Development of a base editor for convenient and multiplex genome editing in cyanobacteria.

Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.

Quaternary Dielectric Triboelectric Nanogenerator for Self-Powered Electrochemical Systems.

The energy conversion efficiency of conventional binary dielectric triboelectric nanogenerators is not satisfactory due to the limitations of material selection and triboelectrification, which motivates the design of more efficient multicomponent structures to reveal the charge accumulation mechanism for improving the energy conversion efficiency. Herein, a rotating quaternary dielectric triboelectric nanogenerator (Q-TENG) is designed to construct a self-powered system integrating illumination, sensing, and electrochemical decolorization. Through the equivalent capacitance model, the mechanisms for charge generation, transfer, and accumulation in a Q-TENG are elucidated to achieve efficient matching of quaternary dielectric materials and high output performance. At a wind speed of 3.5 m s-1, the peak power density of the Q-TENG reaches 44.94 W m-2, setting a new record for a wind-driven TENG. A 5 ppm solution of methyl orange is completely degraded by the wind-driven Q-TENG in <6 h. This work not only guides the direction for constructing more efficient TENG systems but also promotes the practical development of self-powered electrochemical systems.

Achieving Ultrahigh DC-Power Triboelectric Nanogenerators by Lightning Rod-Inspired Field Emission Modeling.

Direct current triboelectric nanogenerators (DC-TENGs) are a groundbreaking technology to capture micromechanical energy from the natural environment, which is crucial for directly powering sensor networks. However, the research bottleneck in enhancing the triboelectric electrification capability and charge storage capability of dielectrics has hindered the overall performance breakthroughs of the DC-TENG. Here, a field emission model-based DC-TENG (FEM-TENG) is proposed, inspired by lightning rods. The enhanced local electric field between dielectric materials and electrodes induces strong electron tunneling, which improves charge neutralization on the surface of materials and their internal charge storage space, thereby utilizing the dielectric volume effect effectively and strengthening triboelectricity. Guided by the field emission model, the FEM-TENG with a historic crest factor of 1.00375 achieves a groundbreaking record of an average power density of 16.061 W m-2 Hz-1 (1,591 W m-3 Hz-1), which is 5.36-fold of the latest DC-TENG. In particular, the FEM-TENG with high durability (100%) truly realizes the collection of breeze energy and continuously drives 50 thermohygrometers. Four additional applications exemplify the FEM-TENG, enabling comprehensive sensing of land, water, and air. This work proposes a paradigm strategy for the in-depth utilization of dielectric films, aiming to enhance the output power of DC-TENGs.

A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

Desensitization Strategies for Donor-Specific Antibodies in HLA-Mismatched Stem Cell Transplantation Recipients: What We Know and What We Do Not Know.

In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application.

Differential drought tolerance among dichondra (Dichondra repens) genotypes in relation to alterations in chlorophyll metabolism, osmotic adjustment, and accumulation of organic metabolites.

Dichondra (Dichondra repens) is an important ground cover plant for landscaping and establishment of green space, but adaptive mechanism of drought tolerance is not well understood in this species. This study was conducted to compare differential response to drought stress among three genotypes (Dr5, Duliujiang, and Dr29) based on integrated physiological, ultrastructural, and metabolic assays. Results showed that drought significantly inhibited photosynthesis, accelerated lipids peroxidation, and also disrupted water balance and cellular metabolism in dichondra plants. Dr5 showed better photochemical efficiency of photosystem II and water homeostasis, less oxidative damage, and more stable chlorophyll metabolism than Duliujinag or Dr29 in response to drought stress. In addition, Dr5 accumulated more amino acids, organic acids, and other metabolites, which was good for maintaining better antioxidant capacity, osmotic homeostasis, and energy metabolism under drought stress. Drought tolerance of Duliujiang was lower than Dr5, but better than Dr29, which could be positively correlated with accumulations of sucrose, maltitol, aconitic acid, isocitric acid, and shikimic acid due to critical roles of these metabolites in osmotic adjustment and metabolic homeostasis. Current findings provide insights into understanding of underlying mechanism of metabolic regulation in dichondra species. Dr5 could be used as an important drought-tolerant resource for cultivation and water-saving breeding.

Temporal Distribution Patterns of Cryptic Brachionus calyciflorus (Rotifera) Species in Relation to Biogeographical Gradient Associated with Latitude.

Sympatric distribution and temporal overlap of cryptic zooplankton species pose a challenge to the framework of the niche differentiation theory and the mechanisms allowing competitor coexistence. We applied the methods of phylogenetic analysis, DNA taxonomy, and statistical analysis to study the temporal distribution patterns of the cryptic B. calyciflorus species, an excellent model, in three lakes, and to explore the putative mechanisms for their seasonal succession and temporal overlap. The results showed that in the warm-temperate Lake Yunlong, B. fernandoi and B. calyciflorus s.s. underwent a seasonal succession, which was largely attributed to their differential adaptation to water temperature. In the subtropical Lake Jinghu, B. fernandoi, B. calyciflorus s.s., and B. dorcas exhibited both seasonal succession and temporal overlap. Seasonal successions were largely attributed to their differential adaptation to temperature, and temporal overlap resulted from their differential responses to algal food concentration. In the tropical Lake Jinniu, B. calyciflorus s.s. persisted throughout the year and overlapped with B. dorcas for 5 months. The temporal overlap resulted from their differential responses to copepod predation. These results indicated that the temporal distribution pattern of the cryptic B. calyciforus species and the mechanism that allows competitor coexistence vary with different climate zones.

[Correlation between drug-induced liver injury in rats caused by Xianling Gubao oral preparation and extraction process].

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.