retrotransposons. Almost all of the chromosomal rearrangements reflect the repair of DSBs at Ty1 elements by non-allelic homologous recombination; clustered Ty elements were hotspots for chromosome rearrangements. In contrast, a large proportion (about three-fourths) of the allelic mitotic recombination events have breakpoints in unique sequences. Our analysis suggests that some of the latter events reflect extensive processing of the broken ends produced in the Ty element that extend into unique sequences resulting in break-induced replication. Finally, we found that haploid and diploid strain have different preferences for the pathways used to repair double-stranded DNA breaks. Our findings demonstrate the importance of DNA lesions in retrotransposons in driving genome evolution.

Characterization and Genomic Analysis of Affinirhizobium gouqiense sp. nov. Isolated from Seawater of Gouqi Island Located in the East China Sea and Reclassification of Rhizobium lemnae to the Genus Affinirhizobium as Affinirhizobium lemnae comb. nov.

A novel bacterium designated as SSA5.23T was isolated from seawater. Cells of SSA5.23T are Gram-stain-negative, short, rod-shaped, and exhibit motility via numerous peritrichous flagella. The strain could grow at temperatures ranging from 15 to 35 °C (optimum at 25 °C), in a salinity range of 0-5.0% (w/v) NaCl, and within a pH range of 6.0-9.0 (optimum at pH 7.0). The predominant cellular fatty acid of SSA5.23T was C18:1 ω7c/C18:1 ω6c, and the major respiratory quinones were Q-9 and Q-10. Diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol were identified as the primary polar lipids. The complete genome (5.47 Mb) of SSA5.23T comprises of a circular chromosome of 3.64 Mb and three plasmids, specifically sized at 59.73 kb, 227.82 kb, and 1.54 Mb, respectively. Certain genes located on the plasmids play roles in denitrification, oxidative stress resistance, and osmotic tolerance, which likely contribute to the adaptability of this strain in marine conditions. Core-proteome average amino acid identity analysis effectively identified the strain's affiliation with the genus Affinirhizobium, showing the highest value (89.9%) with Affinirhizobium pseudoryzae DSM 19479T. This classification was further supported by the phylogenetic analysis of concatenated alignment of 170 single-copy orthologous proteins. When compared to related reference strains, SSA5.23T displayed an average nucleotide identity ranging from 74.9 to 80.3% and digital DNA-DNA hybridization values ranging from 19.9 to 23.9%. Our findings confirmed that strain SSA5.23T represents a novel species of the genus Affinirhizobium, for which the name Affinirhizobium gouqiense sp. nov. (type strain SSA5.23T = LMG 32560T = MCCC 1K07165T) was suggested.

Shinella sedimenti sp. nov., isolated from sediment of Zhairuo Island located in the East China Sea.

A Gram-negative, rod-shaped and aerobic bacterial strain B3.7T, was isolated from the sediment of Zhairuo Island, Zhoushan city, Zhejiang Province, PR China. Maximum growth of strain B3.7T was observed at 30 °C when cultured in a medium containing 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain B3.7T belonged to the genus Shinella; it showed the highest sequence similarity of 98.47 % to Shinella kummerowiae CCBAU 25048T. The average nucleotide identity and digital DNA-DNA hybridization values between strain B3.7T and its reference strains were 82.9-84.2 % and 26.1-27.3 %, respectively. Chemotaxonomic analysis indicated that the sole respiratory quinone was Q-10 and the predominant cellular fatty acids were C19 : 0 cyclo ω8c, C16 : 0, C18 : 1 ω7c 11-methyl and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified phospholipids and two unidentified aminolipids. Collectively, strain B3.7T can be considered to represent a novel species, for which the name Shinella sedimenti sp. nov. is proposed. The type strain is B3.7T (=MCCC 1K07163T=LMG 32559T).

Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells.

Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain of Saccharomyces cerevisiae by whole-genome sequencing of many independent isolates (n = 93) subcloned about 100 times in unstressed growth conditions. The most common alterations were point mutations and small (<100 bp) insertion/deletions (n = 1,337) and mitotic recombination events (n = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually less than 15 kb) and terminal events (mostly cross-overs) in which the LOH tract extends to the end of the chromosome. These two types of LOH events had different distributions, suggesting that they may have initiated by different mechanisms. Based on our results, we present a method of calculating the probability of an LOH event for individual SNPs located throughout the genome. We also identified several hotspots for chromosomal rearrangements (large deletions and duplications). Our results provide insights into the relative importance of different types of genetic alterations produced during vegetative growth.

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae.

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism Saccharomyces cerevisiae facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in S. cerevisiae. Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various S. cerevisiae strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes.

Diagnostic and Predictive Values of Inflammatory Factors in Pathology and Survival of Patients Undergoing Total Cystectomy.

BACKGROUND: Inflammation and tumorigenesis are related. We conducted this study to evaluate whether inflammatory factors (IFs) have a diagnostic value for pathology and a predictive value for survival and recurrence in bladder cancer patients undergoing total cystectomy. METHODS: The patients who were diagnosed with bladder cancer and underwent total cystectomy in our center from 2014 to 2020 were enrolled. The values of neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and systemic immune-inflammation index (SII) were calculated by blood routine test results before operation. The AUC of ROC was calculated to judge the diagnostic value of the IFs in pathology and their corresponding cut-off values. For overall survival (OS) and recurrence-free survival (RFS), the above IFs were grouped according to the cut-off value. The differences between different groups were analyzed by the Kaplan-Meier curves, and the predictive value of these IFs was determined by the Cox proportional hazards regression model. RESULTS: A total of 79 patients were enrolled. All IFs had no diagnostic value for the pathological grade, tumor T stage, and systemic metastasis. Only NLR (AUC = 0.706, cut-off value = 3.12, sensitivity = 75.00%, specificity = 70.00%, P = 0.014), dNLR (AUC = 0.700, cut-off value = 2.49, sensitivity = 66.67%, specificity = 76.67%, P = 0.015), and SII (AUC = 0.704, cut-off value = 463.56, sensitivity = 100.00%, specificity = 40.00%, P = 0.004) had a diagnostic value for lymph node metastasis. The median follow-up time was 31 months, and there was no significant difference in OS between the two groups for all IFs. For RFS, Kaplan-Meier suggested PLR might be predictive when the cut-off value was 266.70 (P = 0.044), but the subsequent Cox proportional hazards regression analysis showed that all IFs had no predictive value for OS and RFS. CONCLUSIONS: We found that in patients undergoing total cystectomy preoperative NLR, dNLR and SII had a diagnostic value for lymph node metastasis, while all these five IFs had no predictive value for OS and RFS. However, this conclusion needs to be further verified by large-scale studies in the future.

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

FedCut: A Spectral Analysis Framework for Reliable Detection of Byzantine Colluders.

This paper proposes a general spectral analysis framework that thwarts a security risk in federated Learning caused by groups of malicious Byzantine attackers or colluders, who conspire to upload vicious model updates to severely debase global model performances. The proposed framework delineates the strong consistency and temporal coherence between Byzantine colluders' model updates from a spectral analysis lens, and, formulates the detection of Byzantine misbehaviours as a community detection problem in weighted graphs. The modified normalized graph cut is then utilized to discern attackers from benign participants. Moreover, the Spectral heuristics is adopted to make the detection robust against various attacks. The proposed Byzantine colluder resilient method, i.e., FedCut, is guaranteed to converge with bounded errors. Extensive experimental results under a variety of settings justify the superiority of FedCut, which demonstrates extremely robust model accuracy (MA) under various attacks. It was shown that FedCut's averaged MA is 2.1% to 16.5% better than that of the state of the art Byzantine-resilient methods. In terms of the worst-case model accuracy (MA), FedCut is 17.6% to 69.5% better than these methods.

PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer.

Background: Cisplatin (DDP) based combination chemotherapy is a vital method for the treatment of bladder cancer (BLca). Chemoresistance easily occurs in the course of cisplatin chemotherapy, which is one of the important reasons for the unfavorable prognosis of BLca patients. Circular RNAs (circRNAs) are widely recognized for their role in the development and advancement of BLca. Nevertheless, the precise role of circRNAs in DDP resistance for BLca remains unclear. Methods: To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. RT-qPCR assay was utilized to assess the expression levels of circRNA, miRNA and mRNA in BLca tissues and cells. Functional experiments were conducted to assess the function of circATIC in BLca progression and chemosensitivity in vitro. Various techniques such as FISH, Dual-luciferase reporter assay, TRAP, RNA digestion assay, RIP and ChIRP assay were used to investigate the relationships between PTBP1, circATIC, miR-1247-5p and RCC2. Orthotopic bladder cancer model, xenograft subcutaneous tumor model and xenograft lung metastasis tumor model were performed to indicate the function and mechanism of circATIC in BLca progression and chemosensitivity in vivo. Results: In our study, we observed that circATIC expression was significantly enhanced in BLca tissues and cells and DDP resistant cells. Patients with higher circATIC expression have larger tumor diameter, higher incidence of postoperative metastasis and lower overall survival rate. Further experiments showed that circATIC accelerated BLca cell growth and metastasis and induced DDP resistance. Mechanistically, alternative splicing enzyme PTBP1 mediated the synthesis of circATIC. circATIC could enhance RCC2 mRNA stability via sponging miR-1247-5p or constructing a circATIC/LIN28A/RCC2 RNA-protein ternary complex. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Conclusion: Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.

Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells.

(1) Background: CREB-binding protein (CBP) is a key transcriptional coactivator of androgen receptors (AR). We conducted this study to investigate the effects of CBP on AR expression and proliferation in benign prostatic hyperplasia (BPH) prostate epithelial cells. (2) Methods: By analyzing a published data set, we found that CBP was closely related to the gene expression of AR in prostate cells. We enrolled 20 BPH patients who underwent transurethral resection of the prostate (TURP) in Peking University First Hospital in 2022, and analyzed the expressions of CBP and AR in BPH prostate tissues. Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells. We also studied the interaction between CBP and AR through a co-immunoprecipitation assay. (3) Results: CBP is consistent with AR in expression intensity in prostate tissues. Inhibiting CBP decreases AR expression, and induces proliferation inhibition, apoptosis, and cell cycle arrest in BPH prostate epithelial cells. The co-immunoprecipitation assay showed that CBP binds with AR to form transcription complexes in prostate epithelial cells. (4) Conclusions: Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer.

Immune checkpoint inhibitors (ICIs) target the negative regulatory pathway of T cells and effectively reactive the anti-tumor immune function of T cells by blocking the key pathway of the immune escape mechanism of the tumor-PD-1/PD-L1, and fundamentally changing the prospect of immunotherapy for non-small cell lung cancer patients. However, such promising immunotherapy is overshadowed by Hyperprogressive Disease, a response pattern associated with unwanted accelerated tumor growth and characterized by poor prognosis in a fraction of treated patients. This review comprehensively provides an overview of Hyperprogressive Disease in immune checkpoint inhibitor-based immunotherapy for non-small cell lung cancer including its definition, biomarkers, mechanisms, and treatment. A better understanding of the black side of immune checkpoint inhibitors therapy will provide a more profound insight into the pros and cons of immunotherapy.

Nonlethal Furfural Exposure Causes Genomic Alterations and Adaptability Evolution in Saccharomyces cerevisiae.

Furfural is a major inhibitor found in lignocellulosic hydrolysate, a promising feedstock for the biofermentation industry. In this study, we aimed to investigate the potential impact of this furan-derived chemical on yeast genome integrity and phenotypic evolution by using genetic screening systems and high-throughput analyses. Our results showed that the rates of aneuploidy, chromosomal rearrangements (including large deletions and duplications), and loss of heterozygosity (LOH) increased by 50-fold, 23-fold, and 4-fold, respectively, when yeast cells were cultured in medium containing a nonlethal dose of furfural (0.6 g/L). We observed significantly different ratios of genetic events between untreated and furfural-exposed cells, indicating that furfural exposure induced a unique pattern of genomic instability. Furfural exposure also increased the proportion of CG-to-TA and CG-to-AT base substitutions among point mutations, which was correlated with DNA oxidative damage. Interestingly, although monosomy of chromosomes often results in the slower growth of yeast under spontaneous conditions, we found that monosomic chromosome IX contributed to the enhanced furfural tolerance. Additionally, terminal LOH events on the right arm of chromosome IV, which led to homozygosity of the SSD1 allele, were associated with furfural resistance. This study sheds light on the mechanisms underlying the influence of furfural on yeast genome integrity and adaptability evolution. IMPORTANCE Industrial microorganisms are often exposed to multiple environmental stressors and inhibitors during their application. This study demonstrates that nonlethal concentrations of furfural in the culture medium can significantly induce genome instability in the yeast Saccharomyces cerevisiae. Notably, furfural-exposed yeast cells displayed frequent chromosome aberrations, indicating the potent teratogenicity of this inhibitor. We identified specific genomic alterations, including monosomic chromosome IX and loss of heterozygosity of the right arm of chromosome IV, that confer furfural tolerance to a diploid S. cerevisiae strain. These findings enhance our understanding of how microorganisms evolve and adapt to stressful environments and offer insights for developing strategies to improve their performance in industrial applications.

Evaluation of a lung cancer screening programme attracting a cohort to actively participate in screening: Honghe Lung Cancer Medical Center Programme.

Background: A lung cancer screening project was conducted by attracting active participation to evaluate its feasibility and effectiveness in areas with poor basic medical education. Methods: This project entailed a prospective, single-arm study which was conducted by means of delivering a lecture on lung cancer at the Honghe Lung Cancer Medical Center to attract public attention and attendance from 28 November 2020 to 21 December 2021. A questionnaire comprising 7 high-risk factors was completed by participants to identify high-risk individuals for further chest low-dose computed tomography examination. Non calcified nodules with a diameter ≥5 mm were deemed positive nodules. The positive nodules were discussed by a multidisciplinary team and treatment suggestions were given. Finally, we analyzed participant information, examination adherence, lung cancer detection rate, and staging. Results: A total of 6,121 individuals were attracted to the project, and 5,925 (96.8%) agreed to participate. Of these, 5,889 (99.4%) completed the survey, with 4,627 (78.6%) in the high-risk group and 1,262 (21.4%) in the non-high-risk group. The proportion of males in the high-risk group was higher than that in the non-high-risk group, and the difference was statistically significant among those aged 40-49 years, 50-59, years and 60-69 years; P<0.01. In the high-risk population, 4,536 (98.0%) of participants adhered to examination, among whom 2,007 (44.2%) with positive nodules, 1,220 (26.9%) with negative nodules, and 1,309 (28.9%) without nodules showed statistical differences in age; P<0.01. The detection rate of lung cancer was 2.2% (99/4,536); 94.0% (93/99) of whom were stage 0-I patients. Conclusions: A health lecture-based approach to improving public participation in regions with poor health education is likely to be effective in promoting the early detection of lung cancer.

The compound AST-003 could effectively promote apoptosis of renal cell carcinoma cells in vitro.

BACKGROUND: The toxicity of Sunitinib limits its clinical application. A new compound AST-003 was designed and synthesized based on the structure of Sunitinib, and previous study has confirmed that AST-003 has the same efficacy and less toxicity as Sunitinib. We conducted this study to further verify the effect of AST-003 on renal cell carcinoma (RCC) cells in vitro and its mechanism. METHODS: Five RCC cell lines, A498, 786-0, SW-13, Caki-1 and ACHN, were used. Cells were treated with different concentrations of AST-003, and the effect of AST-003 on cell viability was detected by MTT assay and IC50 was determined. Blank control group and AST-003 group were set to evaluate the effect of AST-003 on cell apoptosis and cell cycle. The effect of AST-003 on cell protein expression was detected by western blot. RESULTS: After treatment with AST-003, the viability of the above five RCC cells was significantly inhibited. The IC50 of AST-003 on A498, 786-0, SW-13, Caki-1 and ACHN were 7.396, 6.592, 3.803, 12.05 and 3.422 µmol/L, respectively. Compared with the blank control group, the apoptotic rates were 52.37% and 13.34% in A498 cells (P<0.001), 59.23% and 6.66% in 786-0 cells (P<0.001), 45.67% and 4.19% in SW13 cells (P<0.001), 51.67% and 2.33% in Caki-1 cells (P<0.001), 55.40% and 5.50% in ACHN cells (P<0.001). Flow cytometry revealed that the proportion of cells in G0/G1 phase was significantly increased and the proportion of cells in S phase was significantly decreased in AST-003 group compared with blank control group, suggesting that AST-003 could block cells in G0/G1 phase. Western blot indicated that AST-003 could induce the up-regulation of the protein expression levels of apoptotic genes Caspase3, Caspase8, Caspase9, Bax and tumor suppressor p53, and inhibit the phosphorylation of STAT3, mTOR, AMPK and ERK, as well as the expression of Bcl-2, MKK, MKKK, c-jun and Ras proteins. CONCLUSIONS: We found that AST-003 could effectively promote the apoptosis of RCC cells in vitro and block the cells in the intercellular phase, and its mechanism was similar to that of Sunitinib, suggesting that AST-003 has the value for further research.

Androgen downregulation of miR-760 promotes prostate cancer cell growth by regulating IL6.

Prostate cancer (PCa) is one of the most common malignancies in Western countries. Studies have shown that androgen contributes to the progression of PCa, but how androgen promotes PCa remains largely unknown. Here, we demonstrated that androgen suppressed the expression of miR-760 depending on the interaction between androgen and androgen receptor (AR). miR-760 was downregulated in prostate cancer tissues compared with normal tissues. Functional experiments showed that miR-760 downregulation promoted the proliferation and growth of LNCaP and 22rv1 cells. In contrast, miR-760 ectopic expression inhibited the proliferation of LNCaP and 22rv1 cells. DNA synthesis was suppressed by miR-760. Mechanistically, miR-760 bound to the 3'UTR of interleukin 6 (IL6 ). A mutation in the binding site disrupted their interaction. In addition, silencing ofIL 6 suppressed the proliferation of LNCaP and 22rv1 cells. IL6 was upregulated in PCa tissues. Our study reveals that androgen downregulates miR-760 to promote the growth of PCa cells by regulating IL6.

Metal-organic framework-based micropipette is a metal ion responsive nanochannel after adsorbing H2S.

Glass micropipettes are easy to fabricate, have excellent flexibility and stable properties. HKUST-1 and MIL-68(In) are in situ grown in the tip of a micropipette to construct porous nanochannels. After absorbing H2S, the MIL-68(In)-based nanochannel shows effective metal ion responsiveness for Hg2+-detection.

The diagnostic and prognostic value of nuclear matrix protein 22 in bladder cancer.

BACKGROUNDS: This study aimed to evaluate the diagnostic and prognostic value of urine nuclear matrix protein 22 (NMP22) for bladder cancer. METHODS: A retrospective analysis was performed on 229 patients with bladder cancer who underwent transurethral resection of bladder tumor between 2015 and 2018 in our hospital. The sensitivity of NMP22 was calculated to evaluate the diagnostic value of NMP22. Logistic regression analyses were applied to investigate the prognostic value of NMP22 for pathologic features in bladder cancer. RESULTS: The sensitivity of NMP22 for the detection of bladder cancer was 28.82%, and the false negative rate was 71.18%. The sensitivity of NMP22 for the detection of low-grade disease and high-grade disease were 11.11% and 38.51%. NMP22 had significantly higher sensitivity for the detection of high-grade bladder cancer (P<0.001). The sensitivity of NMP22 for the detection of Ta, T1 and T2 disease were 20.78%, 50.85% and 25.00% respectively (Ta refers to noninvasive papillary carcinoma, T1 refers to tumor invades subepithelial connective tissue, T2 refers to tumor invades muscularis propria). NMP22 had significantly higher sensitivity for detection of T1 disease (P<0.001). Univariate and multivariate logistic regression analysis suggested NMP22 might be an independent prognostic factor for high-grade (P<0.001) and T1 disease (P<0.001) in patients with bladder cancer. CONCLUSIONS: Although the sensitivity of NMP22 was significantly higher in the detection of T1 and high-grade bladder cancer, the false negative rate was high. Besides, the NMP22 might be a prognostic factor for high-grade and T1 bladder cancer, but considering the limitations of this study, further studies are needed.

Diagnostic Value of Inflammatory Factors in Pathology of Bladder Cancer Patients.

We conducted this study to evaluate the diagnostic value of Inflammatory Factors (IFs) in the pathology of bladder cancer patients. The patients who were diagnosed with urothelial bladder carcinoma (bladder cancer) and underwent surgical treatment in our center from 2014 to 2019 were enrolled. The values of Neutrophil to Lymphocyte Ratio (NLR), derived Neutrophil to Lymphocyte Ratio (dNLR), Platelet to Lymphocyte Ratio (PLR), Lymphocyte to Monocyte Ratio (LMR), Systemic Immune-inflammation Index (SII), and Prognostic Nutritional Index (PNI) were calculated by blood routine test results before operation. After obtaining the postoperative pathology of the patients, the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) curves was calculated to evaluate the diagnostic value of these IFs in pathology and their corresponding cut-off values. A total of 641 bladder cancer patients were enrolled. The median values of NLR, dNLR, PLR, LMR, SII, and PNI were 6.33, 4.09, 156.47, 2.66, 1114.29, and 51.45, respectively. Grouped patients according to the pathological grade, the NLR, dNLR, PLR, and SII of the high-grade group were significantly higher than those of the low-grade group (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), while the LMR and PNI were significantly lower than those of the low-grade group (P = 0.003 and P < 0.001). Divided patients into non-muscle invasion group (Tis + Ta + T1) and muscle invasion group (T2 + T3 + T4), in which NLR, dNLR, PLR, and SII in the muscle invasion group were significantly higher than those in the non-muscle invasion group (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), while LMR and PNI were significantly lower than those in the low-grade group (P = 0.012 and P < 0.001). ROC curves analyses showed that NLR, dNLR, PLR, LMR, SII, and PNI had predictive value for pathological grade (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively) and muscle invasion (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). The results suggest the higher NLR, dNLR, PLR, SII, and lower LMR and PNI are associated with higher risk of high-grade and muscle invasive disease. However, this conclusion needs to be further clarified in the future.

Heat shock drives genomic instability and phenotypic variations in yeast.

High temperature causes ubiquitous environmental stress to microorganisms, but studies have not fully explained whether and to what extent heat shock would affect genome stability. Hence, this study explored heat-shock-induced genomic alterations in the yeast Saccharomyces cerevisiae. Using genetic screening systems and customized single nucleotide polymorphism (SNP) microarrays, we found that heat shock (52 °C) for several minutes could heighten mitotic recombination by at least one order of magnitude. More than half of heat-shock-induced mitotic recombinations were likely to be initiated by DNA breaks in the S/G2 phase of the cell cycle. Chromosomal aberration, mainly trisomy, was elevated hundreds of times in heat-shock-treated cells than in untreated cells. Distinct chromosomal instability patterns were also observed between heat-treated and carbendazim-treated yeast cells. Finally, we demonstrated that heat shock stimulates fast phenotypic evolutions (such as tolerance to ethanol, vanillin, fluconazole, and tunicamycin) in the yeast population. This study not only provided novel insights into the effect of temperature fluctuations on genomic integrity but also developed a simple protocol to generate an aneuploidy mutant of yeast.

Direct population of triplet excited states through singlet-triplet transition for visible-light excitable organic afterglow.

Invoking efficient afterglow in metal-free organic molecules represents an important material advancement. However, organic afterglow suffers from low intensity and efficiency and generally needs to be excited by UV light owing to its spin-forbidden phosphorescent nature that essentially requires facile intersystem crossing (ISC). Here, we propose a strategy to bypass the traditional ISC through facilitating singlet-triplet transition to directly populate triplet excited states from the ground state by combining synergetic effects of both heavy/hetero-atom incorporation and aromatic aggregation. Verified by systematic experimental and computational investigations, this unique singlet-to-triplet absorption results in a much improved organic afterglow quantum efficiency up to 9.5% with a prolonged lifetime of 0.25 s under visible-light irradiation. Fundamentally, this work illustrates for the first time the great potential of the direct population method to red-shift the excitation wavelength and improve the afterglow efficiency, offering important clues for the development of triplet-state involved organic optoelectronic technologies.