Systemic immune responses do not affect significant immune responses in the skin.

Fish skin plays an important role in defending against pathogens in water, primarily through the secretion of skin mucus containing various immune-related factors. Local immune responses in the skin activate systemic immune responses by inflammatory cytokines. However, it remains unclear whether immune responses in the skin occur after systemic immune responses caused by pathogen invasion into the fish body. This study aimed to clarify the relationship between systemic immune responses and skin responses after intraperitoneal injection of formalin-killed cells (FKC) of Vibrio anguillarum. Although systemic inflammatory responses were observed in the spleen after injection, expression changes in the skin did not show significant differences. In contrast, expression of hemoglobin subunit genes significantly increased in the skin after FKC injection, suggesting that erythrocytes infiltrate extravascularly.

Investigating the molecular mechanisms of Pseudalteromonas sp. LD-B1's algicidal effects on the harmful alga Heterosigma akashiwo.

Heterosigma akashiwo is a harmful algal bloom species that causes significant detrimental effects on marine ecosystems worldwide. The algicidal bacterium Pseudalteromonas sp. LD-B1 has demonstrated potential effectiveness in mitigating these blooms. However, the molecular mechanisms underlying LD-B1's inhibitory effects on H. akashiwo remain poorly understood. In this study, we employed the comprehensive methodology, including morphological observation, assessment of photosynthetic efficiency (Fv/Fm), and transcriptomic analysis, to investigate the response of H. akashiwo to LD-B1. Exposure to LD-B1 resulted in a rapid decline of H. akashiwo's Fv/Fm ratio, with cells transitioning to a rounded shape within 2 hours, subsequently undergoing structural collapse and cytoplasmic leakage. Transcriptomic data revealed sustained downregulation of photosynthetic genes, indicating impaired functionality of the photosynthetic system. Additionally, genes related to the respiratory electron transfer chain and antioxidant defenses were consistently downregulated, suggesting prolonged oxidative stress beyond the cellular antioxidative capacity. Notably, upregulation of autophagy-related genes was observed, indicating autophagic responses in the algal cells. This study elucidates the molecular basis of LD-B1's algicidal effects on H. akashiwo, advancing our understanding of algicidal mechanisms and contributing to the development of effective strategies for controlling harmful algal blooms.

Enhanced Genomic and Transcriptomic Resources for Trichinella pseudospiralis and T. spiralis to Underpin the Discovery of Molecular Differences between Stages and Species.

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host-parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin-with possible roles in modulating host immune responses and facilitating parasite survival-were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella-host interactions might offer possible avenues for developing new interventions against trichinellosis.

Integrated transcriptomic and metabolomic analysis reveals the underlying mechanisms for male reproductive toxicity of polystyrene nanoplastics in mouse spermatocyte-derived GC-2spd(ts) cells.

BACKGROUND: Polystyrene nanoplastics (PS-NPs), are ubiquitous pollution sources in human environments, posing significant biosafety and health risks. While recent studies, including our own, have illustrated that PS-NPs can breach the blood-testis barrier and impact germ cells, there remains a gap in understanding their effects on specific spermatogenic cells such as spermatocytes. METHODS AND RESULTS: Herein, we employed an integrated approach encompassing phenotype, metabolomics, and transcriptomics analyses to assess the molecular impact of PS-NPs on mouse spermatocyte-derived GC-2spd(ts) cells. Optimal exposure conditions were determined as 24 h with 50 nm PS-NPs at 12.5 µg/mL and 90 nm PS-NPs at 50 µg/mL for subsequent multi-omics analysis. Our findings revealed that PS-NPs significantly influenced proliferation and viability, causing alterations in transcriptome and metabolome profiles. Transcriptomics analysis of GC-2spd(ts) cells exposed to PS-NPs indicated the pivotal involvement of cell proliferation and cycle, autophagy, ferroptosis, and redox reaction pathways in PS-NP-induced effects on the proliferation and viability of GC-2spd(ts) cells. Furthermore, metabolomics analysis identified major changes in amino acid metabolism, cyanoamino acid metabolism, and purine and pyrimidine metabolism following PS-NP exposure. CONCLUSION: Our integrated approach, combining metabolomics and transcriptomics profiles with phenotype data, enhances our understanding of the adverse effects of PS-NPs on germ cells.

The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

ELFN1 is a new extracellular matrix (ECM)-associated protein.

AIMS: The ELFN1, discovered in 2007, is a single-pass transmembrane protein. Studies conducted thus far to elucidate the function of the Elfn1 have been limited only to animal studies. These studies have reported that ELFN1 is a universal binding partner of metabotropic glutamate receptors (mGluRs) in the central nervous system and its functional deficiency has been associated with the pathogenesis of neurological and neuropsychiatric diseases. In 2021, we described the first disease-associated human ELFN1 pathogenic gene mutation. Severe joint laxity, which was the most striking finding of this new disease and was clearly seen in the patients since early infancy, showed that the ELFN1 may have a possible function in the connective tissue besides the nervous system. Here, we present the first experimental evidence of the extracellular matrix (ECM)-related function of the ELFN1. MATERIALS AND METHODS: Primary skin fibroblasts were isolated from the skin biopsies of ELFN1 mutated patients and healthy foreskin donors. For the clinical trial in a dish, in vitro ECM and DEM (decellularized ECM) models were created from skin fibroblasts. All the in vitro models were comparatively characterized and analyzed. KEY FINDINGS: The mutation in the ELFN1 signal peptide region of patients resulted in a severe lack of ELFN1 expression and dramatically altered the characteristic morphology and behavior (growth, proliferation, and motility) of fibroblasts. SIGNIFICANCE: We propose that ELFN1 is involved in the cell-ECM attachment, and its deficiency is critical enough to cause a loss of cell motility and soft ECM stiffness.

A dual RNA-seq analyses revealed dynamic arms race during the invasion of walnut by Colletotrichum gloeosporioides.

BACKGROUND: Walnut anthracnose caused by Colletotrichum gloeosporioides seriously endangers the yield and quality of walnut, and has now become a catastrophic disease in the walnut industry. Therefore, understanding both pathogen invasion mechanisms and host response processes is crucial to defense against C. gloeosporioides infection. RESULTS: Here, we investigated the mechanisms of interaction between walnut fruits (anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts) and C. gloeosporioides at three infection time points (24hpi, 48hpi, and 72hpi) using a high-resolution time series dual transcriptomic analysis, characterizing the arms race between walnut and C. gloeosporioides. A total of 20,780 and 6670 differentially expressed genes (DEGs) were identified in walnut and C. gloeosporioides against 24hpi, respectively. Generous DEGs in walnut exhibited opposite expression patterns between F26 and F423, which indicated that different resistant materials exhibited different transcriptional responses to C. gloeosporioides during the infection process. KEGG functional enrichment analysis indicated that F26 displayed a broader response to C. gloeosporioides than F423. Meanwhile, the functional analysis of the C. gloeosporioides transcriptome was conducted and found that PHI, SignalP, CAZy, TCDB genes, the Fungal Zn (2)-Cys (6) binuclear cluster domain (PF00172.19) and the Cytochrome P450 (PF00067.23) were largely prominent in F26 fruit. These results suggested that C. gloeosporioides secreted some type of effector proteins in walnut fruit and appeared a different behavior based on the developmental stage of the walnut. CONCLUSIONS: Our present results shed light on the arms race process by which C. gloeosporioides attacked host and walnut against pathogen infection, laying the foundation for the green prevention of walnut anthracnose.

Physical cell-cell contact elicits specific transcriptomic responses in wine yeast species.

Fermenting grape juice provides a habitat for a well-mapped and evolutionarily relevant microbial ecosystem consisting of many natural or inoculated strains of yeasts and bacteria. The molecular nature of many of the ecological interactions within this ecosystem remains poorly understood, with the partial exception of interactions of a metabolic nature such as competition for nutrients and production of toxic metabolites/peptides. Data suggest that physical contact between species plays a significant role in the phenotypic outcome of interspecies interactions. However, the molecular nature of the mechanisms regulating these phenotypes remains unknown. Here, we present a transcriptomic analysis of physical versus metabolic contact between two wine relevant yeast species, Saccharomyces cerevisiae and Lachancea thermotolerans. The data show that these species respond to the physical presence of the other species. In S. cerevisiae, physical contact results in the upregulation of genes involved in maintaining cell wall integrity, cell wall structural components, and genes involved in the production of H2S. In L. thermotolerans, HSP stress response genes were the most significantly upregulated gene family. Both yeasts downregulated genes belonging to the FLO family, some of which play prominent roles in cellular adhesion. qPCR analysis indicates that the expression of some of these genes is regulated in a species-specific manner, suggesting that yeasts adjust gene expression to specific biotic challenges or interspecies interactions. These findings provide fundamental insights into yeast interactions and evolutionary adaptations of these species to the wine ecosystem.IMPORTANCEWithin the wine ecosystem, yeasts are the most relevant contributors to alcoholic fermentation and wine organoleptic characteristics. While some studies have described yeast-yeast interactions during alcoholic fermentation, such interactions remain ill-defined, and little is understood regarding the molecular mechanisms behind many of the phenotypes observed when two or more species are co-cultured. In particular, no study has investigated transcriptional regulation in response to physical interspecies cell-cell contact, as opposed to the generally better understood/characterized metabolic interactions. These data are of direct relevance to our understanding of microbial ecological interactions in general while also creating opportunities to improve ecosystem-based biotechnological applications such as wine fermentation. Furthermore, the presence of competitor species has rarely been considered an evolutionary biotic selection pressure. In this context, the data reveal novel gene functions. This, and further such analysis, is likely to significantly enlarge the genome annotation space.

PHLDA1-PRDM1 mediates the effect of lentiviral vectors on fate-determination of human retinal progenitor cells.

Lentiviral vectors have markedly enhanced gene therapy efficiency in treating congenital diseases, but their long-term safety remains controversial. Most gene therapies for congenital eye diseases need to be carried out at early ages, yet the assessment of related risks to ocular development posed by lentiviral vectors is challenging. Utilizing single-cell transcriptomic profiling on human retinal organoids, this study explored the impact of lentiviral vectors on the retinal development and found that lentiviral vectors can cause retinal precursor cells to shift toward photoreceptor fate through the up-regulation of key fate-determining genes such as PRDM1. Further investigation demonstrated that the intron and intergenic region of PRDM1 was bound by PHLDA1, which was also up-regulated by lentiviral vectors exposure. Importantly, knockdown of PHLDA1 successfully suppressed the lentivirus-induced differentiation bias of photoreceptor cells. The findings also suggest that while lentiviral vectors may disrupt the fate determination of retinal precursor cells, posing risks in early-stage retinal gene therapy, these risks could potentially be reduced by inhibiting the PHLDA1-PRDM1 axis.

Hepatic transcriptomic assessment of Sprague Dawley rats in response to dietary perfluorobutane sulfonate (PFBS) ingestion.

Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats.

Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients.

BACKGROUND: The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. METHODS: We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. RESULTS: We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. CONCLUSION: Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets.

Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance.

The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Chitosan-modified molybdenum selenide mediated efficient killing of Helicobacter pylori and treatment of gastric cancer.

Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.

Transcriptomic analysis reveals zinc-mediated virulence and pathogenicity in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a gram-negative bacterium well known for its multidrug resistance and connection to nosocomial infections under ESKAPE pathogens. This opportunistic pathogen is ubiquitously associated with nosocomial infections, posing significant threats within healthcare environments. Its critical clinical symptoms, namely, meningitis, urinary tract infections, bloodstream infections, ventilator-associated pneumonia, and pneumonia, catalyze the imperative demand for innovative therapeutic interventions. The proposed research focuses on delineating the role of Zinc, a crucial metallo-binding protein and micronutrient integral to bacterial metabolism and virulence, to enhance understanding of the pathogenicity of A. baumannii. RNA sequencing and subsequent DESeq2 analytical methods were used to identify differential gene expressions influenced by zinc exposure. Exploiting the STRING database for functional enrichment analysis has demonstrated the complex molecular mechanisms underlying the enhancement of pathogenicity prompted by Zinc. Moreover, hub genes like gltB, ribD, AIL77834.1, sdhB, nuoI, acsA_1, acoC, accA, accD were predicted using the cytohubba tool in Cytoscape. This investigation underscores the pivotal role of Zinc in the virulence of A. baumannii elucidates the underlying molecular pathways responsible for its pathogenicity. The research further accentuates the need for innovative therapeutic strategies to combat A. baumannii infections, particularly those induced by multidrug-resistant strains.

Transcriptomic Differences in Medullary Thyroid Carcinoma According to Grade.

Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC.

Integrative metabolomics and transcriptomics analysis revealed specific genes and metabolites affecting meat quality of chickens under different rearing systems.

Different rearing systems have varying effect on animal welfare and meat quality of poultry. Currently, there are no established standards for the rearing systems of Chinese indigenous chickens. Our study aimed to investigate the effects of different rearing systems on the meat quality, gene profiles, and metabolites of Chinese indigenous chickens (Nanchuan chicken). 10-wk-old Nanchuan chickens (n=360) were randomly divided into 3 groups (cage, net, and free-range groups), with 6 replicates per group (20 chickens per replicate). The experiment lasted for 12 wk. At 154-days-old, 36 healthy chickens (6 males and 6 females per group) were randomly selected, euthanized, and their breast muscles were collected to assess the meat quality parameters and histomorphological characteristics. Additionally, breast muscles from 18 random hens (3 males and 3 females per group) were used for metabolomics and RNA-seq analysis. The results showed that rearing systems significantly affected the meat quality and myofiber characteristics. The meat quality of breast muscles from free-range chickens was superior to that of caged chickens, characterized by more tender meat and smaller myofiber cross-sectional areas. Integrative metabolomics and transcriptomics analysis revealed that the differentially expressed genes of chicken breast muscles were primarily involved in the myofiber differentiation. Mechanically, the improved meat quality of breast muscle in free-range chickens were mainly associated with enhanced skeletal muscle differentiation facilitated by fibromodulin, increased levels of up-regulated Acetyl-L-carnitine and Propionylcarnitine level, and decreased levels of Nonanoic acid and Elaidic acid abundance (Graphical abstract). This provides a comprehensive understanding of the most effective and sustainable breeding, production, and rearing systems for Chinese indigenous chickens. It also contributes to the current knowledge of the molecular mechanisms underlying the effects of rearing systems on growth performance and meat quality of chickens.

Molecular mechanisms underlying sodium percarbonate treatment suppress the recovery and growth of Pseudanabaena sp. in early spring.

Increasing frequency and intensity of cyanobacterial blooms in water sources is a growing global issue. Algicides are usually implemented in summer or autumn when blooms break out, however, the blooms will form again when algicide's concentration declines to a certain extent. Preventing the recovery and growth of cyanobacteria in early spring may be conducive to abatement of the blooms in summer or autumn. In this study solid sodium percarbonate (SPC) was used as an algicide to suppress recovery and growth of Pseudanabaena sp., a common odour-producing cyanobacterium, in early spring (12 °C). Results showed that 3.0 and 6.0 mg/L SPC were able to kill most of the algal cells after 12 h treatment at 12 °C, and the residual cells gradually died during the re-cultivation period at 25 °C. As a control, although SPC also caused most of algal cells to lyse at 25 °C, regrowth of cells was found during the period of re-cultivation at 25 °C. Transcriptomic analysis revealed that the dysregulated genes were strongly associated with translation and photosynthesis after SPC treatment. All differentially expressed unigenes related to translation and photosynthesis were down-regulated after SPC oxidation at 12 °C, whereas key genes associated with translation and photosynthesis were upregulated after SPC treatment at 25 °C.

Astragalus mongholicus Bunge extract improves ulcerative colitis by promoting PLCB2 to inhibit colonic epithelial cell pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AM) and its active ingredients are mainly used for anti-inflammatory, antiviral, antioxidant, immune regulation, cardiovascular and nervous system protection, anti-cancer, anti-tumor and so on. AIM OF THE STUDY: To explore the Astragalus mongholicus Bunge extract pharmacological mechanisms and biology processes which improves ulcerative colitis (UC). MATERIALS AND METHODS: Dextran sulfate sodium (DSS)-induced UC models in C57BL/6 mice were established, and the mice were treated with Astragalus mongholicus Bunge extract or salazosulfapyridine (SASP). DSS-induced mice- and human-derived colonic epithelial cell lines were used to reveal the inflammatory environment of UC. After treatment with Astragalus mongholicus Bunge extract, the expression of phospholipase C-ß 2 (PLCB2) in the cells was detected by quantitative real-time PCR (qRT-PCR), and cell proliferative activity was detected by cell counting kit 8 (CCK-8) assay. Finally, the levels of pyroptosis-related inflammatory factors in cell culture supernatants was detected by ELISA. RESULTS: Treatment of UC mice with Astragalus mongholicus Bunge extract do significantly improved DAI scores and histopathological damage scores, and decreased the levels of Eotaxin, GCSF, KC, MCP-1, TNF-α, and IL-6. Besides, Astragalus mongholicus Bunge extract inhibited the expression of nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3), cleaved Caspase-1, and GSDMD-N in the colonic tissues, and reduced the levels of inflammation-related factors IL-1ß and IL-18 in serum and tissues. In vitro, Astragalus mongholicus Bunge extract partially reversed the DSS-induced reduction of PLCB2 expression in CP-M030 and NCM460, promoted cell proliferative activity, and reduced the levels of IL-1ß and IL-18. CONCLUSIONS: In DDS-induced UC mice, Astragalus mongholicus Bunge extract improves ulcerative colitis by inhibiting colonic epithelial cell pyroptosis through PLCB2 promotion.