Puerarin modulation of CENPA affects downstream PLK1 and CCNB1 expression to inhibit bladder cancer cell proliferation

Background:The treatment alternatives for bladder cancer(BLCA),the 10th most prevalent cancer in the world,need to be further investigated,and many active substances like Puerarin in herbal medicine were found to be effective in treating BLCA.The purpose of this study was to investigate the potential treating mechanisms of Puerarin on BLCA.Methods:The cell counting kit 8 assay and flow cytometry were performed to confirm Puerarin’s ability to suppress BLCA.The differentially expressed proteins(DEPs)were obtained by Tandem Mass Tags technology and functional enrichment analysis performed by R studio.The most enriched pathways were selected for study and the DEPs were screened out.Protein-protein interaction network maps were created using String and Cytoscape and key proteins,which will be analyzed for survival,expression,and upstream transcription factor prediction,were screened out using the cytoHubba plugin.CHEA3 was used to obtain upstream transcription factor validated by molecular docking and western blotting experiments.Results:Cell counting kit 8 showed that Puerarin inhibited BLCA cells,with 50%inhibitory concentration of 218μmol/L in T24 and 198μmol/L in 5637.Flow cytometry reveals that Puerarin blocks T24 and 5637 cells in G1 phase.1,385 DEPs were obtained and the enrichment analysis revealed that cell cycle and DNA replication were the two main areas in which DEPs were enriched.Cyclin-B-cyclin dependent kinase 1(CDK1),cyclin B1(CCNB1),and polo-like kinase 1(PLK1)were identified as key proteins,and their upstream transcription factor was predicted to be centromere protein A(CENPA).Puerarin’s binding energy to CENPA was determined by molecular docking to be−6.3 kcal/mol,indicating a strong binding interaction.Western blot showed that Puerarin significantly reduced the expression of CENPA.Conclusion:We hypothesize that Puerarin may inhibit the proliferation of bladder cancer cells by inhibiting CENPA expression to regulate PLK1 and CCNB1 expression,thereby affecting cell cycle.

Tumor cell plasticity in targeted therapy-induced resistance:mechanisms and new strategies

Despite the success of targeted therapies in cancer treatment,therapy-induced resistance remains a major obstacle to a completecure.Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity.Severalreversible mechanisms have been proposed to circumvent tumor cell plasticity,including epigenetic modifications,regulation oftranscription factors,activation or suppression of key signaling pathways,as well as modification of the tumor environment.Epithelial-to-mesenchymal transition,tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity.Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employcombination treatments.In this review,we delineate the formation of tumor cell plasticity and its manipulation of tumor evasionfrom targeted therapy.We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types oftumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance.New therapeutic strategiessuch as inhibition or reversal of tumor cell plasticity are also presented.We also discuss the multitude of clinical trials that areongoing worldwide with the intention of improving clinical outcomes.These advances provide a direction for developing noveltherapeutic strategies and combination therapy regimens that target tumor cell plasticity.

Understanding stress corrosion cracking behavior of 7085-T7651 aluminum alloy in polluted atmosphere

The electrochemical and Stress Corrosion Cracking(SCC)behaviors of 7085-T7651 aluminum alloy in different environments are studied by electrochemical and mechanical testing.The research shows that the type,concentration of the corrosive medium and electrolyte state affect the electrochemical and SCC controlling processes of aluminum alloys.The Thin Electrolyte Layer(TEL)state and the addition of HSO3–increase the corrosion rate and SCC susceptibility.The presence of HSO3–in a corrosive environment can significantly accelerate the corrosion rate and mechanical property degradation,and this effect increases with the increase of HSO3–concentration.Compared with the solution environment,the TEL environment will further aggravate corrosion and mechanical property degradation.With the increase of HSO3–concentration,the pH of the corrosive environment exhibits little change,while the SCC degradation is significantly promoted.This is attributed to the HSO3–induced buffer effect and film-assisted stress effect,yielding the overshadowing effect against solution pH.

Cultivation, identification and quantification of one species of yeast-like symbiotes, Candida, in the rice brown planthopper, Nilaparvata lugens

The brown planthopper （BPH）, Nilaparvata lugens Stal, which is one of the most destructive pests of rice, has been confirmed to harbor yeast-like symbiotes （YLS） in the fat body. Several morphologically different YLS have been previously isolated and cultured in vitro from BPH, but direct evidence is lacking to further clarify whether the cultured YLS were from BPH. In this study, one species of YLS was successfully cultured in vitro and simultaneously verified to exist in the fat body of BPH by sequence analysis and nested polymerase chain reaction （PCR）. The cultured YLS isolate in vitro was identified as a member of the genus Candida on the basis of 18S rDNA （ribosomal DNA） and 5.8S-ITS （internal transcribed spacer） rDNA sequence and a phylogenetic analysis of ITS sequences from yeast. Therefore, this yeast isolate was named as Candida-like symbiotes. Candida-like symbiotes was found to exist in fat bodies, ovaries and newly laid eggs of the BPH, but not in the heads, thoraxes and mid-guts. In addition, the number of Candida- like symbiotes in 1×106 of purified YLS from BPH fat bodies was speculated to be （5.32±0.22）×104 on the basis of a quantitative PCR analysis.

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment,febuxostat on the gut microbiota

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout.The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment,febuxostat on gut microbiota in gout.16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients,38 gout patients treated with febuxostat,and 26 healthy controls.A restriction of gut microbiota biodiversity was detected in the untreated gout patients,and the alteration was partly restored by febuxostat.Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients.Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism,which was comparatively enhanced in the febuxostat treated gout patients.A classification microbial model obtained a high mean area under the curve up to 0.973.Therefore,gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.

Commentary on “Transurethral seminal vesiculoscopy for recurrent hemospermia: experience from 419 cases”

Dear Editor,We have read the article by Chen et al.1 with great interest.They reported the effect of transurethral seminal vesiculoscopy(TSV)for the treatment of recurrent hemospermia,and they concluded that TSV was an effective and safe procedure in the management of seminal tract disorders.1 TSV is an endoscopic technique that has developed rapidly in recent years.Because it is a relatively simple procedure and does not change the normal anatomical structures of seminal vesicles,this technique is becoming an alternative for the diagnosis and treatment of seminal vesicle and seminal tract diseases.

Corrosion Evolution of High-Strength Aluminum Alloys in the Simulated Service Environment of Amphibious Aircraft in the Presence of Chloride and Bisulfite

The corrosion evolution of 2024-T351 and 7075-T651 aluminum alloys in the thin electrolyte layer(TEL)and wet-dry alternating cycle(WDAC)environment is studied in this work.The results show that in the TEL environment,the competitive effect between H+that accelerates corrosion reactions and deposition of aluminum sulfate that impedes corrosion attacks exists during the corrosion exposure.The difference is that with increasing HSO_(3)^(-),subsurface intergranular corrosion on 2024-T351 is promoted to form exfoliation corrosion eventually and the degree of exfoliation corrosion begins to decrease because the blocking effect of aluminum sulfate exceeds the expediting effect of H+.For 7075-T651,the corrosion area and the corrosion diameter decrease gradually,which is attributed to the HSO_(3)^(-)-enhanced deposition of corrosion products and their blocking effect.In the WDAC environment,the corrosion processes of 2024-T351 and 7075-T651 are the acidic dissolution of the matrix during the soaking phase.When the HSO_(3)^(-)concentration is high enough(0.1 M),the inhibiting effect of aluminum sulfate becomes the dominant factor.