Detecting Pb2+ in aqueous environment and live cells by amphiphilic pillar[5]arene-assembled supramolecular sensor based on host-guest charge transfer mechanism.

Water-soluble fluorescent chemosensors for lead ion are highly desirable in environmental detection and bioimagery. Based on a water-soluble pillar[5]arene WP5 and imidazolium terminal functionalized 2,2'-bibenzimidazole derivative BIHB, we report a host-guest charge transfer assembly BIHB-2WP5 for sensitive and selective detection of Pb2+ in pure aqueous media. As a result of its high electron-rich cavity, WP5 can bind electron-deficiency guest BIHB with various host/guest stoichiometry to easily tune the microtopography of assembly from nanoparticle to nanocube. In view of the good biocompatibility and sensitivity, the supramolecular assembly BIHB-2WP5 was used as a fluorescent probe for the detection of Pb2+ in living cells and a smartphone Pb2+ detection device was constructed for the in situ test.

Molecular classifications of prostate cancer: basis for individualized risk stratification and precision therapy.

Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then guide therapeutic schemes, such as active monitoring, standalone surgical intervention, or surgery supplemented with postoperative adjunctive therapy, thereby circumventing disease exacerbation and excessive treatment. Classifications based on clinicopathological features, such as prostate cancer-specific antigen, Gleason score, and TNM stage, are still the main risk stratification strategies and have played an essential role in standardized clinical decision-making. However, mounting evidence indicates that clinicopathological parameters in isolation fail to adequately capture the heterogeneity exhibited among distinct PCa patients, such as those sharing identical Gleason scores yet experiencing divergent prognoses. As a remedy, molecular classifications have been introduced. Currently, molecular studies have revealed the characteristic genomic alterations, epigenetic modulations, and tumour microenvironment associated with different types of PCa, which provide a chance for urologists to refine the PCa classification. In this context, numerous invaluable molecular classifications have been devised, employing disparate statistical methodologies and algorithmic approaches, encompassing self-organizing map clustering, unsupervised cluster analysis, and multifarious algorithms. Interestingly, the classifier PAM50 was used in a phase-2 multicentre open-label trial, NRG-GU-006, for further validation, which hints at the promise of molecular classification for clinical use. Consequently, this review examines the extant molecular classifications, delineates the prevailing panorama of clinically pertinent molecular signatures, and delves into eight emblematic molecular classifications, dissecting their methodological underpinnings and clinical utility.

Evolution of carbapenem resistance in klebsiella pneumoniae and escherichia coli carrying blaNDM-1 gene: imipenem exposure results in sustained resistance memory of strains in vitro.

BACKGROUND: Antibiotics exert an outstanding selective pressure on bacteria, forcing their chromosomal gene mutations and drug resistance genes to spread. The objective of this study is to evaluate the expression of the New Delhi Metallo-ß-Lactamase-1 gene (blaNDM-1) in the clinical isolate (Klebsiella pneumoniae TH-P12158), transformant strains Escherichia coli BL21 (DE3)-blaNDM-1, and Escherichia coli DH5α- blaNDM-1 when exposed to imipenem. METHODS: ß-Lactamase genes (blaSHV, blaTEM-1, blaCTX-M-9, blaIMP, blaNDM-1, blaKPC, blaOXA, blaGES, and blaDHA) from randomly selected carbapenems-sensitive K.pneumoniae (n = 20) and E.coli (n = 20) strains were amplified by PCR. The recombinant plasmid of pET-28a harboring blaNDM-1 was transformed into E.coli BL21 (DE3) and E.coli DH5α by electroporation. The resistance phenotype and higher blaNDM-1 expression in K.pneumoniae TH-P12158, transformant E.coli BL21 (DE3)-blaNDM-1, and E.coli DH5α-blaNDM-1 were observed when exposed to imipenem with grade increasing, decreasing, and canceling doses, respectively. RESULTS: After being exposed to different doses of imipenem, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of antimicrobial drugs and blaNDM-1 expression of strains increased, which was positively correlated with doses of imipenem. On the contrary, with the decrease or cancellation of imipenem doses, the blaNDM-1 expression was deteriorated, while the MIC and MBC values remained relatively stable. These results demonstrated that low doses of imipenem (˂MIC) could press blaNDM-1 positive strains producing stable drug resistance memory and altered blaNDM-1 expression. CONCLUSIONS: Low doses of imipenem could press blaNDM-1 positive strains producing sustained resistance memory and altered blaNDM-1 expression. In particular, the positive correlation between the resistance genes expression and antibiotics exposure shows promising guiding significance for clinical medication.

Non-coding RNAs: Emerging roles in the characterization of immune microenvironment and immunotherapy of prostate cancer.

Prostate cancer is the most common tumor among men. Although the prognosis for early-stage prostate cancer is good, patients with advanced disease often progress to metastatic castration-resistant prostate cancer (mCRPC), which usually leads to death owing to resistance to existing treatments and lack of long-term effective therapy. In recent years, immunotherapy, especially immune checkpoint inhibitors (ICIs), has made great progress in the treatment of various solid tumors, including prostate cancer. However, the ICIs have only shown modest outcomes in mCRPC compared with other tumors. Previous studies have suggested that the suppressive tumor immune microenvironment (TIME) of prostate cancer leads to poor anti-tumor immune response and tumor resistance to immunotherapy. It has been reported that non-coding RNAs (ncRNAs) are capable of regulating upstream signaling at the transcriptional level, leading to a "cascade of changes" in downstream molecules. As a result, ncRNAs have been identified as an ideal class of molecules for cancer treatment. The discovery of ncRNAs provides a new perspective on TIME regulation in prostate cancer. ncRNAs have been associated with establishing an immunosuppressive microenvironment in prostate cancer through multiple pathways to modulate the immune escape of tumor cells which can promote resistance of prostate cancer to immunotherapy. Targeting these related ncRNAs presents an opportunity to improve the effectiveness of immunotherapy in this patient population.

Macrophages and monocytes mediated activation of oxidative phosphorylation implicated the prognosis and clinical therapeutic strategy of Wilms tumour.

Wilms tumour is the fourth leading cause of paediatric malignancy, but the detailed relationship between the tumour microenvironment and prognosis remains largely unclear. In this research, gene expression profile and clinical information from TARGET and the First Affiliated Hospital of Anhui Medical University were collected. After comparing the prognostic value of the associated immune cells, we established a nomogram to predict the prognosis of Wilms tumour based on monocyte infiltration, macrophage infiltration, stage, and sex. Further results showed that the most significant relationship between matrix metallopeptidase 9 and prognosis or macrophage infiltration. Meanwhile, by gene set enrichment or variation analyses and immunohistochemistry staining, we demonstrated that the most highly enriched hub genes were closely related to the activated oxidative phosphorylation pathway. Finally, through tumour immune dysfunction and an exclusion algorithm, the satisfactory discriminative performance of our nomogram was revealed for predicting the response to clinical therapy. Anti-PD1 therapy is more suitable for Wilms tumour patients with high nomogram points, and chemotherapies are more effective for patients with low nomogram score.

Signature for Prostate Cancer Based on Autophagy-Related Genes and a Nomogram for Quantitative Risk Stratification.

Background: Prostate cancer (PCa) ranks as the most common malignancy and the second leading cause of cancer-related death among males worldwide. The essential role of autophagy in the progression of PCa and treatment resistance has been preliminarily revealed. However, comprehensive molecular elucidations of the correlation between PCa and autophagy are rare. Method: We obtained transcription information and corresponding clinicopathological profiles of PCa patients from TCGA, MSKCC, and GEO datasets. LAASO analysis was employed to select gene signatures and estimate the autophagy score for each patient. Correlations between the signature and prognosis of PCa were investigated by K-M and multivariate Cox regression analyses. A nomogram was established on the basis of the above results. Further validations relied on ROC, calibration analysis, decision curve analysis, and external cohorts. Variable activated signaling pathways were revealed using GSVA algorithms, and the genetic alteration landscape was elucidated via the oncodrive module from the "maftools" R package. In addition, we also examined the therapeutic role of the signature based on phenotype data from GDSC 2016. Result: Six autophagy-related genes were eventually selected to establish the signature, including ULK1, CAPN10, FKBP5, UBE2T, NLRC4, and BNIP3L. We used these genes and corresponding coefficients to calculate an autophagy score (AutS) for each patient in this study. A high AutS group and a low AutS group were divided on the mean AutS of the patients. Longer overall survival, higher Gleason score and PSA, and better response to ADT were observed in patients with high AutS. Meanwhile, we found that high AutS PCa was related to more proliferation-associated signaling activation and higher genetic mutation frequencies, manifesting a poor prognosis. A nomogram was constructed based on GS, T stage, PSA, and AutS as covariates. Its discriminative efficacy and clinical value were validated using robust statistical methods. Finally, we tested its prognostic value through two external cohorts and six published signatures. Conclusion: The autophagy-related gene signature is a highly discriminative model for risk stratification and drug therapy in PCa, and a nomogram incorporating AutS might be a promising tool for precision medicine.

Role of Non-Coding RNA in Neurological Complications Associated With Enterovirus 71.

Enterovirus 71 (EV71) is the main pathogenic virus that causes hand, foot, and mouth disease (HFMD). Studies have reported that EV71-induced infections including aseptic meningitis, acute flaccid paralysis, and even neurogenic pulmonary edema, can progress to severe neurological complications in infants, young children, and the immunosuppressed population. However, the mechanisms through which EV71 causes neurological diseases have not been fully explored. Non-coding RNAs (ncRNAs), are RNAs that do not code for proteins, play a key role in biological processes and disease development associated with EV71. In this review, we summarized recent advances concerning the impacts of ncRNAs on neurological diseases caused by interaction between EV71 and host, revealing the potential role of ncRNAs in pathogenesis, diagnosis and treatment of EV71-induced neurological complications.

Structural and metabolic changes in the traumatically injured rat brain: high-resolution in vivo proton magnetic resonance spectroscopy at 7 T.

PURPOSE: The understanding of microstructural and metabolic changes in the post-traumatic brain injury is the key to brain damage suppression and repair in clinics. METHODS: Ten female Wistar rats were traumatically injured in the brain CA1 region and above the cortex. Next, diffusion tensor magnetic resonance imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) were used to analyze the microstructural and metabolic changes in the brain within the following 2 weeks. RESULTS: Anisotropy fraction (FA) and axial diffusivity (AD) of the corpus callosum (CC) began to decrease significantly at day 1, whereas radial diffusivity (RD) significantly increased immediately after injury, reflecting the loss of white matter integrity. Compared with day 3, RD decreased significantly at day 7, implicating the angioedema reduction. In the hippocampus, FA significantly increased at day 7; the choline-containing compounds (Cho) and myo-inositol (MI) remarkably increased at day 7 compared with those at day 3, indicating the proliferation of astrocytes and radial glial cells after day 7. No significant differences between DTI and 1H MRS parameters were observed between day 1 and day 3. CONCLUSION: Day 1-3 after traumatic brain injury (TBI) may serve as a relatively appropriate time window for treatment planning and the following nerve repair.