GCaMP, one popular type of genetically-encoded Ca2+ indicator, has been associated with various side-effects. Here we unveil the intrinsic problem prevailing over different versions and applications, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (CaV1). GCaMP acts as an impaired apoCaM and Ca2+/CaM, both critical to CaV1, which disrupts Ca2+ dynamics and gene expression. We then design and implement GCaMP-X, by incorporating an extra apoCaM-binding motif, effectively protecting CaV1-dependent excitation–transcription coupling from perturbations. GCaMP-X resolves the problems of detrimental nuclear accumulation, acute and chronic Ca2+ dysregulation, and aberrant transcription signaling and cell morphogenesis, while still demonstrating excellent Ca2+-sensing characteristics partly inherited from GCaMP. In summary, CaM/CaV1 gating and signaling mechanisms are elucidated for GCaMP side-effects, while allowing the development of GCaMP-X to appropriately monitor cytosolic, submembrane or nuclear Ca2+, which is also expected to guide the future design of CaM-based molecular tools.

The sodium storage mechanism of hard carbon, optimization strategies of electrochemical performance, and the scientific challenges towards the commercialization of sodium-ion batteries were systematically summarized and analyzed.

Shape memory effect in polymer materials has attracted considerable attention due to its promising applications in a variety of fields. However, shape memory polymers prepared by conventional strategy suffer from a common problem, in which high strain capacity and excellent shape memory behavior cannot be simultaneously achieved. This study reports a general and synergistic strategy to fabricate high-strain and tough shape memory organohydrogels that feature binary cooperative phase. The phase- transition micro-organogels and elastic hydrogel framework act synergistically to provide excellent thermomechanical performance and shape memory effect. During shape memory process, the organohydrogels exhibit high strain capacity, featuring fully recoverable stretching deformation by up to 2600% and compression by up to 85% beneath a load ≈20 times the organohydrogel's weight. Furthermore, owing to the micro-organogel and hydrogel heterostructures, the interfacial tension derived from heterophases dominates the shape recovery of the organohydrogel material. Simple processing and smart surface patterning of the shape memory behavior and multiple shape memory effects can also be realized. Meanwhile, these organohydrogels are also nonswellable in water and oil, which is important for multimedia applications.

Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.