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Conventional thrombolytic agents demonstrated limited efficacy in treating thrombotic disorders characterized by narrow therapeutic windows and progressive vascular injury, lacking the required precision, timeliness, and treatment durability. Here an engineered probiotic powered micro‐rod robot for targeted and penetrative treatment for thrombus is developed. This micro‐rod robot (SrEcNPL) using natural probiotics as bio‐carriers, functionalized with thrombolytic carbon nanotubes and platelet membrane‐coated nanoparticles loaded with targeted vasodilators. The robot exploits the rapid movement of probiotics, combined with the active targeting ability of the platelet membrane, to achieve rapid and precise drug delivery to thrombus tissue. Based on the natural rod‐shaped structure of probiotics, SrEcNPL can deeply penetrate thrombus tissue, achieving faster thrombolysis efficiency. The thrombolytic micro‐robot combines thrombus‐targeting capability with prolonged circulation time and controlled vasodilation, maintaining vascular patency and inhibiting secondary thrombus. Results indicate that this micro‐robot can quickly and accurately target and penetrate thrombus tissue, extending the biological half‐life of thrombolytic drugs by ≈332 times and enabling sustained thrombolysis. This novel dual‐pronged combined thrombolytic therapy has significant scientific implications for treating thrombotic diseases with narrow therapeutic windows caused by vascular injury. For thrombotic diseases with narrow therapeutic windows and persistent vascular damage; existing thrombolytic drugs are difficult to achieve precise; timely; and sustained thrombolytic effects. Here an engineered probiotic driven micro‐rod robot for targeted and penetrative treatment for thrombus is developed. This micro‐robot can rapidly and accurately target and penetrate thrombus tissue; significantly prolonging the biological half‐life of thrombolytic drugs (≈332 times) and achieving sustained thrombolysis. This novel dual pronged thrombolytic therapy holds great scientific promise for the treatment of thrombotic diseases with shorter treatment time windows caused by vascular injury.

Superresolution imaging has revealed subcellular structures and protein interactions in many organisms. However, superresolution microscopy with lateral resolution better than 100 nm has not been achieved in photosynthetic cells due to the interference of a high-autofluorescence background. Here, we developed a photobleaching method to effectively reduce the autofluorescence of cyanobacterial and plant cells. We achieved lateral resolution of ~10 nm with stochastic optical reconstruction microscopy (STORM) in the sphere-shaped cyanobacterium Prochlorococcus and the flowering plant Arabidopsis thaliana . During the cell cycle of Prochlorococcus , we characterized the three-dimensional (3D) organization of the cell division protein FtsZ, which forms a ring structure at the division site and is important for cytokinesis of bacteria and chloroplasts. Although the FtsZ ring assembly process in rod-shaped bacteria has been studied extensively, it has rarely been studied in sphere-shaped bacteria. Similarly to rod-shaped bacteria, our results with Prochlorococcus also showed the assembly of FtsZ clusters into incomplete rings and then complete rings during cell division. Differently from rod-shaped bacteria, the FtsZ ring diameter was not found to decrease during Prochlorococcus cell division. We also discovered a novel double-Z-ring structure, which may be the Z rings of two daughter cells in a predivisional mother cell. Our results showed a quantitative picture of the in vivo Z ring organization of sphere-shaped bacteria. IMPORTANCE Superresolution microscopy has not been widely used to study photosynthetic cells due to their high-autofluorescence background. Here, we developed a photobleaching method to reduce the autofluorescence of cyanobacteria and plant cells. After photobleaching, we performed superresolution imaging in the cyanobacterium Prochlorococcus and the flowering plant Arabidopsis thaliana with ~10-nm resolution, which is the highest resolution in a photosynthetic cell. With this method, we characterized the 3D organization of the cell division protein FtsZ in Prochlorococcus . We found that the morphological variation of the FtsZ ring during cell division of the sphere-shaped cyanobacterium Prochlorococcus is similar but not identical to that of rod-shaped bacteria. Our method might also be applicable to other photosynthetic organisms. Superresolution microscopy has not been widely used to study photosynthetic cells due to their high-autofluorescence background. Here, we developed a photobleaching method to reduce the autofluorescence of cyanobacteria and plant cells. After photobleaching, we performed superresolution imaging in the cyanobacterium Prochlorococcus and the flowering plant Arabidopsis thaliana with ~10-nm resolution, which is the highest resolution in a photosynthetic cell. With this method, we characterized the 3D organization of the cell division protein FtsZ in Prochlorococcus . We found that the morphological variation of the FtsZ ring during cell division of the sphere-shaped cyanobacterium Prochlorococcus is similar but not identical to that of rod-shaped bacteria. Our method might also be applicable to other photosynthetic organisms.

The cyanobacterium Prochlorococcus is an essential member of global ocean ecosystems. Light rhythms drive Prochlorococcus photosynthesis, ecology, and interactions with potentially lethal viruses. At present, the impact of light on Prochlorococcus -virus interactions is not well understood. Here, we analyzed Prochlorococcus and virus population dynamics with a light-driven population model and compared our results with experimental data. Our approach revealed that light profoundly drives both cellular- and population-level dynamics for some host-virus systems. However, we also found that additional mechanisms, including lysis saturation, are required to explain observed host-virus dynamics at the population scale. This study provides the basis for future work to understand the intertwined fates of Prochlorococcus and associated viruses in the surface ocean. Prochlorococcus cyanobacteria grow in diurnal rhythms driven by diel cycles. Their ecology depends on light, nutrients, and top-down mortality processes, including lysis by viruses. Cyanophage, viruses that infect cyanobacteria, are also impacted by light. For example, the extracellular viability and intracellular infection kinetics of some cyanophage vary between light and dark conditions. Nonetheless, it remains unclear whether light-dependent viral life history traits scale up to influence population-level dynamics. Here, we examined the impact of diel forcing on both cellular- and population-scale dynamics in multiple Prochlorococcus -phage systems. To do so, we developed a light-driven population model, including both cellular growth and viral infection dynamics. We then tested the model against measurements of experimental infection dynamics with diel forcing to examine the extent to which population level changes in both viral and host abundances could be explained by light-dependent life history traits. Model-data integration reveals that light-dependent adsorption can improve fits to population dynamics for some virus-host pairs. However, light-dependent variation alone does not fully explain realized host and virus population dynamics. Instead, we show evidence consistent with lysis saturation at relatively high virus-to-cell ratios. Altogether, our study represents a quantitative approach to integrate mechanistic models to reconcile Prochlorococcus -virus dynamics spanning cellular-to-population scales. IMPORTANCE The cyanobacterium Prochlorococcus is an essential member of global ocean ecosystems. Light rhythms drive Prochlorococcus photosynthesis, ecology, and interactions with potentially lethal viruses. At present, the impact of light on Prochlorococcus -virus interactions is not well understood. Here, we analyzed Prochlorococcus and virus population dynamics with a light-driven population model and compared our results with experimental data. Our approach revealed that light profoundly drives both cellular- and population-level dynamics for some host-virus systems. However, we also found that additional mechanisms, including lysis saturation, are required to explain observed host-virus dynamics at the population scale. This study provides the basis for future work to understand the intertwined fates of Prochlorococcus and associated viruses in the surface ocean.

As an adaptation to the daily light–dark (diel) cycle, cyanobacteria exhibit diurnal rhythms of gene expression and cell cycle. The light–dark cycle also affects the life cycle of viruses (cyanophages) that infect the unicellular picocyanobacteria Prochlorococcus and Synechococcus, which are the major primary producers in the oceans. For example, the adsorption of some cyanophages to the host cells depends on light, and the burst sizes of cyanophages are positively correlated to the length of light exposure during infection. Recent metatranscriptomic studies revealed transcriptional rhythms of field cyanophage populations. However, the underlying mechanism remains to be determined, as cyanophage laboratory cultures have not been shown to exhibit diurnal transcriptional rhythms. Here, we studied variation in infection patterns and gene expression of Prochlorococcus phages in laboratory culture conditions as a function of light. We found three distinct diel-dependent life history traits in dark conditions (diel traits): no adsorption (cyanophage P-HM2), adsorption but no replication (cyanophage P-SSM2), and replication (cyanophage P-SSP7). Under light–dark cycles, each cyanophage exhibited rhythmic transcript abundance, and cyanophages P-HM2 and P-SSM2 also exhibited rhythmic adsorption patterns. Finally, we show evidence to link the diurnal transcriptional rhythm of cyanophages to the photosynthetic activity of the host, thus providing a mechanistic explanation for the field observations of cyanophage transcriptional rhythms. Our study identifies that cultured viruses can exhibit diurnal rhythms during infection, which might impact cyanophage population-level dynamics in the oceans.

Cyanopodoviruses affect the mortality and population dynamics of the unicellular picocyanobacteria Prochlorococcus and Synechococcus , the dominant primary producers in the oceans. Known cyanopodoviruses all contain the DNA polymerase gene (DNA pol ) that is important for phage DNA replication and widely used in field quantification and diversity studies. However, we isolated 18 cyanopodoviruses without identifiable DNA pol . They form a new MPP-C clade that was separated from the existing MPP-A, MPP-B, and P-RSP2 clades. The MPP-C phages have the smallest genomes (37.3–37.9 kb) among sequenced cyanophages, and show longer latent periods than the MPP-B phages. Metagenomic reads of both clades are highly abundant in surface waters, but the MPP-C phages show higher relative abundance in surface waters than in deeper waters, while MPP-B phages have higher relative abundance in deeper waters. Our study reveals that cyanophages with distinct genomic contents and infection kinetics can exhibit different depth profiles in the oceans.

Biochar is considered to have potential use in carbon (C) sequestration and has been widely used in soil amendment. Humic substances (HSs), assigned as the stable organic C, have obvious agronomic benefits. However, the response mechanisms of these carbonaceous substances to biochar are unclear in biochar-amended soils. In a two-year experiment, the δ13C technique was employed to trace the fate of the biochar-derived C in HSs and evaluate the effects of four treatments, including no biochar control (CK) and biochar addition at dosages of 6 t ha−1 (BC6), 12 t ha−1 (BC12), and 24 t ha−1 soil (BC24), on soil organic carbon (SOC) and HSs. Compared to CK, biochar application significantly improved total SOC contents and the C pool index, whereas the C labile index declined. Humic acid (HA) and humin were distinctly enhanced in bulk soil. Moreover, the aliphaticity was intensified in the chemical composition of HA. In particular, native HA contents substantially increased by 16.30–55.95%. Biochar-applied C of 4.08–6.43% was finitely involved in HA formation over the two years, which resulted in a genetic relationship between soil HA and biochar to some extent. The low dosages of biochar at 6 t ha−1, 12 t ha−1 and 24 t ha−1 did not obviously affect native SOC contents. Moreover, BC24 had less of an effect on HA formation compared to BC6 and BC12, but had the highest SOC. These results demonstrate that biochar application can improve SOC stocks, reduce C instability and promote HSs formation, and they suggest that determining and keeping an optimum dosage of biochar application can represent an effective strategy (i.e., not only sequestrate C, but also improve soil quality), which is beneficial to sustainability in the ecological environment and agriculture.

The marine cyanobacterium Prochlorococcus is one of the most abundant unicellular photosynthetic organisms in the oceans, being a major contributor to carbon fixation in aquatic environments. Cyanophages are viruses that infect cyanobacteria and release cellular components into the marine ecosystem, contributing greatly to global biogeochemical cycles. As an adaptation to the daily light-dark (diel) cycle, cyanobacteria exhibit diurnal rhythms of gene expression and cell cycle. The light-dark cycle also affects the life cycle of cyanophages. Recent metatranscriptomic studies revealed transcriptional rhythms of field cyanophage populations. However, the underlying mechanism remains to be determined, as cyanophage laboratory cultures have not been shown to exhibit diurnal transcriptional rhythms. Here, before studying cyanophage infection under light-dark cycles, I first characterized synchronized Prochlorococcus, and showed a three-dimensional (3D) organization dynamics of the cell division protein FtsZ during the cell cycle. Then, I studied variation in infection patterns and gene expression of Prochlorococcus phages in laboratory culture conditions as a function of light. I found three distinct diel-dependent life history traits in dark conditions (diel traits): no adsorption (cyanophage P-HM2), adsorption but no replication (cyanophage P-SSM2), and replication (cyanophage P-SSP7). Under light-dark cycles, each cyanophage exhibited rhythmic transcript abundance, and the cyanophages P-HM2 and P-SSM2 also exhibited rhythmic adsorption patterns. I further showed evidence to link the diurnal transcriptional rhythm of cyanophages to the photosynthetic activity of the host, thus providing a mechanistic explanation for the field observations of cyanophage transcriptional rhythms. Finally, I compared the relative fitness of cyanophages that showed different life history traits; I allowed laboratory-cultured cyanophages that showed different life history traits to compete and measured the relative abundance of cyanophages with different life history traits that were isolated from the South China Sea. I found that with limited bench culture, P-HM2 had a fitness advantage over P-SSP7 under light-dark cycles and that P-SSM2 outcompeted P-HM2 under continuous light and under light-dark cycles. However, among the field-isolated cyanophages, P-SSP7–like cyanophages had the highest relative fitness. The results suggested a potential coexistence mechanism for the three life history traits. My study identifies that cultured viruses can exhibit diurnal rhythms during infection, which might impact cyanophage population-level dynamics in the oceans.

Prochlorococcus grow in diurnal rhythms driven by diel cycles. Their ecology depends on light, nutrients, and top-down mortality processes including lysis by viruses. Cyanophage, viruses that infect cyanobacteria, are also impacted by light. For example, extracellular viability and intracell infection kinetics of some cyanophage vary between light and dark conditions. Nonetheless, it remains unclear if light-dependent viral life history traits scale-up to influence population-level dynamics. Here we examined the impact of diel-forcing on both cellular- and population-scale dynamics in multiple Prochlorococcus-phage systems. To do so, we developed a light-driven population model including both cellular growth and viral infection dynamics. We then tested the model against measurements of experimental infection dynamics with diel forcing to examine the extent to which population level changes in both viral and host abundances could be explained by light-dependent life history traits. Model-data integration reveals that light-dependent adsorption can improve fits to population dynamics for some virus-host pairs. However, light-dependent variation alone does not fully explain realized host and virus population dynamics. Instead, we show evidence of a previously unrecognized lysis saturation at relatively high virus to cell ratios. Altogether, our study represents a quantitative approach to integrate mechanistic models to reconcile Prochlorococcus-virus dynamics spanning cellular to population scales.