Notes

Rolling controls sperm navigation as a result of the actual vibrant rheological qualities of the surroundings.
Substrate-bound structures of AAA+ protein translocases reveal a conserved asymmetric spiral staircase architecture wherein a sequential ATP hydrolysis cycle drives hand-over-hand substrate translocation. However, this configuration is unlikely to represent the full conformational landscape of these enzymes, as biochemical studies suggest distinct conformational states depending on the presence or absence of substrate. Here, we used cryo-electron microscopy to determine structures of the Yersinia pestis Lon AAA+ protease in the absence and presence of substrate, uncovering the mechanistic basis for two distinct operational modes. In the absence of substrate, Lon adopts a left-handed, "open" spiral organization with autoinhibited proteolytic active sites. Upon the addition of substrate, Lon undergoes a reorganization to assemble an enzymatically active, right-handed "closed" conformer with active protease sites. These findings define the mechanistic principles underlying the operational plasticity required for processing diverse protein substrates.Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ-generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy.The discovery of giant viruses infecting eukaryotes from diverse ecosystems has revolutionized our understanding of the evolution of viruses and their impact on protist biology, yet knowledge on their replication strategies and transcriptome regulation remains limited. Here, we profile single-cell transcriptomes of the globally distributed microalga Emiliania huxleyi and its specific giant virus during infection. We detected profound heterogeneity in viral transcript levels among individual cells. Clustering single cells based on viral expression profiles enabled reconstruction of the viral transcriptional trajectory. Reordering cells along this path unfolded highly resolved viral genetic programs composed of genes with distinct promoter elements that orchestrate sequential expression. Exploring host transcriptome dynamics across the viral infection states revealed rapid and selective shutdown of protein-encoding nuclear transcripts, while the plastid and mitochondrial transcriptomes persisted into later stages. Single-cell RNA-seq opens a new avenue to unravel the life cycle of giant viruses and their unique hijacking strategies.CRISPR-Cas12a represents an efficient tool for genome editing in addition to the extensively investigated CRISPR-Cas9. However, development of efficient nonviral delivery system for CRISPR-Cas12a remains challenging. Here, we demonstrate a DNA nanoclew (NC)-based carrier for delivery of Cas12a/CRISPR RNA (crRNA) ribonucleoprotein (RNP) toward regulating serum cholesterol levels. The DNA NC could efficiently load the Cas12a/crRNA RNP through complementation between the DNA NC and the crRNA. Addition of a cationic polymer layer condensed the DNA-templated core and allowed further coating of a charge reversal polymer layer, which makes the assembly negatively charged under a physiological pH but reverts to positive charge under an acidic environment. When Pcsk9 was selected as the target gene because of its important role in regulating the level of serum cholesterol, efficient Pcsk9 disruption was observed in vivo (~48%), significantly reducing the expression of PCSK9 and gaining the therapeutic benefit of cholesterol control (~45% of cholesterol reduction).Functional coating materials have found broad technological applications in diverse fields. Despite recent advances, few coating materials simultaneously achieve robustness and substrate independence while still retaining the capacity for genetically encodable functionalities. MitoSOX Red purchase Here, we report Escherichia coli biofilm-inspired protein nanofiber coatings that simultaneously exhibit substrate independence, resistance to organic solvents, and programmable functionalities. The intrinsic surface adherence of CsgA amyloid proteins, along with a benign solution-based fabrication approach, facilitates forming nanofiber coatings on virtually any surface with varied compositions, sizes, shapes, and structures. In addition, the typical amyloid structures endow the nanofiber coatings with outstanding robustness. On the basis of their genetically engineerable functionality, our nanofiber coatings can also seamlessly participate in functionalization processes, including gold enhancement, diverse protein conjugations, and DNA binding, thus enabling a variety of proof-of-concept applications, including electronic devices, enzyme immobilization, and microfluidic bacterial sensors. We envision that our coatings can drive advances in electronics, biocatalysis, particle engineering, and biomedicine.Explosive energy conversion materials with extremely rapid response times have broad and growing applications in energy, medical, defense, and mining areas. Research into the underlying mechanisms and the search for new candidate materials in this field are so limited that environment-unfriendly Pb(Zr,Ti)O3 still dominates after half a century. Here, we report the discovery of a previously undiscovered, lead-free (Ag0.935K0.065)NbO3 material, which possesses a record-high energy storage density of 5.401 J/g, enabling a pulse current ~ 22 A within 1.8 microseconds. It also exhibits excellent temperature stability up to 150°C. Various in situ experimental and theoretical investigations reveal the mechanism underlying this explosive energy conversion can be attributed to a pressure-induced octahedral tilt change from a - a - c + to a - a - c -/a - a - c +, in accordance with an irreversible pressure-driven ferroelectric-antiferroelectric phase transition. This work provides a high performance alternative to Pb(Zr,Ti)O3 and also guidance for the further development of new materials and devices for explosive energy conversion.
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