Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic ß cell Pyroptosis upon Viral Infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and ß cell pyroptosis. To distinguish viral versus proinflammatory macrophage-mediated ß cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both ß cells and endothelial cells compared to separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced ß cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory macrophage-mediated ß cell pyroptosis. This study established hPSC- derived VMI organoids as a valuable tool for studying immune cell-mediated host damage and uncovered mechanism of ß cell damage during viral exposure.

Effects of low-molecular-weight organic acids on the transformation and phosphate retention of iron (hydr)oxides.

The retention and mobilization of phosphate in soils are closely associated with the adsorption of iron (hydr)oxides and root exudation of low-molecular-weight organic acids (LMWOAs). This study investigated the role of LMWOAs in phosphate mobilization under incubation and field conditions. LMWOAs-mediated iron (hydr)oxide transformation and phosphate adsorption experiments revealed that the presence of LMWOAs decreased the phosphate adsorption capacity of iron (hydr)oxides by up to ~74 % due to the competition effect, while LMWOAs-induced iron mineral transformation resulted in an approximately six-fold increase in phosphate retention by decreasing the crystallinity and increasing the surface reactivity. Root simulation in rhizobox experiments demonstrated that LMWOAs can alter the contents of different extractable phosphate species and iron components, leading to 10 % ~ 30 % decreases in available phosphate in the near root region of two tested soils. Field experiments showed that crop covering between mango tree rows promoted the exudation of LMWOAs from mango roots. In addition, crop covering increased the contents of total phosphate and available phosphate by 9.08 % ~ 61.20 % and 34.33 % ~ 147.33 % in the rhizosphere soils of mango trees, respectively. These findings bridge the microscale and field scale to understand the delicate LMWOAs-mediated balance between the retention and mobilization of phosphate on iron (hydr)oxide surface, thereby providing important implications for mitigating the low utilization efficiency of phosphate in iron-rich soils.

Glycosyltransferase Slr1064 regulates carbon metabolism by modulating the levels of UDP-GlcNAc in Synechocystis sp. PCC 6803.

Glycosyltransferases (GTs) are enzymes that transfer sugars to various targets. They play important roles in diverse biological processes, including photosynthesis, cell motility, exopolysaccharide biosynthesis, and lipid metabolism; however, their involvement in regulating carbon metabolism in Synechocystis sp. PCC 6803 has not been reported. We identified a novel GT protein, Slr1064, involved in carbon metabolism. The effect of slr1064 deletion on the growth of Synechocystis cells and functional mechanisms of Slr1064 on carbon metabolism were thoroughly investigated through physiological, biochemistry, proteomic, and metabolic analyses. We found that this GT, which is mainly distributed in the membrane compartment, is essential for the growth of Synechocystis under heterotrophic and mixotrophic conditions, but not under autotrophic conditions. The deletion of slr1064 hampers the turnover rate of Gap2 under mixotrophic conditions and disrupts the assembly of the PRK/GAPDH/CP12 complex under dark culture conditions. Additionally, UDP-GlcNAc, the pivotal metabolite responsible for the O-GlcNAc modification of GAPDH, is downregulated in the Δslr1064. Our work provides new insights into the role of GTs in carbon metabolism in Synechocystis and elucidate the mechanism by which carbon metabolism is regulated in this important model organism.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Chromosome-level genome assembly of Pedicularis kansuensis illuminates genome evolution of facultative parasitic plant.

Parasitic plants have a heterotrophic lifestyle, in which they withdraw all or part of their nutrients from their host through the haustorium. Despite the release of many draft genomes of parasitic plants, the genome evolution related to the parasitism feature of facultative parasites remains largely unknown. In this study, we present a high-quality chromosomal-level genome assembly for the facultative parasite Pedicularis kansuensis (Orobanchaceae), which invades both legume and grass host species in degraded grasslands on the Qinghai-Tibet Plateau. This species has the largest genome size compared with other parasitic species, and expansions of long terminal repeat retrotransposons accounting for 62.37% of the assembly greatly contributed to the genome size expansion of this species. A total of 42,782 genes were annotated, and the patterns of gene loss in P. kansuensis differed from other parasitic species. We also found many mobile mRNAs between P. kansuensis and one of its host species, but these mobile mRNAs could not compensate for the functional losses of missing genes in P. kansuensis. In addition, we identified nine horizontal gene transfer (HGT) events from rosids and monocots, as well as one single-gene duplication events from HGT genes, which differ distinctly from that of other parasitic species. Furthermore, we found evidence for HGT through transferring genomic fragments from phylogenetically remote host species. Taken together, these findings provide genomic insights into the evolution of facultative parasites and broaden our understanding of the diversified genome evolution in parasitic plants and the molecular mechanisms of plant parasitism.

SARS-CoV-2 infection causes dopaminergic neuron senescence.

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

MODMS: a multi-omics database for facilitating biological studies on alfalfa (Medicago sativa L.).

Alfalfa (Medicago sativa L.) is a globally important forage crop. It also serves as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Multi-omics data on alfalfa continue to accumulate owing to recent advances in high-throughput techniques, and integrating this information holds great potential for expediting genetic research and facilitating advances in alfalfa agronomic traits. Therefore, we developed a comprehensive database named MODMS (multi-omics database of M. sativa) that incorporates multiple reference genomes, annotations, comparative genomics, transcriptomes, high-quality genomic variants, proteomics, and metabolomics. This report describes our continuously evolving database, which provides researchers with several convenient tools and extensive omics data resources, facilitating the expansion of alfalfa research. Further details regarding the MODMS database are available at https://modms.lzu.edu.cn/.