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For many years 3H and 14C labelling of molecules of pharmaceutical interest has been performed to study their in vivo biodistribution on animal tissue sections through β-particles detection. Film autoradiography has progressively been replaced by digital β-imagers capable of high sensitivity, real-time imaging and activity counting for absolute quantification of radioactive compounds in tissue sections. After the discovery of the tumor heterogeneity phenomenon, research efforts for characterizing cell heterogeneity have been at the heart of oncology research, aiming at a better understanding of the causes and progression of the disease. This new perspective has also allowed for cell-targeting drugs, and radically changed both sample sizes and radiotracer activities. In this context, Medica-Plus, a transversal project gathering biologists, microfluidics specialists and detector developers, intends to perform quantification of low dose 3H- or 14C-labelled drugs inside single cells. This article reports preliminary results obtained with a prototype detector measuring tritium-generated signal.

Solid-phase synthesis of phosphinic peptides was introduced 10 years ago. A major application of this chemistry has been the development of potent synthetic inhibitors of zinc metalloproteases. Specific properties of the inhibitors produced in recent years are reviewed, supporting the notion that phosphinic pseudo-peptides are useful tools for studying the structural and functional biology of zinc proteases.

The human somatic angiotensin converting enzyme (ACE) contains two homologous domains, each bearing a zinc-dependent active site. All of the synthetic inhibitors of this enzyme used in clinical applications interact with these two active sites to a similar extent. Recently, several lines of evidence have suggested that the N-terminal active site of ACE might be involved in specific hydrolysis of some important physiological substrates, like Acetyl-Seryl-Aspartyl-Lysyl-Proline, a negative regulator of hematopoietic stem cell differentiation and proliferation. These findings have stimulated studies aimed at identifying new ACE inhibitors able to block only one of the two active sites of this enzyme. By screening phosphinic peptide libraries, we discovered a phosphinic peptide Ac-Asp-(L)Pheψ (PO2-CH2)(L)Ala-Ala-NH2, called RXP 407, which is able to differentiate the two ACE active sites, with a dissociation constant three orders of magnitude lower for the N-domain of the enzyme. The usefulness of a combinatorial chemistry approach to develop new lead structures is underscored by the unusual chemical structure of RXP 407, as compared with classical ACE inhibitors. As a highly potent and selective inhibitor of the N-terminal active site of wild ACE (Ki= 12 nM), RXP 407, which is metabolically stable in vivo may lead to a new generation of ACE inhibitors able to block in vivo only a subset of the different functions regulated by ACE.

To fulfill needs in oncological research a new Micromegas detector has been developed to follow radiolabelled drugs in living organisms at the single cell level. This article describes the proof-of-concept of such a detector and compares its ability to detect and assess sub-becquerel \\tritium~activities with a commercial \\(\\beta\\)-imager

Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy 1 . Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study 2 , 3 . Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis. Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

One-Dimensional (1D) pure-ZnO, Zn 0.9 Mg 0.1 O and Zn 0.8 Mg 0.2 O thin films have been successfully grown over a glass substrate using simple economical chemical bath deposition method (CBD). This investigation explores the enhancement in photocurrent and photosensitivity of Zn 1− x Mg x O thin films via induced defects with vertically aligned hexagonal rod-like array thin films. The structural, optical and electrical properties of the synthesized materials have been elucidated using X-ray Diffraction (XRD), Raman, UV–Vis spectroscopy, Photoluminescence (PL), and I –V characteristics. Hexagonal rod-like morphology has been confirmed from both XRD and SEM results. Change in structural properties revealed that the formation of the Mg(OH) 2 phase for Zn 1− x Mg x O thin films from XRD spectra. Thus, the impact of extra Magnesium (Mg) which is difficult to incorporate in ZnO lattice sites which causes the phase segregation and possibly creates morphological and structural defects. This has been also confirmed from electron–phonon interaction in Raman analysis. Such as the Raman-shift of E2 (high) mode in Zn 1− x Mg x O thin films towards higher frequencies indicates the substitution of Mg at O lattice sites. However the formation of phase segregation had a significant effect on optical as well as electrical properties of the ZnO hexagonal rods thin films. From UV–Vis spectra, the intensity of absorption edges for Mg-doped samples are decreases while the optical band gaps are increases from 2.87 to 3.47 eV and also from PL spectrum shows that the defect states in visible range are increases with increasing Mg content in ZnO. The parameters like photocurrent and electrical resistance are calculated from I – V characteristics and the results shows that the photosensitivity enhanced as Mg content increases in ZnO.

Herein we report, synthesis of non-toxic kesterite Cu 2 ZnSnS 4 (CZTS) nanoflakes thin film by facile, one-step and inexpensive chemical bath deposition method without any post deposition treatment. The kesterite structure of the as-grown CZTS thin film was confirmed by X-ray diffraction pattern (XRD) when compared with standard data (JCPDS #26–0575). In the Raman spectrum two principal peaks at 338 and 286 cm − 1 are clearly identified confirms the formation of kesterite structure of as-grown CZTS. The presence of all desired elements in the film was confirmed by energy dispersive X-ray spectroscopy (EDAX) analysis. Uniform growth of fine nanoflakes distributed over the entire surface of the substrate, oriented along (110) plane are reported here. The estimated crystallite size of the kesterite CZTS nanoflakes thin film was ~ 45 nm. Higher absorption in the visible region was observed in UV absorption spectrum with a band gap value of ~ 1.6 eV. I–V characteristic curve show straight line nature passing through the origin with high current for both in dark and under light illumination. The drastic increase in current after light illumination (150 W) was observed results in 88.5% photosensitivity. Furthermore, the heterojunction using CZTS as an absorber layer and ZnS as a window layer were fabricated on FTO coated glass substrate with ‘Glass Substrate/FTO/ZnS/CZTS/Ag’ device configuration which resulted in 1.71% efficiency.

IntroductionProstate cancer (PCa) is the most common cancer in men. Recurrence may occur in up to half of patients initially treated with curative intent for high-risk localised/locally advanced PCa. Pelvic nodal recurrence is common in this setting, but no clear standard of care exists for these patients, with potential therapeutic approaches including stereotactic body radiotherapy (SBRT) to the involved node(s) alone, extended nodal irradiation (ENI) to treat sites of potential micrometastatic spread in addition to involved node(s) and androgen deprivation therapy with or without additional systemic anticancer therapies. Based on observational studies, ENI is associated with promising metastasis-free survival (MFS) compared with SBRT and appears to result in low rates of severe late toxicity.Methods and analysisPelvis Or Involved Node Treatment: Eradicating Recurrence in Prostate Cancer is a UK multicentre, open-label, phase III randomised controlled trial, which will deliver much needed, high-quality evidence of the impact on metastatic progression from ENI compared with SBRT in patients with PCa pelvic nodal recurrence. The trial will also evaluate the long-term toxicity of 5-fraction ENI compared with a standard 20-fraction schedule. The trail will randomise 480 participants in a ratio of 2:1:1 to SBRT, 5-fraction ENI or 20-fraction ENI from 35 to 40 UK radiotherapy sites over 4 years. Coprimary endpoints are MFS at 3 years and participant-reported late bowel toxicity at 3 years. Secondary endpoints include overall survival, biochemical progression-free survival, failure-free survival, patterns of failure, participant-reported/clinician-reported toxicity and health-related quality of life. Collection of blood and tissue samples will enable future evaluation of biomarkers of disease and toxicity and support stratification of salvage therapeutic approaches.Ethics and disseminationEthical approval was obtained from NHS Health Research Authority, East of England – Cambridgeshire and Hertfordshire Research Ethics Committee (24/EE/0099). Trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines.Trial registration numberISRCTN11089334, registered on 23 September 2024.