Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study.

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.

Protocol for iron-catalyzed cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides.

Organochlorides are a crucial class of electrophiles in organic synthesis. Here, we present a protocol for the cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides, facilitated by an iron/B2pin2 catalytic system. We describe steps for the coupling of aryl chlorides with alkyl chlorides, followed by purification of products. This protocol can produce alkylated products with up to 81% yield. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.

Inchworm-like Soft Robot with Multi-Responsive Bilayer Films.

As an important branch of robotics, soft robots have the advantages of strong flexibility, a simple structure, and high safety. These characteristics enable soft robots to be widely used in various fields such as biomedicine, military reconnaissance, and micro space exploration. However, contemporary soft crawling robots still face problems such as the single drive mode and complex external equipment. In this study, we propose an innovative design of an inchworm-like soft crawling robot utilizing the synergistic interaction of electricity and moisture for its hybrid dual-drive locomotion. The legs of the soft robot are mainly made of GO-CNT/PE composite film, which can convert its own volume expansion into a corresponding bending motion after being stimulated by electricity or moisture. Unlike other drive methods, it requires less power and precision from external devices. The combination of the two driving methods greatly improves the environmental adaptability of the soft robot, and we developed visible light as the driving method on the basis of the dual drive. Finally, we also verified the robot's excellent load capacity, climbing ability, and optical drive effect, which laid the foundation for the application of soft robots in the future.

Symbolic iteration method based on computer algebra analysis for Kepler's equation.

The Kepler's equation of elliptic orbits is one of the most significant fundamental physical equations in Satellite Geodesy. This paper demonstrates symbolic iteration method based on computer algebra analysis (SICAA) to solve the Kepler's equation. The paper presents general symbolic formulas to compute the eccentric anomaly (E) without complex numerical iterative computation at run-time. This approach couples the Taylor series expansion with higher-order trigonometric function reductions during the symbolic iterative progress. Meanwhile, the relationship between our method and the traditional infinite series expansion solution is analyzed in this paper, obtaining a new truncation method of the series expansion solution for the Kepler's equation. We performed substantial tests on a modest laptop computer. Solutions for 1,002,001 pairs of (e, M) has been conducted. Compared with numerical iterative methods, 99.93% of all absolute errors δE of eccentric anomaly (E) obtained by our method is lower than machine precision [Formula: see text] over the entire interval. The results show that the accuracy is almost one order of magnitude higher than that of those methods (double precision). Besides, the simple codes make our method well-suited for a wide range of algebraic programming languages and computer hardware (GPU and so on).

Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome.

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1ß and IL-18 levels and repressed hepatic IL-1ß, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.

A novel Tembusu virus isolated from goslings in China form a new subgenotype 2.1.1.

Since 2010, several duck Tembusu viruses (DTMUVs) have been isolated from infected ducks in China, and these virus strains have undergone extensive variation over the years. Although the infection rate is high, the mortality rate is usually relatively low-~5%-30%; however, since fall 2019, an infectious disease similar to DTMUV infection but with a high mortality rate of ~50% in goslings has been prevalent in Anhui Province, China. The present study identified a new Tembusu virus, designated DTMUV/Goose/China/2019/AQ-19 (AQ-19), that is believed to be responsible for the noticeably high mortality in goslings. To investigate the genetic variation of this strain, its entire genome was sequenced and analysed for specific variations, and goslings and mice were challenged with the isolated virus to investigate its pathogenicity. The AQ-19 genome shared only 94.3%-96.9% and 90.9% nucleotide identity with other Chinese and Malaysian DTMUVs, respectively; however, AQ-19 has high homology with Thailand DTMUVs (97.2%-98.1% nucleotide identity). Phylogenetic analysis of the E gene revealed that AQ-19 and most of Thailand DTMUVs form a branch separate from any of the previously reported DTMUV strains in China. After the challenge, some goslings and mice showed typical clinical signs of DTMUV, particularly severe neurological dysfunction. AQ-19 has high virulence in goslings and mice, resulting in 60% and 70% mortality through intramuscular and intracerebral routes, respectively. Pathological examination revealed severe histological lesions in the brain and liver of the infected goslings and mice. Taken together, these results demonstrated the emergence of a novel Tembusu virus with high virulence circulating in goslings in China for the first time, and our findings highlight the high genetic diversity of DTMUVs in China. Further study of the pathogenicity and host range of this novel Tembusu virus is particularly important.

Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1α/GSTA1 expression via JNK signaling pathway.

Drug-induced liver injury (DILI) is a serious and frequently occurring issue in drug development. The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in many diseases; hepatocyte nuclear factor-1α (HNF-1α) and glutathione S-transferase A1 (GSTA1) are important in regulating liver-specific genes expressions and affecting drug metabolism. Oltipraz is used to treat liver cirrhosis by improving liver function, and C2-ceramide is a pro-apoptotic lipid that regulates multiple signaling pathways. In this study, we investigated the function of the JNK signaling pathway with HNF-1α and GSTA1 in a cellular model of DILI and whether oltipraz and C2-ceramide exert effects via the JNK pathway. The results showed that inhibiting JNK could ameliorate APAP-induced hepatocyte injury, reduced oxidative stress, suppressed JNK and c-Jun activation, and hepatocyte apoptosis. Meanwhile, the mRNA and protein expressions of HNF-1α and GSTA1 were increased significantly compared to control conditions. The effect of oltipraz (8 µmol/L) was similar to a JNK inhibitor and significantly increased HNF-1α/GSTA1 expression, but oltipraz combined with JNK inhibitor did not show a synergistic effect. Although C2-ceramide (8 µmol/L) aggravated hepatocyte injury and apoptosis, exacerbated oxidative stress, increased phosphorylation of JNK and c-Jun, and markedly decreased HNF-1α/GSTA1 expression, C2-ceramide combined with JNK inhibitor could partially alleviate these alterations. These results demonstrated that the JNK signaling pathway with HNF-1α/GSTA1 are involved in the process of DILI. Inhibiting JNK up-regulated HNF-1α and GSTA1 expressions which could attenuate hepatocyte injury. Oltipraz and C2-ceramide might affect the expression of HNF-1α/GSTA1 though JNK signaling.

Epigallocatechin-3-gallate exhibits antiviral effects against the duck Tembusu virus via blocking virus entry and upregulating type I interferons.

The duck Tembusu virus (DTMUV) is a novel mosquito-borne Flavivirus which caused huge economic losses for poultry industries in Southeast Asia and China. Currently, no effective antiviral drugs against this virus have been reported. (-)-Epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in green tea, has recently been demonstrated to have an antiviral activity for many viruses; however, whether EGCG can inhibit DTMUV infection remains unknown. Here, we tried to explore the anti-DTMUV effects and mechanisms of EGCG both in vitro and in vivo. Several EGCG treatment regimens were used to study the comprehensive antiviral activity of EGCG in DTMUV-infected baby hamster kidney cell line (BHK-21). The DTMUV titers of mock- and EGCG-treated infected cell cultures were determined using the tissue culture infective dose assay and the DTMUV mRNA copy number as determined using quantitative Real Time PCR. Moreover, the therapeutic efficacy of EGCG against DTMUV was assessed in DTMUV-infected ducklings. Our results suggested that EGCG significantly reduced the viral infection in BHK-21 cells in a dose-dependent manner, as reflected by the reduction of virus titers, virus copy number, and the expressions of viral E protein. We also observed that EGCG exhibited direct virucidal abilities against DTMUV. Notably, a significant reduction in virus binding ability was also observed, indicating that EGCG possesses excellent inhibitory effects on the viral adsorption step. In addition, DTMUV replication was also suppressed in BHK-21 cells treated with EGCG after viral entry, likely because of upregulation of the levels of interferon alfa and interferon beta. Finally, we also proved that EGCG exhibited anti-DTMUV efficacy in a duckling infection model because the survival rate was significantly improved. This is the first study to demonstrate the protective effect of EGCG against DTMUV, suggesting its potential use as an antiviral drug for DTMUV infection.

Validation and Diagnostic Performance of a CFD-Based Non-invasive Method for the Diagnosis of Aortic Coarctation.

Purpose: The clinical diagnosis of aorta coarctation (CoA) constitutes a challenge, which is usually tackled by applying the peak systolic pressure gradient (PSPG) method. Recent advances in computational fluid dynamics (CFD) have suggested that multi-detector computed tomography angiography (MDCTA)-based CFD can serve as a non-invasive PSPG measurement. The aim of this study was to validate a new CFD method that does not require any medical examination data other than MDCTA images for the diagnosis of CoA. Materials and methods: Our study included 65 pediatric patients (38 with CoA, and 27 without CoA). All patients underwent cardiac catheterization to confirm if they were suffering from CoA or any other congenital heart disease (CHD). A series of boundary conditions were specified and the simulated results were combined to obtain a stenosis pressure-flow curve. Subsequently, we built a prediction model and evaluated its predictive performance by considering the AUC of the ROC by 5-fold cross-validation. Results: The proposed MDCTA-based CFD method exhibited a good predictive performance in both the training and test sets (average AUC: 0.948 vs. 0.958; average accuracies: 0.881 vs. 0.877). It also had a higher predictive accuracy compared with the non-invasive criteria presented in the European Society of Cardiology (ESC) guidelines (average accuracies: 0.877 vs. 0.539). Conclusion: The new non-invasive CFD-based method presented in this work is a promising approach for the accurate diagnosis of CoA, and will likely benefit clinical decision-making.

Pressure-flow curve derived from coronary CT angiography for detection of significant hemodynamic stenosis.

OBJECTIVES: Coronary CT angiography (cCTA) has been used to non-invasively assess both the anatomical and hemodynamic significance of coronary stenosis. The current study investigated a new CFD-based method of evaluating pressure-flow curves across a stenosis to further enhance the diagnostic value of cCTA imaging. METHODS: Fifty-eight patients who underwent both cCTA imaging and invasive coronary angiography (ICA) with fractional flow reserve (FFR) within 2 weeks were enrolled. The pressure-flow curve-derived parameters, viscous friction (VF) and expansion loss (EL), were compared with conventional cCTA parameters including percent area stenosis (AS) and minimum lumen area (MLA) by receiver operating characteristic (ROC) curve analysis. FFR ≤ 0.80 was used to indicate ischemia-causing stenosis. Correlations between FFR and other measurements were calculated by Spearman's rank correlation coefficient (rho). RESULTS: Sixty-eight stenoses from 58 patients were analyzed. VF, EL, and AS were significantly larger in the group of FFR ≤ 0.8 while smaller MLA values were observed. The ROC-AUC of VF (0.91, 95% CI 0.81-0.96) was better than that of AS (change in AUC (ΔAUC) 0.27, p < 0.05) and MLA (ΔAUC 0.17, p < 0.05), and ROC-AUC of EL (0.90, 95%CI 0.80-0.96) was also better than that of AS (ΔAUC 0.26, p < 0.05) and MLA (ΔAUC 0.16, p < 0.05). FFR values correlated well with VF (rho = - 0.74 (95% CI - 0.83 to - 0.61, p < 0.0001) and EL (rho = - 0.74 (95% CI - 0.83 to - 0.61, p < 0.0001). CONCLUSION: Pressure-flow curve-derived parameters enhance the diagnostic value of cCTA examination. KEY POINTS: • Pressure-flow curve derived from cCTA can assess coronary lesion severity. • VF and EL are superior to cCTA alone for indicating ischemic lesions. • Pressure-flow curve derived from cCTA may assist in clinical decision-making.

Araneose Ti3+ self-doping TiO2/SiO2 nanowires membrane for removal of aqueous MB under visible light irradiation.

Araneose Ti3+ self-doped TiO2/SiO2 nanowires (RTiO2/SiO2) were prepared and anchored onto a polyethersulfone (PES) membrane. Careful characterizations and measurements indicated a covalent grafting of SiO2 onto reduced TiO2 (RTiO2) through Ti-O-Si linkages, acquiring uniformed RTiO2/SiO2 nanowires of almost complete anatase and benign hydrophilicity. The RTiO2/SiO2-based PES membrane showed a significantly enhanced visible light-driven degradation rate of methylene blue (MB) (90.7%), compared with that on bare PES (11.1%) and PES-RTiO2 (59.6%) membranes. The residual MB in filtered water was less than 5% after reusing three times. The normalized permeate flux of the modified membrane was 0.83, and the transmembrane pressure only increased by 0.4 MPa under irradiation of visible light. The improved performance of the PES-RTiO2/SiO2 was attributed to efficient intercept of MB molecular, light harvesting of visible light, and separation of charge carriers on araneose RTiO2/SiO2 nanowires.

Tributyltin disrupts feeding and energy metabolism in the goldfish (Carassius auratus).

Tributyltin (TBT) can induce obesogen response. However, little is known about the adverse effects of TBT on food intake and energy metabolism. The present study was designed to investigate the effects of TBT, at environmental concentrations of 2.44 and 24.4 ng/L (1 and 10 ng/L as Sn), on feeding and energy metabolism in goldfish (Carassius auratus). After exposure for 54 d, TBT increased the weight gain and food intake in fish. The patterns of brain neuropeptide genes expression were in line with potential orexigenic effects, with increased expression of neuropeptide Y and apelin, and decreased expression of pro-opiomelanocortin, ghrelin, cocaine and amphetamine-regulated transcript, and corticotropin-releasing factor. Interestingly, the energy metabolism indicators (oxygen consumption, ammonia exertion and swimming activity) and the serum thyroid hormones were all significantly increased at the 2.44 ng/L TBT group in fish. However, no changes of energy metabolism indicators or a decrease of thyroid hormones was found at the 24.4 ng/L TBT group, which indicated a complex disrupting effect on metabolism of TBT. In short, TBT can alter feeding and energy metabolism in fish, which might promote the obesogenic responses.

Fluorescence detection of DNA hybridization based on the aggregation-induced emission of a perylene-functionalized polymer.

A perylene-functionalized polycation was synthesized by quaternization of poly(4-vinylpyridine) with bromomethyl-perylene and methyl iodide, which exhibited a unique aggregation-induced emission (AIE) effect. The synthesized polycation and polyanion ssDNA could form a complex probe to detect DNA hybridization. Upon adding noncomplementary ssDNA, the fluorescence of the complex probe increased due to the AIE effect; upon adding complementary ssDNA, the fluorescence intensity changed little due to the combined effects of AIE and duplex-quenching resulting from the intercalation of perylene into the duplex.

Polymer nanoparticles for controlled release stimulated by visible light and pH.

Polymer nanoparticles are prepared by self-assembly of visible light and pH sensitive perylene-functionalized copolymers which are synthesized by quaternization between 1-(bromomethyl)perylene and the dimethylaminoethyl units of poly(dimethylaminoethyl methacrylate) (PDMAEMA). The perylene-containing polymethacrylate segments afford the system visible light responsiveness and the unquaternized PDMAEMA segments afford the system pH responsiveness. The self-assembled nanoparticles exhibit a unique dual stimuli response. They can be photocleaved under visible light irradiation, shrunken to smaller nanoparticles at high pH, and swollen at low pH. The structural change endows the nanoparticle with great potential as a sensitive nanocarrier for controlled release of Nile Red and lysozyme under this stimulation. The visible light responsiveness and synergistic effect on the release of loaded molecules with the dual stimulation may obviate the need for harsh conditions such as UV light or extreme pH stimulation, rendering the system more applicable under mild conditions.

Label-Free DNA Sequence Detection through FRET from a Fluorescent Polymer with Pyrene Excimer to SG.

A label-free complex probe composed of a water-soluble fluorescent pyrene-functionalized polymer, ssDNA, and a nucleic acid stain (SG) is presented here, which can detect DNA sequence via FRET from pyrene excimer to SG. Complementary and one-base mismatched strands at nanomolar concentrations can be distinguished by the examination of the FRET fluorescence intensity of SG. This novel strategy for detecting DNA using the fluorescent pyrene-functionalized polymer not only affords a simple label-free method to detect nucleic acid sequence but also endows the detection with high sensitivity and selectivity, which may find wide applications for optical biosensing.

[Study on the hepatoxicity of polygoni multiflori radix and polygoni multiflori rodix praeparata in rats].

OBJECTIVE: To compare the hepatoxicity of Polygoni Multiflori Radix and Polygoni Multiflori Rodix Praeparata in rats. METHODS: Water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Rodix Praeparata were prepared by concentional decocting method (named as RPWE and PPWE respectively). Both in 30 days and 60 days experiments, SD rats were randomly divided into 5 groups: normal control group, RPWE high dosage group (40 mg/kg x d) and PPWE low dosage group (20 mg/kg x d), PPWE high dosage group (40 mg/kg x d) and PPEW low dosage group (20 mg/kg x d). After daily administration,the general conditions of rats were observed. At the end of the experiments, the levels of ALT and AST in plasma were detected. The liver coefficient was calculated and HE staining was used to observe the changes of liver tissue sections. RESULTS: Both in 30 days and 60 days experiments, the treatment groups rats had hypokinesia and dry fur when compared with control groups, and in a dose-dependent manner. The liver coefficients, levels of ALT and AST of plasma weren't changed significantly when conpared with control groups. The liver had varying degrees of steatosis and inflammation cell infiltration in the treatment groups rats in 60 days experiment. CONCLUSION: Oral administration of Polygoni Multiflori Radix and Polygoni Multiflori Rodix Praeparata for 60 days have hepatoxic in rats.

Synthesis and fluorescence study of a quaternized copolymer containing pyrene for DNA-hybridization detection.

Built-in detector: A quaternized copolymer containing pyrene is described, which can bind to single-stranded DNA by electrostatic interactions to form a novel complex probe for the detection of DNA hybridization through strengthened fluorescence quenching through its intercalation into double-stranded DNA (see figure).

[Damage effect of Polygonum multiflorum fractions on human normal liver cells L02 and liver cancer cells HepG2].

OBJECTIVE: To investigate the damage effect of different fractions from Polygonum multiflorum on normal human liver and liver cancer cells, in order to seek for fractions that can obviously kill cancer cells but have less impact on normal liver cells, and make a preliminary study on different mechanism of the two kinds of cells. METHOD: P. multiflorum water-eluted fraction (RW), 50% ethanol-eluted fraction (R50) and 95% ethanol-eluted fraction (R95) were successively obtained from 70% ethanol extracts of P. multiflorum, after being eluted by water, 50% ethanol and 95% ethanol and then absorbed by AB-8 macroporous resin. Normal human liver L02 cells and liver cancer HepG2 cells were incubated with cell supernatants from different fractions and cells. MTT method and inverted microscope were adopted to observe the impact of L02 on growth of HepG2 cells, screening fractions with damage effect and detect their doses and time effect. Giemsa stain showed changes in cell nucleus after administration and flow cytometry analysis was used to detect cycle and apoptosis of L02 cells. RESULT: MTT method and inverted microscope showed that R50 had significant growth inhibition effects on L02 and HepG2 cells. According to giemsa stain and flow cytometry analysis, R50 showed different effect on inducing the two cells: there are much more apoptotic HepG2 cells than apoptotic L02 cells in each time phase (the proportion of the apoptosis cells in HepG2 group were 83.62%, 60.52% and 74.49%, and ID2 31.02%, 20.57% and 25.32% after treated with R50 for 24, 48, 72 h. Both cells showed less than 5% of apoptotic cells in the negative control group in each time phase). However, there is no significant impact on cycle of both cells. CONCLUSION: R50 from P. multiflorum extracts had different damage effects on human liver L02 cells and liver cancer HepG2 cells, which was caused by different degree of induction on apoptosis of the two cells in nature.