Surface modification of Co3O4 nanosheets through Cd-doping for enhanced CO sensing performance.

The detection of hazardous CO gas is an important research content in the domain of the Internet of Things (IoT). Herein, we introduced a facile metal-organic frameworks (MOFs)-templated strategy to synthesize Cd-doped Co3O4 nanosheets (Cd-Co3O4 NSs) aimed at boosting the CO-sensing performance. The synthesized Cd-Co3O4 NSs feature a multihole nanomeshes structure and a large specific surface area (106.579 m2·g-1), which endows the sensing materials with favorable gas diffusion and interaction ability. Furthermore, compared with unadulterated Co3O4, the 2 mol % Cd-doped Co3O4 (2% Cd-Co3O4) sensor exhibits enhanced sensitivity (244%) to 100 ppm CO at 200 °C and a comparatively low experimental limit of detection (0.5 ppm/experimental value). The 2% Cd-Co3O4 NSs show good selectivity, reproducibility, and long-term stability. The improved CO sensitivity signal is probably owing to the stable nanomeshes construction, high surface area, and rich oxygen vacancies caused by cadmium doping. This study presents a facile avenue to promote the sensing performance of p-type metal oxide semiconductors by enhancing the surface activity of Co3O4 combined with morphology control and component regulation.

Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

Analysis of fecal microbiota and related clinical indicators in ICU patients with sepsis.

Background: To analyze the characteristics of fecal microbiota disturbance in the intensive care unit (ICU) patients with sepsis and the correlation with related clinical indicators. Methods: This study included 31 patients with sepsis admitted to the emergency ICU ward between September 2019 and December 2021. They were divided into Group without septic shock (ND_NS group, 7 cases) and Group with septic shock (ND_S group, 24 cases) according to the presence or absence of septic shock. Furthermore, we divided these 31 sepsis patients into Clinical Improvement group (21 cases) and Death or DAMA group (10 cases) based on clinical outcome, 15 cases of Physical Examiner recruited in the same period were included as control group: ND_HC group (15 cases). The fecal samples of the patients with sepsis within 24 h of admission and random fecal samples of the control group were collected and analyzed by 16S rDNA gene sequencing used for the analysis of fecal microbiota. At the same time, the relevant clinical data of these patients with sepsis were also collected for analysis. Results: There were 15 cases with drug-resistant bacteria in the ND_S group and only 2 cases in the ND_NS group (P = 0.015). There were significant differences in APACHE II score, length of ICU stay, lactate level, and oxygenation index of patients between the Death or DAMA group and Clinical Improvement group (all P < 0.05). For phylum level, the abundance of Firmicutes, Actinobacteria, and Bacteroidetes decreased in the ND group compared with the ND_HC group, while the abundance of Proteobacteria increased (P < 0.05). For genus level, the relative abundance of Escherichia-Shigella and Klebsiella were significantly increased in the ND group compared with the ND_HC group (P < 0.05). The top six genera in relative abundance in the ND_S group were Escherichia-Shigella, Enterococcus, Bifidobacterium, Lactobacillus, Akkermansia, and Klebsiella. Compared with the Clinical Improvement group, the relative abundance of Escherichia-Shigella and Klebsiella in the Death or DAMA group showed an increasing trend with no significant significance, while the relative abundance of Enterococcus and Faecalibacterium decreased in the Death or DAMA group (P < 0.05). Alpha diversity analysis showed that compared with the ND_HC group, the alpha diversity of the fecal microbiota in the ND group decreased. There were significant differences in the Observed_species index, Chao1 index, and ACE index of patients between the ND_HC group and ND group (all P < 0.05). Moreover, compared with the ND_NS group, the Alpha diversity of the ND_S group was more abundant. PCoA analysis showed significant differences in microbial community structure between the ND group and ND_HC group (P = 0.001). There also were significant differences in microbial community structure between the ND_S group and ND_NS group (P = 0.008). LEfSe analysis showed that compared with the ND_HC group, there were significant differences in the species of the ND group, including Enterobacteriaceae, Escherichia-Shigella, Enterococcus, Elizabethkingia, and Family_XIII_AD3011_group. Conclusions: ICU patients with sepsis suffered intestinal microecological disturbances with significantly decreased abundance of fecal microbiota, diversity, and beneficial symbiotic bacteria. For these patients, the ratio of pathogenic bacteria, including Escherichia-Shigella and Klebsiella increased and became the main bacterial genus in some samples. Moreover, the increasing trend of these two pathogenic bacteria may be correlated with the development of septic shock and the risk of death in patients with sepsis.

Few-Shot Relation Extraction With Automatically Generated Prompts.

Relation extraction (RE) tends to struggle when the supervised training data is few and difficult to be collected. In this article, we elicit relational and factual knowledge from large pretrained language models (PLMs) for few-shot RE (FSRE) with prompting techniques. Concretely, we automatically generate a diverse set of natural language templates and modulate PLM's behavior through these prompts for FSRE. To mitigate the template bias which leads to unstableness of few-shot learning, we propose a simple yet effective template regularization network (TRN) to prevent deep networks from over-fitting uncertain templates and thus stabilize the FSRE models. TRN alleviates the template bias with three mechanisms: 1) an attention mechanism over mini-batch to weight each template; 2) a ranking regularization mechanism to regularize the attention weights and constrain the importance of uncertain templates; and 3) a template calibration module with two calibrating techniques to modify the uncertain templates in the lowest-ranked group. Experimental results on two benchmark datasets (i.e., FewRel and NYT) show that our model has robust superiority over strong competitors. For reproducibility, we will release our code and data upon the publication of this article.

Combined exposure to multiple metals on abdominal aortic calcification: results from the NHANES study.

Exposure to metals increases the risk of many diseases and has become a public health concern. However, few studies have focused on the effect of metal on abdominal aortic calcification (AAC), especially the combined effects of metal mixtures. In this study, we aim to investigate the combined effect of metals on AAC risk and determine the key components in the multiple metals. We tried to investigate the relationship between multiple metal exposure and AAC risk. Fourteen urinary metals were analyzed with five statistical models as follows: generalized linear regression, weighted quantile sum regression (WQS), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) models. A total of 838 participants were involved, of whom 241 (28.8%) had AAC. After adjusting for covariates, in multiple metal exposure logistic regression, cadmium (Cd) (OR = 1.364, 95% CI = 1.035-1.797) was positively associated with AAC risk, while cobalt (Co) (OR = 0.631, 95% CI = 0.438-0.908) was negatively associated with AAC risk. A significant positive effect between multiple metal exposure and AAC risk was observed in WQS (OR = 2.090; 95% CI = 1.280-3.420, P < 0.01), Qgcomp (OR = 1.522, 95% CI = 1.012-2.290, P < 0.05), and BKMR models. It was found that the positive association may be driven primarily by Cd, lead (Pb), uranium (U), and tungsten (W). Subgroups analysis showed the association was more significant in participants with BMI ≥ 25 kg/m2, abdominal obesity, drinking, and smoking. Our study shows that exposure to multiple metals increases the risk of AAC in adults aged ≥ 40 years in the USA and that Cd, Pb, U, and W are the main contributors. The association is stronger in participants who are obese, smoker, or drinker.

[Analysis of NF1 gene variants in a Chinese pedigree and a sporadic patient with Neurofibromatosis type 1].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree and a sporadic case with Neurofibromatosis type 1 (NF1). METHODS: Clinical data of the pedigree and the sporadic case were collected. Genomic DNA was extracted from peripheral venous blood samples and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: All patients from the pedigree were found to harbor a c.3251delC variant in exon 25 of the NF1 gene, whilst a c.4312_4314delGAA variant was found in exon 32 of the NF1 gene in the sporadic case. CONCLUSION: Variants of the NF1 gene may account for the occurrence of NF1 in this pedigree and sporadic case.

PLEKHM2 deficiency induces impaired mitochondrial clearance and elevated ROS levels in human iPSC-derived cardiomyocytes.

Pleckstrin homology domain-containing family M member 2 (PLEKHM2) is an essential adaptor for lysosomal trafficking and its homozygous truncation have been reported to cause early onset dilated cardiomyopathy (DCM). However, the molecular mechanism of PLEKHM2 deficiency in DCM pathogenesis and progression is poorly understood. Here, we generated an in vitro model of PLEKHM2 knockout (KO) induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the potential pathogenic mechanism of PLEKHM2-deficient cardiomyopathy. PLEKHM2-KO hiPSC-CMs developed disease phenotypes with reduced contractility and impaired calcium handling. Subsequent RNA sequencing (RNA-seq) analysis revealed altered expression of genes involved in mitochondrial function, autophagy and apoptosis in PLEKHM2-KO hiPSC-CMs. Further molecular experiments confirmed PLEKHM2 deficiency impaired autophagy and resulted in accumulation of damaged mitochondria, which triggered increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (Δψm). Importantly, the elevated ROS levels caused oxidative stress-induced damage to nearby healthy mitochondria, resulting in extensive Δψm destabilization, and ultimately leading to impaired mitochondrial function and myocardial contractility. Moreover, ROS inhibition attenuated oxidative stress-induced mitochondrial damage, thereby partially rescued PLEKHM2 deficiency-induced disease phenotypes. Remarkably, PLEKHM2-WT overexpression restored autophagic flux and rescued mitochondrial function and myocardial contractility in PLEKHM2-KO hiPSC-CMs. Taken together, these results suggested that impaired mitochondrial clearance and increased ROS levels play important roles in PLEKHM2-deficient cardiomyopathy, and PLEKHM2-WT overexpression can improve mitochondrial function and rescue PLEKHM2-deficient cardiomyopathy.

Oxidized DJ-1 activates the p-IKK/NF-κB/Beclin1 pathway by binding PTEN to induce autophagy and exacerbate myocardial ischemia-reperfusion injury.

Patients with myocardial infarction have a much worse prognosis when they have myocardial ischemia-reperfusion (I/R) injury. Further research into the molecular basis of myocardial I/R injury is therefore urgently needed, as well as the identification of novel therapeutic targets and linkages to interventions. Three cysteine residues are present in DJ-1 at amino acids 46, 53, and 106 sites, with the cysteine at position 106 being the most oxidation-prone. This study sought to understand how oxidized DJ-1(C106) contributes to myocardial I/R damage. Rats' left anterior descending branches were tied off to establish a myocardial I/R model in vivo. A myocardial I/R model in vitro was established via anoxia/reoxygenation (A/R) of H9c2 cells. The results showed that autophagy increased after I/R, accompanied by the increased expression of oxidized DJ-1 (ox-DJ-1). In contrast, after pretreatment with NAC (N-acetylcysteine, a ROS scavenger) or Comp-23 (Compound-23, a specific antioxidant binding to the C106 site of DJ-1), the levels of ox-DJ-1, autophagy and LDH release decreased, and cell survival rate increased. Furthermore, the inhibition of interaction between ox-DJ-1 and PTEN could increase PTEN phosphatase activity, inhibit the p-IKK/NF-κB/Beclin1 pathway, reduce injurious autophagy, and alleviate A/R injury. However, BA (Betulinic acid, a NF-κB agonist) was able to reverse the protective effects produced by Comp-23 pretreatment. In conclusion, ox-DJ-1 could activate detrimental autophagy through the PTEN/p-IKK/NF-κB/Beclin1 pathway and exacerbate myocardial I/R injury.

Influence of germination on the bioactivity, structural, functional and volatile characteristics of different chickpea flours.

In this paper, the objective was to evaluated the impact of germination of chickpea cultivars (Muying1, Y2-514 and YZ-364) on the bioactivity, volatiles and functional properties. The results showed that the Vitamin C content of Muying1, Y2-514 and YZ-364 after germination significantly increased (p < 0.05). Moreover, the germination also caused a significant decrease in lower transition temperatures and enthalpy values in chickpea flours (p < 0.05). After germination treatment, ß-sheet and random coils in protein secondary structures increased and ß-turn decreased in YZ-364; α-helix, ß-sheet and random coil in Y2-514 and Muying1 decreased, while ß-turn increased. The germination significantly enhanced the functional properties of three chickpea flours (p < 0.05). It was proved that the germination significantly enhanced the total phenolic and flavonoids content, antioxidant activity and in vitro protein digestibility. The GC-IMS revealed that the germination could affect the contents of volatile compounds of chickpea flours.

Dosage-effect of selenium supplementation on blood glucose and oxidative stress in type 2 diabetes mellitus and normal mice.

BACKGROUND: The effectiveness of selenium (Se) supplementation on glycemic control is disparate. OBJECTIVE: This study aims to evaluate the effects of different dosages of Se diets on the blood glucose in type 2 diabetes mellitus (T2DM, db/db) and normal (db/m) mice. METHODS: The db/db and db/m mice were fed with different dosages of Se supplemented diets (0, 0.1, 0.3, 0.9, 2.7 mg/kg) for 12 weeks, respectively. Se concentrations of tissues, physical and biochemical characteristics, oxidative stress indexes and gene expression related to glucose, lipid metabolism and Se transporters of liver were detected. RESULTS: The Se concentrations in tissues were related to the dosages of Se supplementation in db/db (blood: slope=11.69, r = 0.924; skeletal muscle: slope=0.36, r = 0.505; liver: slope=22.12, r = 0.828; kidney: slope=11.81, r = 0.736) and db/m mice (blood: slope=19.89, r = 0.876; skeletal muscle: slope=2.80, r = 0.883; liver: slope=44.75, r = 0.717; kidney: slope=60.15, r = 0.960). Compared with Se2.7 group, the fasting blood glucose (FBG) levels of Se0.1 and Se0.3 group were decreased at week3 in db/db mice. Compared with control (Se0) group, the FBG levels of Se2.7 group were increased from week6 to week12 in db/m mice. The oral glucose tolerance test (OGTT) showed that the area under the curve (AUC) of Se0.3 group was lower than that of Se0.9 and Se2.7 group in db/m mice. Furthermore, compared with control group, the malondialdehyde (MDA) level in skeletal muscle of Se0.1 group was decreased, while that of Se2.7 group was increased in db/db mice; the glutathione peroxidase (GPx) activity in skeletal muscle of Se0.3, Se0.9 and Se2.7 group was increased both in db/db and db/m mice. For db/db mice, glucose-6-phosphatase catalytic (G6pc) expression of other groups were lower and fatty acid synthase (Fasn) expression of Se0.9 group were lower compared with Se0.3 group. For db/m mice, compared with Se0.3 group, (peroxisome proliferative activated receptor gamma coactivator 1 alpha) Pgc-1α expression of control and Se0.9 group were higher; (phosphoenolpyruvate carboxykinase 1) Pck1 expression of Se0.1, Se0.9, and Se2.7 group were higher. CONCLUSION: Low dosages (0.1 and 0.3 mg/kg) of Se supplementation exerted beneficial effects on FBG levels and glucose tolerance through regulating hepatic glycolysis and gluconeogenesis and inhibit the oxidative stress while high dosages of Se (0.9 and 2.7 mg/kg) supplementation enhanced FBG levels, impaired glucose tolerance and aggravate oxidative stress.

Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study.

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

Dietary Tomato Pectin Attenuates Hepatic Insulin Resistance and Inflammation in High-Fat-Diet Mice by Regulating the PI3K/AKT Pathway.

Chronic metabolic disease is a serious global health issue, which is accompanied by impaired insulin resistance. Tomato pectin (TP) is a naturally soluble complex hetero-polysaccharide with various biological functions. However, the impact of TP on hepatic insulin resistance in a high-fat diet (HFD) and its potential mechanism remains largely unknown. The results revealed that TP treatment significantly decreased the liver weight, hepatic fat accumulation and hepatic injury in HFD-fed mice. TP also improved fasting blood glucose levels and glucose tolerance in HFD-fed mice. The underlying mechanisms involved in the inflammation, oxidative stress and insulin signaling in the liver were also investigated by RT-qPCR and western blot, which indicated that TP ameliorated hepatic insulin resistance by regulating the PI3K/AKT/GSK-3ß pathway, increasing the expression of GLUT4, decreasing the expression of PECK and G6P as well as restoring antioxidant activities and suppressing the inflammation statues in HFD-fed mice. Our data showed that dietary TP has profound effects on hepatic insulin resistance, inflammation and oxidative stress, demonstrating that TP might be a promising therapeutic agent against insulin resistance and related chronic metabolic disease.

Plant-based proteins: advances in their sources, digestive profiles in vitro and potential health benefits.

Plant-based proteins (PBPs), which are environmentally friendly and sustainable sources of nutrition, can address the emerging challenges facing the global food supply due to the rapidly increasing population. PBPs have received much attention in recent decades as a result of high nutritional values, good functional properties, and potential health effects. This review aims to summarize the nutritional, functional and digestive profiles of PBPs, the health effects of their hydrolysates, as well as processing methods to improve the digestibility of PBPs. The diversity of plant protein sources plays an important role in improving the PBPs quality. Several types of models such as in vitro (the static and semi-dynamic INFOGEST) and in silico models have been proposed and used in simulating the digestion of PBPs. Processing methods including germination, fermentation, thermal and non-thermal treatment can be applied to improve the digestibility of PBPs. PBPs and their hydrolysates show potential health effects including antioxidant, anti-inflammatory, anti-diabetic, anti-hypertensive and anti-cancer activities. Based on the literature, diverse PBPs are ideal protein sources, and exhibit favorable digestive properties and health benefits that could be further improved by different processing technologies. Future research should explore the molecular mechanisms underlying the bioactivity of PBPs and their hydrolysates.

Role of automated functional imaging and myocardial work in assessment of cardiac function in children with obstructive sleep apnea.

BACKGROUND: Early identification of abnormal left ventricular function in children with obstructive sleep apnea (OSA) is difficult using conventional echocardiographic indices and commonly used clinical markers of myocardial damage. We sought to investigate the value of automatic function imaging and myocardial work parameters in predicting early cardiac impairment in children having OSA with preserved left heart function and thereby identifying an optimal index for assessment. PATIENTS AND METHODS: Fifty-two children who presented with symptoms of nocturnal sleep snoring and open-mouth breathing and 34 healthy controls were enrolled in this study. Clinical characteristics and conventional echocardiographic data were collected, and image analysis was performed using two-dimensional speckle-tracking echocardiography to obtain left ventricular global longitudinal strain (GLS), post-systolic index, peak strain dispersion, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. RESULTS: Children with OSA had significantly lower GLS, GWI, and GCW than those without (P < 0.05). Additionally, GWI (ß = -32.87, 95% CI: -53.47 to -12.27), and GCW (ß = -35.09, 95% CI: -55.35 to -14.84) were found to correlate with the disease severity in the multiple linear regression mode, with worsening values observed as the severity of the disease increased. ROC curve analysis revealed that GCW was the best predictor of myocardial dysfunction, with an AUC of 0.809 (P < 0.001), and the best cutoff point for diagnosing myocardial damage in children with OSA was 1965.5 mmHg%, with a sensitivity of 92.5% and a specificity of 58.7%. CONCLUSIONS: GLS, GWI, and GCW were identified as predictors of myocardial dysfunction in children with OSA, with GCW being the best predictor.

27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway.

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.

Intensified conditioning regimens with total marrow irradiation/etoposide/cyclophosphamide and busulfan/etoposide/cyclophosphamide overcome the impact of pre-transplant minimal residual disease on outcomes in high-risk acute lymphoblastic leukemia patients in complete remission.

PURPOSE: Among high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), those with positive minimal residual disease (MRD) are susceptible to poor outcomes. Therefore, it is necessary to determine the most suitable preparatory regimen for these patients. METHODS: Data were analyzed from 141 patients who received allo-HSCT and were diagnosed with high-risk ALL. These patients underwent intensified conditioning regimens, including either total marrow and lymphoid irradiation (TMLI)-etoposide (VP16)-cyclophosphamide (CY) or busulfan (BU)-VP16-CY between October 2016 and November 2022. A total of 141 individuals were in complete remission (CR) before transplantation and, among all patients, 90 individuals exhibited a negative MRD status and 51 patients had a positive MRD status. RESULTS: In patients who tested negative for MRD, the incidence of relapse within a 2-year timeframe was 25.0% (24.8%-25.5%), compared with 32.2% (31.2%-33.2%) in MRD-positive patients; however, this difference was not statistically significant. There were no significant differences in the 2-year disease-free survival (DFS) and 2-year overall survival (OS) rates between the MRD-negative and MRD-positive groups (DFS: 67.2% (57.9%-78.1%) vs. 55.5% (42.6%-72.3%); OS: 69.0% (61.9%-88.2%) vs. 66.7% (53.9%-82.5%)). Furthermore, no notable variations were observed in the occurrence of transplant-related mortality (TRM) and graft-versus-host disease (GVHD) across the two groups. CONCLUSION: This study reveals the benefits of TMLI-VP16-CY and BU-VP16-CY conditioning regimens in high-risk ALL patients with CR and MRD-positive status. A large-scale prospective clinical trial is warranted in the future.

Structural and functional characterization of exopolysaccharide from Leuconostoc citreum BH10 discovered in birch sap.

In this study, Leuconostoc citreum BH10, an endophytic strain, was isolated from aseptically collected xylem sap of birch for the first time, and its exopolysaccharide (LCEPS) production was up to 46.31 g/L in glucan producing medium. The produced LCEPS was purified to obtain two water-soluble fractions, named as LCEPS-1 and LCEPS-2, respectively. The major fraction LCEPS-1 was characterized to be comprised of glucose with average molecular weight of 6.34 × 106 Da. The structure of LCEPS-1 was investigated by spectroscopy analysis, which revealed that LCEPS-1 was identified with containing 90.45 % α-(1,6) linkages in the main chains and 9.55 % α-(1,3) branch linkages. The scanning electron microscope results demonstrated that the dried LCEPS-1 appeared porous surface overlaid with an irregular glittering. The water solubility index (WSI) and water holding capacity (WHC) of LCEPS-1 were 88.02 ± 1.69 % and 241.43 ± 6.38 %, respectively. Besides, it exhibited high thermal stability as well as fine antioxidant activities. Taken together, the results indicated that LCEPS-1 could have good potentiality to be applied in fields of foods, cosmetics, nutraceuticals and pharmaceutical industries as the natural agent.

Effectiveness of in vivo T-cell-depleted regimen containing porcine anti-lymphocyte globulin or rabbit anti-thymocyte globulin in preventing acute graft-versus-host disease after haploidentical haematopoietic stem cell transplantation.

To compare the clinical efficacy of porcine anti-lymphocyte globulin (p-ALG) and rabbit anti-thymocyte globulin (r-ATG) in the treatment of haematological malignancies using haploidentical haematopoietic stem cell transplantation (haplo-HSCT), this study was conducted. The incidences of neutrophil and platelet engraftment, respectively, were 100%, 93.6% and 94.4%; 100%, 93.6% and 90.3% in p-ALG 75 mg/kg (n = 57), p-ALG 90 mg/kg (n = 49), and r-ATG 7.5 mg/kg (n = 72). The median time to neutrophil engraftment and platelet engraftment were 11, 12 and 12 days (p = 0.032); 13, 14 and 13 days (p = 0.013), respectively. The incidence of grades II-IV acute graft-versus-host disease and cumulative incidence of chronic graft-versus-host disease were 16.7% versus 12.5% versus 13.3% (p = 0.817) and 14.7% versus 12.1% versus 19.5% in p-ALG 75 mg/kg, p-ALG 90 mg/kg and r-ATG groups. Notably, the cytomegalovirus infection rate in the p-ALG 75 mg/kg group was significantly lower than the other two groups. The cumulative incidence of 2-year relapse and 2-year overall survival rates were similar (p = 0.901, p = 0.497). The lower dose of p-ALG (75 mg/kg) had a similar efficacy and safety profile compared with r-ATG (7.5 mg/kg) in the setting of haplo-HSCT. Therefore, p-ALG (75 mg/kg) may be an appropriate alternative to r-ATG in the conditioning regimen of haplo-HSCT.

Tissue ultrasound imaging based on wavelet correlation analysis and pulse-inversion technique.

BACKGROUND: Pulse-inversion-based tissue harmonic imaging has been utilized for many years because it can effectively eliminate the harmonic leakage and produce low side-lobe. However, the pulse inversion method is sensitive to imaging object movements, which may result in motion artifacts. Spatial resolution and contrast were limited. OBJECTIVE: To improve ultrasound image quality by a new pulse-inversion-based tissue harmonic imaging technique. METHODS: Continuous wavelet transform is applied to investigate the correlation between mother wavelet and the received echoes from two opposite pulses. To get a better correlation, a novel mother wavelet named 'tissue wavelet' is designed based on the Khokhlov-Zabolotskaya- Kuznetsov (KZK) wave equation. Radio frequency data were obtained from open Ultrasonix SonixTouch imaging system. Experiments were carried on ultrasonic tissue phantom, human carotid artery and human liver. RESULTS: The average improvement of lateral spatial resolution is 49.52% compared to pulse-inversion-based tissue second-harmonic Imaging (PIHI). Contrast ratio (CR) and contrast-to-noise ratio (CNR) increased by 5.55 dB and 1.40 dB over PIHI. Tissue wavelet performs better than Mexh and Morl wavelet in lateral spatial resolution, CR, and CNR. CONCLUSION: The proposed technique effectively improves the imaging quality in lateral spatial resolution, CR, and CNR.