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Our previous studies have shown that activating α7nAChRs suppresses systemic inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP) in early sepsis. Now that the medullary visceral zone (MVZ) is the center of CAP and responsible for regulating systemic inflammation, what changes will occur in MVZ’s pathology and function in sepsis, especially when interfering with α7nAChRs? Does activation of MVZ’s α7nAChRs contribute to the inhibition of systemic inflammation? To clarify these issues, we explored the systemic inflammation and immunity state by detecting serum levels of TNF-α, IL-6, HMGB1, sCD14, and CD4+CD25+Treg and TH17 lymphocytes percentage, meanwhile, we analyzed the apoptosis of cholinergic and catecholaminergic neurons and the expressions of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) in MVZ in sepsis and the interfering effects on α7nAChRs. In this study, we found that in sepsis, serum TNF-α, IL-6, HMGB1, sCD14, CD4+CD25+Treg, and TH17 lymphocytes significantly increased and the ratio of Treg/TH17 significantly decreased, cholinergic and catecholaminergic neurons underwent apoptosis with low expressions of TH and CHAT in MVZ; activation of α7nAChRs not only significantly decreased the levels of septic serum TNF-α, IL-6, HMGB1, sCD14, and TH17 lymphocytes (P ＜ 0.05), but also significantly reduced cholinergic and catecholaminergic neurons’ apoptosis, and promoted expressions of TH/CHAT. Our study reveals that sepsis undermines MVZ through neuroinflammation which contributes to the uncontrolled systemic inflammation. Activating central α7nAChRs is not only helpful to restore MVZ’s structure and function but also beneficial to subside the inflammatory storm in sepsis. Even if MVZ is damaged in sepsis, cholinergic neurons in MVZ still regulate the systemic inflammation stably.

The objective of this study was to investigate the effect of modified Dioscorea pills (MDP) on microcirculatory remodeling in the hippocampus of rats with chronic cerebral hypoperfusion (CCH) through the angiopoietin (Ang)/tyrosine kinase receptor tyrosine kinase with immunoglobulin-like and EGF-like domains (Ang receptor) 2 (Tie-2) signaling pathways, which may underlie the cognitive improvement observed in CCH rats.

BACKGROUND: Water and nutrients are two main determinants of wheat yield, which are vital for maintaining high crop yields. In the present study, the effects of water and phosphate fertilization on wheat yield, photosynthetic parameters, water productivity and phosphate use efficiency were investigated. Five dryland wheat cultivars from the 1940s to the 2010s that are widely cultivated in Shaanxi Province, China, were used. Experiments were conducted from 2019 to 2022 using two irrigation levels (normal rainfall and no precipitation after the reviving stage) and two phosphorus application levels (0 and 100 kg ha−1). RESULTS: Compared with old cultivars ('Mazha'), the grain yield of modern cultivars ('Changhan 58') was 89.24% higher and was closely correlated with chlorophyll index, leaf area index, photosynthetic rate and tillers. With the replacement of cultivars, the phosphorus content, water potential and phosphatase activity of wheat leaves increased. Considering water–phosphorus interactions, the water use efficiency and phosphorus use efficiency of wheat showed a significant positive correlation. CONCLUSION: Our findings indicate that modern wheat cultivars are more responsive to phosphorus. Further analysis revealed that modern varieties have evolved two phosphorus absorption strategies in response to phosphorus deficiency – namely, the formation of a phosphorus supply source, which may result in larger numbers of green organs; and an increase in phosphorus sinks, which tended to activation and transport of plant phosphorus. Our results may thus contribute to water conservation, increased yields and the development of strategies for efficient phosphorus fertilization. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Estimation of the porosity of a hydrate reservoir is essential for its exploration and development. However, the estimation accuracy was usually less certain in most previous studies that simply assumed that there is a linear relationship between the porosity and single‐elastic wave velocities or other rock physical parameters, thus affecting the evaluation of the reserves. In the three‐phase Biot‐type equations that are fundamental to model a hydrate‐bearing reservoir, porosity, alongside hydrate saturation, mineral constituent proportions and hydrate–grain contact factor, is non‐linearly responded by density, compressional and shear wave velocities. To improve porosity estimation, we propose to invert simultaneously four‐parameter (porosity, hydrate saturation, mineral constituent proportions and hydrate–grain contact factor) using an iteratively nonlinear interior‐point optimization algorithm to solve a nonlinear objective function that is a summation of the squared misfits between the well log and three‐phase Biot‐type equation–modelled density, compressional and shear wave velocities. A test in Mount Elbert gas hydrate research well was conducted for the case of a gas hydrate stratigraphic test well where elastic wave velocities, density, porosity and mineral composition analysis data are available. The four‐parameter inversion yielded a lower root mean square error for porosity (0.0245) across the entire well‐logging section compared to previous estimations from the linear relationship, post‐stacked and pre‐stacked seismic traces as well as the pore‐filling effective medium theory model applied to other well cases. Additionally, the other three parameters demonstrated good agreement with well logs. Inversion tests conducted at three additional hydrate sites also produced accurate results. Consequently, the new method surpasses previous approaches in porosity estimation accuracy. [ABSTRACT FROM AUTHOR]

Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO‐induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF. [ABSTRACT FROM AUTHOR]