The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been ...systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.
Background and Purpose
Although increasing evidence illustrated that the bidirectional communication between the brain and the gut is closely related to the occurrence of various complex diseases. ...Limited effort has been made to explore the influence of intestinal flora on the risk of ischaemic stroke. The present study aims to identify microbiota and specialized microbiota metabolites related to the occurrence and treatment of ischaemic stroke.
Experimental Approach
The role of microbiota in the occurrence and the treatment of ischaemic stroke was evaluated on ischaemia/reperfusion (I/R), pseudo‐germ‐free and faecal transplantation animals. The target microbiota and specialized metabolites were identified by comparing their distribution in flora and metabolomic profiles in ischaemic stroke patients and animals with compared with healthy controls. The effects and mechanisms involved of the targeted metabolites in ischaemic stroke were explored in ischaemia/reperfusion rats, hypoxia/reoxygenation PC12 cells and LPS‐induced inflammatory BV2 cells.
Key Results
Both ischaemic stroke patients and I/R rats had significant accumulation of branched‐chain amino acids, which were closely associated with gut microflora dysbiosis and the development of ischaemic stroke. Lactobacillus helveticus (L.hel) and Lactobacillus brevis (L.bre) are identified as the microbiota most affected by ischaemia/reperfusion modelling and treatment. L.hel and L.bre colonization exhibited significant neuroprotective activity and could greatly alleviate the accumulation of branched‐chain amino acids. In addition, branched‐chain amino acid (BCAA) accumulation was shown to exacerbate microglia‐induced neuroinflammation by activating AKT/STAT3/NF‐κB signalling.
Conclusion and Implications
Our findings demonstrated the crucial role of intestinal flora and microbiota metabolites in the occurrence and treatment of ischaemic stroke.
Summary
The continuing nitrogen (N) deposition observed worldwide alters ecosystem nutrient cycling and ecosystem functioning. Litter decomposition is a key process contributing to these changes, but ...the numerous mechanisms for altered decomposition remain poorly identified.
We assessed these different mechanisms with a decomposition experiment using litter from four abundant species (Achnatherum sibiricum, Agropyron cristatum, Leymus chinensis and Stipa grandis) and litter mixtures representing treatment‐specific community composition in a semi‐arid grassland under long‐term simulation of six different rates of N deposition.
Decomposition increased consistently with increasing rates of N addition in all litter types. Higher soil manganese (Mn) availability, which apparently was a consequence of N addition‐induced lower soil pH, was the most important factor for faster decomposition. Soil C : N ratios were lower with N addition that subsequently led to markedly higher bacterial to fungal ratios, which also stimulated litter decomposition.
Several factors contributed jointly to higher rates of litter decomposition in response to N deposition. Shifts in plant species composition and litter quality played a minor role compared to N‐driven reductions in soil pH and C : N, which increased soil Mn availability and altered microbial community structure. The soil‐driven effect on decomposition reported here may have long‐lasting impacts on nutrient cycling, soil organic matter dynamics and ecosystem functioning.
There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a ...multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of
Murr (Huaier granule) to address this unmet need.
A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively.
This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.
NCT01770431; Post-results.
This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in ...patients with hepatocellular carcinoma (HCC).
One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch™ System.
Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC < 2 to postoperative CTC ≥ 2) had significantly shorter disease-free survival (DFS) and overall survival (OS) than did patients with persistent CTC < 2. Patients with persistent CTC levels of ≥2 had the worst prognoses.
Surgical liver resection is associated with an increase in CTC counts, and increased postoperative CTC numbers are associated with a worse prognosis in patients with HCC.
Development of a solar water splitting device requires design of a low‐cost, efficient, and non‐noble metal compound as alternative to noble metals. For the first time, we showed that CoSe2 can ...function as co‐catalyst in phototoelectrochemical hydrogen production. We designed a heterostructure of p‐Si and marcasite‐type CoSe2 for solar‐driven hydrogen production. CoSe2 successively coupled with p‐Si can act as a superior photocathode in the solar‐driven water splitting reaction. Photocurrents up to 9 mA cm−2 were achieved at 0 V vs. reversible hydrogen electrode. Electrochemical impedance spectroscopy showed that the high photocurrents can be attributed to low charge transfer resistance between the Si and CoSe2 interfaces and that between the CoSe2 and electrolyte interfaces. Our results suggest that this CoSe2 is a promising alternative co‐catalyst for hydrogen evolution.
Heterostructures of semi‐metallic CoSe2 nanorods and p‐Si microwires behave as an efficient photocathode for the solar‐driven hydrogen evolution reaction. Photocurrents as high as 9 mA cm−2 have been achieved at 0 V vs. reversible hydrogen electrode. The high photocurrents can be attributed to low charge transfer resistance between the Si and CoSe2 interfaces and between the CoSe2 and electrolyte interfaces.
Background
Spontaneous tumor rupture is a rare and life-threatening complication of hepatocellular carcinoma (HCC). The best treatment strategy remains unclear.
Methods
The clinical data of 137 ...patients with spontaneously ruptured HCC from 2010 to 2015 were reviewed retrospectively. We investigated the outcome and prognostic factors of various treatment strategies.
Results
Of the 137 patients, 53, 45, 3, and 36 patients underwent transcatheter arterial chemoembolization (TACE) alone, liver resection (LR) (LR alone or TACE + LR), surgical hemostasis, and conservative therapy. The patients undergoing LR had longest overall survival (OS). In the TACE alone group, independent factors affecting 30-day mortality were MELD score ≥ 12, AFP ≥ 1000 ng/ml, and largest tumor size ≥ 10 cm. AFP ≥ 1000 ng/ml, largest tumor size ≥ 10 cm, and no tumor capsule were significantly associated with poorer OS. In the LR group, largest tumor size ≥ 10 cm and no tumor capsule were the only independent prognostic factors for poorer OS and recurrence-free survival (RFS). Hypovolemic shock was an independent prognostic factor for poorer OS. The differences in OS between the TACE + LR group and LR alone group were not significant (
P
= 0.955). However, the RFS is significantly better in the LR alone group than those in the TACE + LR group (
P
= 0.031).
Conclusion
For resectable tumor, LR is the treatment of choice for patients with spontaneous ruptured HCC and preserved liver function. The delay in LR due to preoperative TACE may account for its worse RFS compared with LR alone. In patients with an unresectable tumor, TACE therapy alone improved survival over conservative therapy.
Renal interstitial fibrosis (RIF) is a common manifestation of inflammatory and noninflammatory renal diseases, which correlates to renal excretory dysfunction. Recently, the long noncoding RNAs ...(lncRNAs) have been demonstrated to be involved in the development of various renal diseases. Here, we aim to determine whether paeonol (PAE) affects RIF with involvement of the lncRNA HOX transcript antisense intergenic RNA (HOTAIR)/microRNA‐124 (miR‐124)/Notch1 axis. RIF rat models were established by performing unilateral ureteral occlusion (UUO), in which interactions between HOTAIR, Notch1, and miR‐124 were determined. To identify the roles of PAE and HOTAIR in RIF, rats were injected with HOTAIR or PAE. Subsequently, to further investigate the underlying mechanism of PAE in RIF, epithelial to mesenchymal transition (EMT)‐ and migration‐related genes in NRK‐49F cells were measured. Next, rats were further treated with IMR‐1 (inhibitor of the Notch1/Jagged1 signaling pathway) to determine how PAE influences the Notch1/Jagged1 signaling pathway. HOTAIR interacted with miR‐124, and miR‐124 directly targeted Notch1, and HOTAIR was observed to be upregulated in RIF rats. PAE was found to decrease HOTAIR and Notch1 expression but to increase the miR‐124 expression in RIF rats. PAE inhibited EMT and migration of NRK‐49F cells facilitated by HOTAIR. HOTAIR activated the Notch1/Jagged1 signaling pathway by downregulating miR‐124, while PAE reversed these effects of HOTAIR on the Notch1/Jagged1 signaling pathway. Overall, our study demonstrates the contributory effect of lncRNA HOTAIR on RIF by activating the Notch1/Jagged1 signaling pathway via inhibition of miR‐124, whereas administration of PAE can alleviate the effects of HOTAIR on RIF.
Our study demonstrates the contributory effect of long noncoding RNA HOTAIR on RIF by activating the Notch1/Jagged1 signaling pathway via inhibition of miR‐124, whereas administration of PAE can alleviate the effects of HOTAIR on renal interstitial fibrosis.
Carrier phase measurements currently play a crucial role in achieving rapid and highly accurate positioning of global navigation satellite systems (GNSS). Resolving the integer ambiguity correctly is ...one of the key steps in this process. To address the inefficiency and slow search problem during ambiguity solving, we propose a single-frequency GNSS integer ambiguity solving based on an adaptive genetic particle swarm optimization (AGPSO) algorithm. Initially, we solve for the floating-point solution and its corresponding covariance matrix using the carrier-phase double difference equation. Subsequently, we decorrelate it using the inverse integer Cholesky algorithm. Furthermore, we introduce an improved fitness function to enhance convergence and search performance. Finally, we combine a particle swarm optimization algorithm with adaptive weights to conduct an integer ambiguity search, where each generation selectively undergoes half-random crossover and mutation operations to facilitate escaping local optima. Comparative studies against traditional algorithms and other intelligent algorithms demonstrate that the AGPSO algorithm exhibits faster convergence rates, improved stability in integer ambiguity search results, and in practical experiments the baseline accuracy of the solution is within 0.02 m, which has some application value in the practical situation of short baselines.
Phenotypic switching between tachyzoite and bradyzoite is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Although accumulation ...of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage, the regulatory factors and mechanisms contributing to amylopectin storage in bradyzoites are incompletely known. Here, we show that T. gondii protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit PP2A-C, a scaffold subunit PP2A-A and a regulatory subunit PP2A-B. Disruption of any of these subunits increased starch accumulation and blocked the tachyzoite-to-bradyzoite differentiation. PP2A contributes to the regulation of amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 at S679. Phosphoproteomics identified several putative PP2A holoenzyme substrates that are involved in bradyzoite differentiation. Our findings provide novel insight into the role of PP2A as a key regulator of starch metabolism and bradyzoite differentiation in T. gondii.
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