Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system. Here we systematically analyse known degrons and propose a tripartite model comprising the following: (1) a primary degron (peptide motif) that specifies substrate recognition by cognate E3 ubiquitin ligases, (2) secondary site(s) comprising a single or multiple neighbouring ubiquitinated lysine(s) and (3) a structurally disordered segment that initiates substrate unfolding at the 26S proteasome. Primary degron sequences are conserved among orthologues and occur in structurally disordered regions that undergo E3-induced folding-on-binding. Posttranslational modifications can switch primary degrons into E3-binding-competent states, thereby integrating degradation with signalling pathways. Degradation-linked lysines tend to be located within disordered segments that also initiate substrate degradation by effective proteasomal engagement. Many characterized mutations and alternative isoforms with abrogated degron components are implicated in disease. These effects result from increased protein stability and interactome rewiring. The distributed nature of degrons ensures regulation, specificity and combinatorial control of degradation.

In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [¹⁸F]DCFPyL (PYLARIFY^®, Lantheus Holdings), [¹⁸F]rhPSMA-7.3 (POSLUMA^®, Blue Earth Diagnostics) and [⁶⁸Ga]Ga-PSMA-11 (Locametz^®, Novartis/ ILLUCCIX^®, Telix Pharmaceuticals), as well as PSMA-targeted radiotherapeutic agents, such as [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®, Novartis). Concurrently, ligand-drug and immune therapies designed to target PSMA are being advanced through rigorous preclinical research and clinical trials. This review delves into the annals of PSMA-targeted radiotheranostics, exploring its historical evolution as a signature molecule in PCa management. We scrutinise its clinical ramifications, acknowledge its limitations, and peer into the avenues that need further exploration. In the crucible of scientific inquiry, we aim to illuminate the path toward a future where the enigma of PCa is deciphered and where its menace is met with precise and effective countermeasures. In the following sections, we discuss the intriguing terrain of PCa radiotheranostics through the lens of PSMA, with the fervent hope of advancing our understanding and enhancing clinical practice.

Fungal pathogens such as Candida albicans have significant impacts on women’s health and the economy worldwide. Current detection methods often require access to laboratory facilities that are costly, inconvenient, and slow to access. This often leads to self-diagnosis, self-treatment and eventual antifungal resistance. We have created a rapid (within five minutes), cost-effective, and user-friendly method for the early detection of Candida albicans. Our platform utilises aptamer-tagged-gold-core-shell nanoparticles for Candida albicans detection based on the presence of 1,3-β-d glucan molecules. Nanoparticle aggregation occurs in the presence of Candida albicans fungal cells, causing a redshift in the UV-visible absorbance, turning from pink/purple to blue. This colour change is perceptible by the naked eye and provides a “yes”/“no” result. Our platform was also capable of detecting Candida albicans from individual yeast colonies without prior sample processing, dilution or purification. Candida albicans yeast cells were detected with our platform at concentrations as low as 5 × 10⁵ cells within a 50 μL sample volume. We believe that this technology has the potential to revolutionise women’s health, enabling women to test for Candida albicans accurately and reliably from home. This approach would be advantageous within remote or developing areas.

Molecular diagnostics have become indispensable in healthcare, agriculture, and environmental monitoring. This diagnostic form can offer rapid and precise identification of pathogens and biomarkers. However, traditional laboratory-based molecular testing methods can be expensive and require specialised training, limiting their accessibility in resource-limited settings and on-site applications. To overcome these challenges, this study proposes an innovative approach to reducing costs and complexity in portable colorimetric loop-mediated isothermal amplification (LAMP) devices. The research evaluates different resistive heating systems to create an energy-efficient, cost-effective, and compact device to heat a polydimethylsiloxane (PDMS) block for precise temperature control during LAMP reactions. By combining this novel heating system with an off-the-shelf red-green-blue (RGB) sensor to detect and quantify colour changes, the integrated system can accurately detect Leifsonia xyli subsp. xyli, the bacteria responsible for ratoon stunting disease (RSD) in sugarcane. The experimental validation of this system demonstrates its ability to detect the target pathogen in real time, making it an important development for low cost, portable, and easy-to-use molecular diagnostics in healthcare, agriculture, and environmental monitoring applications.