Shantou University

As multiple imaging modalities cannot reliably diagnose cardiac tumors, the molecular approach offers alternative ways to detect rare ones. One such molecular approach is CRISPR-based diagnostics (CRISPR-Dx). CRISPR-Dx enables visual readout, portable diagnostics, and rapid and multiplex detection of nucleic acids such as microRNA (miRNA). Dysregulation of miRNA expressions has been associated with cardiac tumors such as atrial myxoma and angiosarcoma. Diverse CRISPR-Dx systems have been developed to detect miRNA in recent years. These CRISPR-Dx systems are generally classified into four classes, depending on the Cas proteins used (Cas9, Cas12, Cas13, or Cas12f). CRISPR/Cas systems are integrated with various isothermal amplifications to detect low-abundance miRNAs. Amplification-free CRISPR-Dx systems have also been recently developed to detect miRNA directly. Herein, we critically discuss the advances, pitfalls, and future perspectives for these CRISPR-Dx systems in detecting miRNA, focusing on the diagnosis and prognosis of cardiac tumors.

Organic photothermal agents (PTAs) with high-performance near-infrared properties hold great promise for precision phototherapy and bioimaging. The development of efficient PTAs depends mainly on advancements in molecular synthesis. However, synthetic approaches for organic PTAs typically involve tedious processes and the consumption of noble metal catalysts, which could leave residues affecting the products' biosafety. In the past few years, a handful of charge transfer complex (CTC) PTAs have been reported. Unfortunately, typical CTCs disintegrate into their donor and acceptor components in water because of their stronger hydrogen bonds with water. To address this issue, facile and synthesis-free super-stable interfacial charge-transfer nanocrystals (H-CTC NPs) have been reported for increasing immunogenic cell death and efficient photoimmunotherapy against tumor recurrence. Water-dispersible H-CTC NPs between pyrene-4,5,9,10-tetrone (PT, acceptor) and indolo[2,3-alpha]carbazole (IC, donor) were prepared with strong intermolecular hydrogen bonds. With this approach, H-CTC NPs are the first examples of stable CTC NPs in water, achieving record-high stability with preferable photothermal conversion efficiency. H-CTC NPs typically cause immunogenic cell death (ICD) and photothermal tumor ablation in vivo. Moreover, distal recurrent tumors are inhibited through the immune synergism between ICD and immune checkpoint therapy. This work developed superstable CTC nanocrystals and explored new pathways for high-performance photoimmunotherapy against recurrent tumors.

In view of climate change and human activities, ocean acidity extreme (OAX) events have been increasingly reported worldwide over the last decades, which possibly retard the growth and development of marine organisms, particularly at their early life-history stages (e.g., embryos or larvae). Thus, understanding whether they can adjust to the sudden increase in seawater acidity has drawn growing attention. Using a commercially and ecologically important bivalve species (Ruditapes philippinarum) with a widespread distribution in the world, we assessed the impact of OAX on its embryonic and larval development as well as expressions of functional genes and lipids to indicate physiological and cellular performance. We found that embryonic development and larval shell formation were inhibited by OAX mainly due to the downregulation of key genes responsible for the uptake of calcium ions from ambient seawater (e.g., NCX, VGCC and SERCA) and the reduced production of bicarbonate ions through the catalytic action of carbonic anhydrase. In addition, a major remodelling in membrane lipids (e.g., PC, PE, PG, PI and PS) indicated that OAX impacted the fluidity and stability of cell membrane, hindering the uptake of calcification substrates. The depletion in energy reserves, such as triacylglycerol, can also account for the impairment in larval shell formation under OAX conditions. By integrating transcriptomics and lipidomics, our findings illustrate a novel molecular mechanism underlying the detrimental effect of OAX on larval development and hence population maintenance of marine organisms, which can have profound implications for sustaining ecosystem stability and aquaculture management.