Sepsis is the leading course of morbidity and mortality in critically ill patients. This study aimed to evaluate the predictive value of the platelet aggregation for mortality in patients with sepsis. In addition, the relationship between impaired mitochondria and the platelet aggregation was explored. This was a prospective, observational cohort study. The platelet aggregation rate in response to adenosine diphosphate (ADP) was assessed. The primary outcome was 28-day mortality. Platelet mitochondrial parameters, including adenosine triphosphate(ATP), mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening, were measured. Platelet mitochondrial ultrastructure was observed using transmission electron microscopy. 86 patients with 65 survivors and 21 non-survivors were enrolled. Platelets of non-survivors with sepsis were hyporesponsive to ADP, in terms of maximal aggregation rate (P < 0.001). Receiver operating characteristic curves analysis demonstrated that the AUC estimated 28-day mortality for platelet aggregation rate was 0.814. At the optimal cut-off value of 35.8% for platelet aggregation rate, the sensitivity was 86.2% and the specificity was 66.7%. Kaplan-Meier analysis showed that a platelet aggregation rate of less than 35.8% was associated closely with poor survival. After adjusting for lactate by Cox regression analysis, platelet aggregation rate was identified as an independent predictor for the probability of 28-day mortality. Compared with survivors, non-survivors showed a significant reduction in platelet ATP and MMP-index (both P < 0.001), and a remarkable increase in mPTP opening (P < 0.001). ATP and MMP-index were positively correlated with platelet aggregation rate (R square=0.75, R square=0.44, respectively). Platelet aggregation rate could be an early predictive biomarker for mortality in sepsis. Impaired platelet mitochondrial activity affects platelet aggregation and correlates with the severity of sepsis.

A magnetically recoverable biocatalyst has been effectively prepared through the immobilization of α-amylase onto the Fe₃O₄ nanoparticles. The magnetic nanoparticles (MNPs) were synthesized by a sol–gel method in an aqueous system. The MNPs’ surfaces were modified with sodium silicate and 3-aminopropyltriethoxysilane (APTS). The adsorptive immobilization of α-amylase was attempted onto the APTS–SiO₂–Fe₃O₄ nanoparticles. The physicochemical properties of the biocatalysts were characterized with Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD) and thermal gravimetric analysis (TGA). The magnetic properties of the biocatalyst were analyzed by a vibrating sample magnetometer (VSM). The activity of free and immobilized α-amylase was also evaluated by direct measurement of the absorbance of starch solution at 620 nm using UV-vis spectrophotometry. The prepared particles exhibited superparamagnetic behavior at room temperature. The mass saturation magnetization (M_s) of the bare Fe₃O₄ nanoparticles and the biocatalyst was 175.7 and 50.4 emu g⁻¹ respectively. A biocatalyst was produced with a loading capacity of α-amylase of about 235 mg g⁻¹. The enzymatic activity of the immobilized enzyme was 882 U g⁻¹ which is about 79.53% of the free enzyme activity when not involved in the immobilized system. The immobilized enzyme exhibited significant thermal stability (stable up to 70 °C) and good durability (recycled 3 times without any obvious loss of enzymatic activity). This synthetic method provides a possible industrial route for the use of enzyme catalysts which eliminate the high operational costs and complicated recycle/reuse problems in the conventional enzyme catalysis process.

Objective: Sepsis is a life-threatening condition secondary to infection that evolves into a dysregulated host response and is associated with acute organ dysfunction. Sepsis-induced cardiac dysfunction is one of the most complex organ failures to characterize. This study performed comprehensive metabolomic profiling that distinguished between septic patients with and without cardiac dysfunction.Method: Plasma samples collected from 80 septic patients were analysed by untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics. Principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA), and orthogonal partial least square discriminant analysis (OPLS-DA) were applied to analyse the metabolic model between septic patients with and without cardiac dysfunction. The screening criteria for potential candidate metabolites were as follows: variable importance in the projection (VIP) >1, P < 0.05, and fold change (FC) > 1.5 or < 0.7. Pathway enrichment analysis further revealed associated metabolic pathways. In addition, we constructed a subgroup metabolic analysis between the survivors and non-survivors according to 28-day mortality in the cardiac dysfunction group.Results: Two metabolite markers, kynurenic acid and gluconolactone, could distinguish the cardiac dysfunction group from the normal cardiac function group. Two metabolites, kynurenic acid and galactitol, could distinguish survivors and non-survivors in the subgroup analysis. Kynurenic acid is a common differential metabolite that could be used as a candidate for both diagnosis and prognosis for septic patients with cardiac dysfunction. The main associated pathways were amino acid metabolism, glucose metabolism and bile acid metabolism.Conclusion: Metabolomic technology could be a promising approach for identifying diagnostic and prognostic biomarkers of sepsis-induced cardiac dysfunction.

: The intestine is one of the main target organs involved in the pathological process of heatstroke. CCAAT/enhancer-binding protein homologous protein (CHOP) is involved in endoplasmic reticulum (ER) stress-induced apoptosis. This study aimed to explore the role of CHOP in heatstroke-induced intestinal injury and potential therapy. An in vitro heat stress (HS) model using Caco-2 cells was employed. We observed the role of CHOP in apoptosis-mediated intestinal epithelial cell injury secondary to HS by evaluating cell viability, lactate dehydrogenase release, apoptosis levels, and GRP78, PERK, ATF4, CHOP, Bcl-2, and BAX mRNA and protein expression. To further study the role of CHOP in HS-induced intestinal barrier dysfunction, we assessed transepithelial electrical resistance, paracellular tracer flux, ultrastructure of tight junctions, and protein expression of ZO-1 and occludin. Male wild-type mice and CHOP knockout mice were used for in vivo experiments. We evaluated serum d-lactate and diamine oxidase levels, histopathological changes, intestinal ultrastructure, and ZO-1 and occludin protein expression. HS activated the PERK-CHOP pathway and promoted apoptosis by upregulating BAX and downregulating Bcl-2; these effects were prevented by CHOP silencing. Intestinal epithelial barrier function was disrupted by HS in vitro and in vivo. CHOP silencing prevented intestinal barrier dysfunction in Caco-2 cells, whereas CHOP knockout mice exhibited decreased intestinal mucosal injury. The ER stress inhibitor 4-phenylbutyrate (4-PBA) prevented HS-induced intestinal injury in vitro and in vivo. This study indicated that CHOP deficiency attenuates heatstroke-induced intestinal injury and may contribute to the identification of a novel therapy against heatstroke associated with the ER stress pathway.