CRISPR dynamics during the interaction between bacteria and phage in the first year of life

Gut microbiomes in infancy have a profound impact on health in adulthood. CRISPRs play an essential role in the interaction between bacteria and phages. However, the dynamics of CRISPRs in gut microbiomes during early life are poorly understood. In this study, using shotgun metagenomic sequencing data from 82 Swedish infants' gut microbiomes, 1882 candidate CRISPRs were identified, and their dynamics were analysed. We found large-scale turnover of CRISPRs and their spacers during the first year of life. As well as changes in relative abundance of the bacteria containing CRISPR, acquisition, loss and mutation of spacers were observed within the same CRISPR array sampled over time. Accordingly, the inferred interaction network of bacteria and phage was distinct at different times. This research underpins CRISPR dynamics and their potential role in the interaction between bacteria and phage in early life.</p

Synthesis of conjugated linoleic acid-rich triacylglycerols by immobilized mutant lipase with excellent capability and recyclability

Conjugated linoleic acid (CLA)-rich triacylglycerols (TAG) have received significant attention owing to their health promoting properties. In this study, CLA-rich TAG were successfully synthesized by an immobilized mutant lipase (MAS1-H108A)-catalyzed esterification of CLA-rich fatty acids and glycerol under vacuum. MAS1-H108A was first immobilized onto ECR1030 resin. Results showed that the lipase/support ratio of 41 mg/g was suitable for the immobilization and the thermostability of immobilized MAS1-H108A was greatly enhanced. Subsequently, the immobilized MAS1-H108A was employed for the synthesis of CLA-rich TAG and 95.21% TAG with 69.19% CLA was obtained under the optimized conditions. The TAG content (95.21%) obtained by immobilized MAS1-H108A is the reported highest value thus far, which was significantly higher than that (9.26%) obtained by Novozym 435 under the same conditions. Although the TAG content comparable to the results obtained in this study could also be obtained by Novozym 435, the used enzyme amount is approximately 5-fold of the immobilized MAS1-H108A. Additionally, the immobilized MAS1-H108A exhibited excellent recyclability during esterification retaining 95.11% of its initial activity after 10 batches. Overall, such immobilized mutant lipase with superior esterification activity and recyclability has the potential to be used in oils and fats industry

A snapshot of the transition from monogenetic volcanoes to composite volcanoes: Case study on the Wulanhada Volcanic Field (northern China)

The transition processes from monogenetic volcanoes to composite volcanoes are poorly understood. The Late Pleistocene to Holocene intraplate monogenetic Wulanhada Volcanic Field (WVF) in northern China provides a snapshot of such a transition. Here we present petrographic observations, mineral chemistry, bulk rock major and trace element data, thermobarometry, and a partial melting model for the WVF to evaluate the lithology and partial melting degree of the mantle source, the crystallization conditions, and pre-eruptive magmatic processes occurring within the magma plumbing system. The far-field effect of India-Eurasia collision resulted in a relatively high degree (10 %-20 %) of partial melting of a carbonate-bearing eclogite (~ 3 wt % carbonate; Gt/Cpx ≈ 2 : 8, where Gt denotes garnet and Cpx denotes clinopyroxene) followed by interaction with ambient peridotite. The primary melts ascended to the depth of the Moho (~ 33-36 km depth), crystallized olivine, clinopyroxene and plagioclase at the temperature of 1100-1160 °C with the melt water contents of 1.1 wt %- 2.3 wt %. Part of the primary melt interacted with the lithospheric mantle during ascent, resulting in an increase in the MgO contents and a decrease in the alkaline contents. The modified magma was subsequently directly emplaced into the middle crust (~ 23-26 km depth) and crystallized olivine, clinopyroxene and plagioclase at the temperature of 1100-1160 °C. The primary melts from the same mantle sources migrated upward to the twolevel magma reservoirs to form minerals with complex textures (including reverse and oscillatory zoning and sieve texture). Magma erupted along the NE-SW-striking basement fault and the NW-SE-striking Wulanhada- Gaowusu fault in response to the combined effects of regional tectonic stress and magma replenishment. The crustal magma reservoir in the WVF may represent a snapshot of the transition from monogenetic volcanoes to composite volcanoes. It is possible to form a composite volcano with large magma volumes and complex compositions if the magma is continuously supplied from the source and experiences assimilation and fractional crystallization processes in the magma plumbing system at crustal depth

Deep eutectic solvents enable the enhanced production of n-3 PUFA-enriched triacylglycerols

Efficient synthesis of n‐3 PUFA‐enriched triacylglycerol (TAG) by the esterification of glycerol with n‐3 PUFA in deep eutectic solvents (DES) is reported. There was a 1.2‐fold increase of TAG yield in DES compared with that in the solvent‐free system. Adsorption of the produced water by DES during esterification contributed to enhance the conversion efficiency by changing the reaction equilibrium. DES also served as an effective solvent for enriching the n‐3 PUFA of TAG in the upper layer of reaction media. A TAG yield of 55% was achieved under the optimal condition. Practical Applications: Enzymatic synthesis of n‐3 PUFA‐enriched triacylglycerol (TAG) is challenged by low yields. Here, deep eutectic solvents show great potential for enhancing the production of n‐3 PUFA‐enriched TAG

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients.Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell’s concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape.Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients.Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses

Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.METHODS: To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4 + T-cell counts, HIV reservoir, and other clinical parameters. RESULTS: Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4 + T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4 + T-cell level. CONCLUSIONS: Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.</p

Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV

BackgroundPeople living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.MethodsTo test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4+ T-cell counts, HIV reservoir, and other clinical parameters.ResultsCompared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4+ T-cell–associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4+ T-cell level.ConclusionsOur findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV