Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis

Introduction: Bladder cancer (BLCA) is one of the most common malignancies in the urinary system with a poor prognosis and high treatment costs. Identifying potential prognostic biomarkers is significant for exploring new therapeutic and predictive targets of BLCA.Methods: In this study, we screened differentially expressed genes using the GSE37815 dataset. We then performed a weighted gene co‐expression network analysis (WGCNA) to identify the genes correlated with the histologic grade and T stage of BLCA using the GSE32548 dataset. Subsequently, Kaplan Meier survival analysis and Cox regression were used to further identify prognosis‐related hub genes using the datasets GSE13507 and TCGA‐BLCA. Moreover, we detected the expression of the hub genes in 35 paired samples, including BLCA and paracancerous tissue, from the Shantou Central Hospital by qRT‐polymerase chain reaction.Results: This study showed that Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. High expression of ANLN and ASPM was associated with poor overall survival.The qRT‐PCR results revealed that ANLN and ASPM genes were upregulated in BLCA, and there was a correlation between the expression of ANLN and ASPM in cancer tissues and paracancerous tissue. Additionally, the increasing multiples in the ANLN gene was obvious in high-grade BLCA.Discussion: In summary, this preliminary exploration indicated a correlation between ANLN and ASPM expression. These two genes, serving as the risk factors for BLCA progression, might be promising targets to improve the occurrence and progression of BLCA

Experimental research on the jet-breaking characteristics and hydraulic performance of a novel automatic rotating sprinkler

To improve the performance of sprinklers that work under low pressure, a new type of automatic rotating sprinkler equipped with different water dispersion devices was designed and the jet diffusion angle and hydraulic performance of the new and original sprinklers were compared using experimental methods. The results indicate that, when the working pressure is below 200 kPa, the jet diffusion angle of the new sprinkler with the water dispersion device B is the largest. Although the pattern radius of the new sprinkler is slightly lower than that of the original, it is more effective in improving the combined coefficient of uniformity (CU) at lower working pressures. Specifically, when the working pressure was 100 kPa, the new sprinkler with the water dispersion device B, which has a square inner hole with a side length of 6.2 mm, improved the CU by 54.89% on average. Remarkably, the CU of the new sprinkler with water dispersion device B at a working pressure of 100 kPa was 6.65% higher than that of the original sprinkler at a working pressure of 200 kPa. The research results provide valuable insights into the design of sprinklers to improve the performance of low-pressure sprinkler irrigation systems. HIGHLIGHTS A novel automatic rotating sprinkler (NARS) with a water dispersion device has been successfully developed.; The lower the working pressure, the more pronounced the effect of the NARS on improving the overlapped water application uniformity.; The NARS with water dispersion device B ensures that the water application rates within a local area are consistent.

Study on Share Rate of Support Structure for Super-Large Span Twin Tunnels with Small Interval

Super-large span twin tunnels, which can relieve traffic burden and improve the efficiency of roads, have been rapidly popularized in urban construction. Hence, it is very important to master the share rate of support structure in this sort of tunnel correctly. In this paper, some field monitoring and numerical simulation work has been carried out in such a tunnel in Daling, China. The content of field monitoring consisted of the vault settlement, stress of the concrete, and the sum pressure. Firstly, the calculation formula of rock pressure in this kind of tunnel had been deduced, which was based on the theoretical sliding failure mode. Then, the calculated rock pressure was applied to the load structure model step by step with 10% intervals (10%, 20%, …). By comparing the monitoring and the simulation results on vault settlement, the share rate of the primary support was ensured to be 40%. Similarly, by comparing the result on safety factors, the share rate of the secondary lining was obtained (40%). The remained load was born mainly by the surrounding rock itself and the advanced support. Finally, the reliability of the results were verified by the sum pressure. This paper can provide reference for the effective design of support structure in super-large span twin tunnels

Use the predictive models to explore the key factors affecting phytoplankton succession in Lake Erhai, China

Increasing algae in Lake Erhai has resulted in frequent blooms that have not only led to water ecosystem degeneration but also seriously influenced the quality of the water supply and caused extensive damage to the local people, as the lake is a water resource for Dali City. Exploring the key factors affecting phytoplankton succession and developing predictive models with easily detectable parameters for phytoplankton have been proven to be practical ways to improve water quality. To this end, a systematic survey focused on phytoplankton succession was conducted over 2 years in Lake Erhai. The data from the first study year were used to develop predictive models, and the data from the second year were used for model verification. The seasonal succession of phytoplankton in Lake Erhai was obvious. The dominant groups were Cyanobacteria in the summer, Chlorophyta in the autumn and Bacillariophyta in the winter. The developments and verification of predictive models indicated that compared to phytoplankton biomass, phytoplankton density is more effective for estimating phytoplankton variation in Lake Erhai. CCA (canonical correlation analysis) indicated that TN (total nitrogen), TP (total phosphorus), DO (dissolved oxygen), SD (Secchi depth), Cond (conductivity), T (water temperature), and ORP (oxidation reduction potential) had significant influences (p &lt; 0.05) on the phytoplankton community. The CCA of the dominant species found that Microcystis was significantly influenced by T. The dominant Chlorophyta, Psephonema aenigmaticum and Mougeotia, were significantly influenced by TN. All results indicated that TN and T were the two key factors driving phytoplankton succession in Lake Erhai.</p

Safety Analysis of Lining Structure Influenced by Blasting of Tunnel with Extralarge Section and Small Space

In order to ensure the safety of the Daling tunnel with extralarge section and small space, the three-dimensional model of blasting dynamic simulation had been established and verified. Then, the model was used to analyze the influence of the surrounding rock characteristics and blasting design parameters on the blasting vibration of the first hole, and the analysis of the sensitivity of each factor was carried out. The results showed that blasting of the second hole had a serious impact on the safety of the first hole lining structure. Based on the safety threshold and analysis of sensitivity, the explosive velocity, charge density, and digging length were selected as the key parameters affecting the safety of the tunnel structure. Meanwhile, the corresponding engineering measure was taken based on the results of sensitivity and the actual situation on site, and, after that, the maximum PPV of the right wall of the first hole had been reduced to 9.3 cm/s, which effectively guaranteed the safe construction of the tunnel

PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study

Abstract Objective To evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients. Methods 115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX. Results 68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043–1.725]) and 1.401(95%CI [1.013–1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633–0.893]) and 0.734(95%CI [0.570–0.899]) (DeLong’s test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making. Conclusion Evaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management. Trial registration Chinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/ ), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14

A HER2‐targeted Antibody‐Drug Conjugate, RC48‐ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer

Abstract More than half of non‐muscle‐invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder‐preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2‐targeted antibody‐drug conjugate, RC48‐ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48‐ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48‐ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase‐dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48‐ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate‐buffered saline control. The potential toxicity of intravesical RC48‐ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48‐ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48‐ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48‐ADC in NMIBC patients

Microcystis aeruginosa/Pseudomonas pseudoalcaligenes interaction effects on off-flavors in algae/bacteria co-culture system under different temperatures

We conducted an experiment to study the interaction effects of Microcystis aeruginosa and Pseudomonas pseudoalcaligenes on off-flavors in an algae/bacteria co-culture system at three temperatures (24, 28 and 32 degrees C). Gas chromatography mass spectrometry was applied to measure off-flavor compounds dimethyl sulfide (DMS), dimethyl trisulfide (DMTS), 2-methylisobomeol, geosmin (GEO) and beta-cyclocitral. During the lag phase of co-cultured M. aeruginosa (first 15 days), P. pseudoalcaligenes significantly increased the production of DMS, DMTS and beta-cyclocitral at all three temperatures. In the exponential phase of co-cultured M. aeruginosa (after 15 days), M. aeruginosa became the main factor on off-flavors in the co-culture system, and beta-cyclocitral turned to the highest off-flavor compound. These results also indicated that DMS, DMTS and beta-cyclocitral were the main off-flavor compounds in our M. aeruginosa/P. pseudoalcaligenes co-culture system. Univariate analysis was applied to investigate the effects of M. aeruginosa and P. pseudoalcaligenes on the production of off-flavors. The results demonstrated that both M. aeruginosa and P. pseudoalcaligenes could increase the production of DMS and DMTS, while beta-cyclocitral was mainly determined by M. aeruginosa. Our results also provide some insights into understanding the relationship between cyanobacteria and heterotrophic bacteria. (C) 2015 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V