Protective effects of butyric acid during heat stress on the survival, immune response, histopathology, and gene expression in the hepatopancreas of juvenile pacific shrimp (L. Vannamei).

This study looked at the effects of adding butyric acid (BA) to the diets of juvenile Pacific shrimp and how it affected their response to survival, immunity, histopathological, and gene expression profiles under heat stress. The shrimp were divided into groups: a control group with no BA supplementation and groups with BA inclusion levels of 0.5 %, 1 %, 1.5 %, 2 %, and 2.5 %. Following the 8-week feeding trial period, the shrimp endured a heat stress test lasting 1 h at a temperature of 38 °C. The results showed that the control group had a lower survival rate than those given BA. Interestingly, no mortality was observed in the group receiving 1.5 % BA supplementation. Heat stress had a negative impact on the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the control group. Still, these activities were increased in shrimp fed the BA diet. Similar variations were observed in AST and ALT fluctuations among the different groups. The levels of triglycerides (TG) and cholesterol (CHO) increased with high temperatures but were reduced in shrimp-supplemented BA. The activity of an antioxidant enzyme superoxide dismutase (SOD) increased with higher BA levels (P < 0.05). Moreover, the groups supplemented with 1.5 % BA exhibited a significant reduction in malondialdehyde (MDA) content (P < 0.05), suggesting the potential antioxidant properties of BA. The histology of the shrimp's hepatopancreas showed improvements in the groups given BA. Conversely, the BA significantly down-regulated the HSPs and up-regulated MnSOD transcript level in response to heat stress. The measured parameters determine the essential dietary requirement of BA for shrimp. Based on the results, the optimal level of BA for survival, antioxidant function, and immunity for shrimp under heat stress is 1.5 %.

4-Octyl itaconate attenuates glycemic deterioration by regulating macrophage polarization in mouse models of type 1 diabetes.

BACKGROUND: Pancreatic beta cell dysfunction and activated macrophage infiltration are early features in type 1 diabetes pathogenesis. A tricarboxylic acid cycle metabolite that can strongly activate NF-E2-related factor 2 (Nrf2) in macrophages, itaconate is important in a series of inflammatory-associated diseases via anti-inflammatory and antioxidant properties. However, its role in type 1 diabetes is unclear. We used 4-octyl itaconate (OI), the cell-permeable itaconate derivate, to explore its preventative and therapeutic effects in mouse models of type 1 diabetes and the potential mechanism of macrophage phenotype reprogramming. METHODS: The mouse models of streptozotocin (STZ)-induced type 1 diabetes and spontaneous autoimmune diabetes were used to evaluate the preventative and therapeutic effects of OI, which were performed by measuring blood glucose, insulin level, pro- and anti-inflammatory cytokine secretion, histopathology examination, flow cytometry, and islet proteomics. The protective effect and mechanism of OI were examined via peritoneal macrophages isolated from STZ-induced diabetic mice and co-cultured MIN6 cells with OI-pre-treated inflammatory macrophages in vitro. Moreover, the inflammatory status of peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients was evaluated after OI treatment. RESULTS: OI ameliorated glycemic deterioration, increased systemic insulin level, and improved glucose metabolism in STZ-induced diabetic mice and non-obese diabetic (NOD) mice. OI intervention significantly restored the islet insulitis and beta cell function. OI did not alter the macrophage count but significantly downregulated the proportion of M1 macrophages. Additionally, OI significantly inhibited MAPK activation in macrophages to attenuate the macrophage inflammatory response, eventually improving beta cell dysfunction in vitro. Furthermore, we detected higher IL-1ß production upon lipopolysaccharide stimulation in the PBMCs from type 1 diabetes patients, which was attenuated by OI treatment. CONCLUSIONS: These results provided the first evidence to date that OI can prevent the progression of glycemic deterioration, excessive inflammation, and beta cell dysfunction predominantly mediated by restricting macrophage M1 polarization in mouse models of type 1 diabetes.

Different Types of Family History of Stroke and Stroke Risk: Results Based on 655,552 Individuals.

BACKGROUND: Many studies concentrated on the relationships between different types of family history and stroke, but they have not arrived at an unified conclusion. We conducted a comprehensive systematic review to further evaluate the associations. METHODS: Different databases were searched for related studies published from 1990 to August 2017. The relative risk was considered as the common measure of association across different studies. Heterogeneity of effects across studies was quantified by I2. RESULTS: Sixteen published studies (total participants: 655,552) were eligible in this study. The pooled multifactorial adjusted relative risk (RR) (95% confidence interval [CI]) was 1.40 (1.18, 1.67) for individuals with paternal history, 1.36 (1.20, 1.53) for those with maternal history, and 1.44 (1.17, 1.77) for those with sibling history. Based on cohort studies, the pooled adjusted RRs (95%CIs) for paternal, maternal, and sibling history were 1.33 (1.11-1.59), 1.28 (1.14-1.45), and 1.24 (1.01-1.51), respectively, all of which were smaller than those based on case-control and cross-sectional studies. In studies with large sample size, the respective adjusted RR (95%CI) of stroke for paternal, maternal, and sibling history was 1.30 (1.09, 1.56), 1.30 (1.18, 1.44), and 1.26 (1.02, 1.56), which was lower than that in studies with small sample size. CONCLUSIONS: Each type of family history of stroke was associated with an increased stroke risk. We could not find significant differences among stroke risks relating to different types of family history of stroke. Thus, paternal, maternal, and sibling history require our equal attention in the stroke prevention and control work.

Autophagy protects against cholesterol-induced apoptosis in pancreatic ß-cells.

Autophagy is believed to play an important role in maintaining homeostasis in pancreatic ß-cells during insulin resistance. This study investigated the role of autophagy in ß-cell damage induced by cholesterol and its possible activation mechanism. Rat and mouse pancreatic ß-cell lines INS-1 and ßTC-6 were incubated with cholesterol alone or in combination with autophagy inhibitors E-64d/Pepstatin A or bafilomycin A1. DAPI staining, western blotting, transmission electron microscopy and immunofluorescence were conducted to assess the effects of autophagy inhibitors on cholesterol-induced apoptosis and autophagy activity. An increase in FITC-LC3 fluorescence dots, autophagic vacuoles and LC3-II protein indicated that autophagy was activated in cells treated with cholesterol. This was further confirmed by blocking the natural turnover processes in lysosomes and autolysosomes with autophagy inhibitors, suggesting enhanced autophagic activity rather than blockage of autophagy. Furthermore, inhibition of autophagy significantly augmented the activation of caspase 3 and the percentage of cholesterol-induced apoptotic nuclei. These results demonstrate that autophagy plays a protective role against cholesterol-induced apoptosis in pancreatic ß-cells.

miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer.

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3'UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC.

[Clinical features of mild encephalitis/encephalopathy with a reversible splenial lesion in children].

OBJECTIVE: To investigate the clinical features of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in children. METHODS: The clinical data of 8 children with MERS were retrospectively analyzed. RESULTS: The mean age of onset was 5 years and 2 months (range 10 months to 12 years). The major clinical features included a history of prodromal infection, and among these children, 5 had pyrexia and 4 had vomiting. Of all the children, 6 were manifested as convulsion and 3 each were manifested as disturbance of consciousness and paroxysmal paropsia. Cranial diffusion-weighted magnetic resonance imaging (MRI) showed high signals in the splenium of the corpus callosum. Among these children, one child had symmetric and multiple long T1 and long T2 signals in the bilateral centrum semiovale and part of the temporal white matter. MRI reexamination performed after 5-30 days showed the disappearance of abnormal signals in all the children. The children were followed up for 3 months to 2 years, and no child experienced abnormal neurodevelopment. CONCLUSIONS: The development of MERS in children is closely associated with infection. MERS is characterized by high signals in the splenium of the corpus callosum on cranial diffusion-weighted MRI. Most children have good prognosis.

Peroxydisulfate-based Non-radical Oxidation of Rhodamine B by Fe-Mn Doped Granular Activated Carbon: Kinetics and Mechanism Study.

While numerous persulfate-based advanced oxidation processes (AOPs) have been studied based on fancy catalysts, the practical combination of Fe or Mn modified granular activated carbon (GAC) has seldom been investigated. The present study focused on a green and readily synthesized Fe-Mn bimetallic oxide doped GAC (Fe-Mn@GAC), to uncover its catalytic kinetics and mechanism when used in the peroxydisulfate (PDS)-based oxidation process for degrading Rhodamine B (RhB), a representative xenobiotic dye. The synthesized Fe-Mn@GAC was characterized by SEM-EDS, XRD, ICP-OES and XPS analyses to confirm its physicochemical properties. The catalytic kinetics of Fe-Mn@GAC+PDS system were evaluated under varying conditions, including PDS and catalyst dosages, solution pH, and the presence of anions. It was found Fe-Mn@GAC exhibited robust catalytic performance, being insensitive to a wide pH range from 3 to 11, and the presence of anions such as Cl-, SO4 2-, NO3 - and CO3 2-. The catalytic mechanism was investigated by EPR and quenching experiments. The results indicated the catalytic system processed a non-radical oxidation pathway, dominated by direct electron transfer between RhB and Fe-Mn@GAC, with singlet oxygen (1O2) playing a secondary role. The catalytic system also managed to maintain a RhB removal above 81 % in successive 10 cycles, and recover to 89.5 % after simple DI water rinse, showing great reusability. The catalytic system was further challenged by real dye-containing wastewater, achieving a decolorization rate of 84.5 %. This work not only provides fresh insight into the kinetics and mechanism of the Fe-Mn@GAC+PDS catalytic system, but also demonstrates its potential in the practical application in real dye-containing wastewater treatment.

Body image, self-efficacy, and sleep quality among patients with breast cancer: A latent profile and mediation analysis.

PURPOSE: As a sign of femininity, impaired breast after surgery causes particularly confusion for patients with breast cancer resulting in increased body image distress, which has negative impacts on sleep quality. And self-efficacy enables patients to use positive and effective coping strategies to maintain a favorable night's sleep. Therefore, our study is to explore the heterogeneity in body image experienced by patients with breast cancer and to examine the mediation effects of self-efficacy between body image and sleep quality. METHOD: Between July 2023 and October 2023, 251 patients with breast cancer were recruited for the Be Resilient to Breast Cancer program. They responded to the General Perceived Self-Efficacy Scale, Body Image Scale, and Pittsburgh Sleep Quality Index Scale. Data were analyzed using a latent profile analysis (LPA) and mediation analysis. RESULTS: Results of the LPA indicated that body image could be classified into three subgroups as follows: low (43.0%), moderate (45.5%), and high (11.5%). Furthermore, the mediation analysis demonstrated two partially mediated effects upon comparing the low and moderate (standard error, SE = 0.548, 95% confidence interval, CI = 0.009, 0.366) and the high and low (SE = 0.848, 95% CI = 0.570, 3.909) body image groups. CONCLUSION: Heterogeneity exists in body image, and self-efficacy mediates the relationship between body image and sleep quality. Hence, promoting self-efficacy can buffer the negative impacts of body image on sleep quality in patients with breast cancer, and self-efficacy-orientated interventions should also receive more attention in clinic.

The interplay between stigma and sleep quality in breast cancer: A cross-sectional network analysis.

PURPOSE: Stigma, a subjective internal shame, arises from the association of cancer with death. Sleep quality can be considered a product of stigma. However, the extent of overlap or difference between the two remains unclear. METHODS: In total, 512 survivors with breast cancer were recruited from the "Be Resilient to Breast Cancer" project between May and August 2023. This study estimated the stigma, sleep quality, and their relationship by conducting a cross-sectional network analysis. The social impact scale and Pittsburgh Sleep Quality Index scale were employed in this study. RESULTS: The core symptom for stigma from the network analysis was alienation by people (Strength = 1.213, Betweenness = 13, Closeness = 0.00211). The core symptom for sleep quality were the sleep quality (Str = 1.114, Bet = 17, Clo = 0.01586). Regarding the combination network, results showed that self-isolation and daytime dysfunction were the bridge nodes and that daytime dysfunction was positively associated with feeling less capable than before (according to self) (r = 0.15). CONCLUSION: Our study demonstrates the core symptoms in different symptomatic networks, which can be targeted for treatment personalization and aid in the improvement of sleep quality and stigma in breast cancer patients.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Moral Judgments of Human vs. AI Agents in Moral Dilemmas.

Artificial intelligence has quickly integrated into human society and its moral decision-making has also begun to slowly seep into our lives. The significance of moral judgment research on artificial intelligence behavior is becoming increasingly prominent. The present research aims at examining how people make moral judgments about the behavior of artificial intelligence agents in a trolley dilemma where people are usually driven by controlled cognitive processes, and in a footbridge dilemma where people are usually driven by automatic emotional responses. Through three experiments (n = 626), we found that in the trolley dilemma (Experiment 1), the agent type rather than the actual action influenced people's moral judgments. Specifically, participants rated AI agents' behavior as more immoral and deserving of more blame than humans' behavior. Conversely, in the footbridge dilemma (Experiment 2), the actual action rather than the agent type influenced people's moral judgments. Specifically, participants rated action (a utilitarian act) as less moral and permissible and more morally wrong and blameworthy than inaction (a deontological act). A mixed-design experiment provided a pattern of results consistent with Experiment 1 and Experiment 2 (Experiment 3). This suggests that in different types of moral dilemmas, people adapt different modes of moral judgment to artificial intelligence, this may be explained by that when people make moral judgments in different types of moral dilemmas, they are engaging different processing systems.

Deficiency of lipopolysaccharide binding protein facilitates adipose browning, glucose uptake and oxygen consumption in mouse embryonic fibroblasts via activating PI3K/Akt/mTOR pathway and inhibiting autophagy.

This study aimed to explore the role of lipopolysaccharide-binding protein (LBP) in adipose browning. Mouse embryonic fibroblasts (MEFs) were treated with differentiation induction reagents and Perifosine (Akt inhibitor), with the transfection of Atg5, short hairpin RNA targeting LBP (shLBP), and Atg5 (shAtg5). The expression levels of LBP, inflammatory markers , brown fat markers, lipid metabolism marker, autophagy markers, insulin signaling-related molecules , p-mTOR, mTOR, p-Akt, Akt, p-PI3K, and PI3K were quantified or determined by Western blot, qRT-PCR, and immunofluorescence assay. The formation of lipid was examined through Oil red O staining assay. The consumption of oxygen was assessed using a Seahorse XF96 analyzer, and the uptake of glucose was evaluated by [3H]-2-deoxy-D-glucose uptake assay. Deficiency of LBP promoted adipose browning, oxygen consumption, glucose uptake, and insulin sensitivity in differentiated MEFs, where it inhibited inflammation and autophagy. All of the effects above were reversed by Atg5 overexpression. Meanwhile, the knockdown of Atg5 strengthened the activation of PI3K/Akt/mTOR pathway induced by the depletion of LBP, while Perifosine partly reversed the activation of differentiated MEFs. The knockdown of LBP facilitated adipose browning, glucose uptake, and oxygen consumption in MEFs via the activation of PI3K/Akt/mTOR pathway and the inhibition of autophagy.

Dual Contrastive Learning Network for Graph Clustering.

Graph representation is an important part of graph clustering. Recently, contrastive learning, which maximizes the mutual information between augmented graph views that share the same semantics, has become a popular and powerful paradigm for graph representation. However, in the process of patch contrasting, existing literature tends to learn all features into similar variables, i.e., representation collapse, leading to less discriminative graph representations. To tackle this problem, we propose a novel self-supervised learning method called dual contrastive learning network (DCLN), which aims to reduce the redundant information of learned latent variables in a dual manner. Specifically, the dual curriculum contrastive module (DCCM) is proposed, which approximates the node similarity matrix and feature similarity matrix to a high-order adjacency matrix and an identity matrix, respectively. By doing this, the informative information in high-order neighbors could be well collected and preserved while the irrelevant redundant features among representations could be eliminated, hence improving the discriminative capacity of the graph representation. Moreover, to alleviate the problem of sample imbalance during the contrastive process, we design a curriculum learning strategy, which enables the network to simultaneously learn reliable information from two levels. Extensive experiments on six benchmark datasets have demonstrated the effectiveness and superiority of the proposed algorithm compared with state-of-the-art methods.

Association between stigma and sleep quality in patients with breast cancer: A latent profile and mediation analysis.

PURPOSE: This study aims to identify the heterogeneity in the stigma experienced by patients with breast cancer and examine the mediation effect of resilience on the relation between stigma and sleep quality. METHOD: A total of 396 patients with breast cancer were enrolled from Be Resilient to Breast Cancer (BRBC) program between January and April 2023. Participants completed the Social Impact Scale, the 10-item Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index Scale. Latent profile analysis (LPA) and mediation analysis were conducted to analyze the data. RESULTS: LPA categorized stigma into three subgroups, namely low-stigma (21.9%), moderate-stigma (64.9%), and high-stigma (13.2%). Mediation analysis revealed a fully mediated effect in the comparison between low-stigma and moderate-stigma groups (standard error [SE] = 0.13, 95%CI = 0.06,0.56), whereas a partially mediated effect was observed in the comparison between low-stigma and high-stigma groups (SE = 0.18, 95%CI = 0.39,1.10). CONCLUSIONS: Stigma is a significant factor to sleep quality in breast cancer and resilience could act as a robust buffer against stigma resulting in improved sleep quality. Resilience-based interventions might be helpful in this population.

Effects of Plant-Derived Glycerol Monolaurate (GML) Additive on the Antioxidant Capacity, Anti-Inflammatory Ability, Muscle Nutritional Value, and Intestinal Flora of Hybrid Grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂).

In a context where the search for plant-derived additives is a hot topic, glycerol monolaurate (GML) was chosen as our subject to study its effect on grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). Seven gradient levels of GML (0, 600, 1200, 1800, 2400, 3000, and 3600 mg/kg) were used for the experiment. Based on our experiments, 1800 mg/kg GML significantly increased the final body weight (FBW) and weight gain rate (WGR). GML increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased malondialdehyde (MDA). Adding 1800 mg/kg GML also significantly increased the levels of lauric acid (C12:0) (LA), n-3 polyunsaturated fatty acids (PFA), and the n-6 PFA-to-n-3/n-6 ratio, while significantly decreasing the levels of saturated fatty acids (SFA). Dietary supplementation with GML significantly inhibited the expression of pro-inflammatory factors and reduced the occurrence of inflammation. GML improved intestinal flora and the abundance of beneficial bacteria (Bacillus, Psychrobacter, Acinetobacter, Acinetobacter, Stenotrophomonas, and Glutamicibacter). It provides a theoretical basis for the application of GML in aquafeed and greatly enhances the possibility of using GML in aquafeed. Based on the above experimental results, the optimum level of GML in grouper feed is 1800 mg/kg.

Novel intertidal wetland sediment-inoculated moving bed biofilm reactor treating high-salinity wastewater: Metagenomic sequencing revealing key functional microorganisms.

In this study, two lab-scale moving bed biofilm reactors (MBBR), seeded with intertidal wetland sediment (IWS) and activated sludge (AS), were constructed to compare their performances in treating high-salinity (3%) wastewater. Under a wide range of influent TOC (178-620 mg/L) and NH4+-N (25-100 mg/L), both the MBBRs (Riws and Ras) exhibited excellent TOC removal efficiencies of >95%. Regarding nitrogen reduction, Riws exhibited a significantly superior TN removal efficiency of 90.2 ± 1.8% than that of Ras (76.8 ± 2.9%). A correlation analysis was innovatively conducted comparing the results between metagenomic sequencing and DNA pyrosequencing, and positive linear relationships were found with R2 values of 0.763-0.945. Meanwhile, for illustration of different TN removal performance, nitrogen metabolic pathways were also assessed. Moreover, a list of functional oxidases (EC: 1.13.11.1, EC: 1.13.11.2, EC: 1.13.11.24, EC: 1.13.12.16, EC: 1.4.3.4, EC: 1.16.3.3, EC: 1.14.14.28) was found in IWS, revealing its potential in degradation of recalcitrant organics.

Hemodynamics derived from computational fluid dynamics based on magnetic resonance angiography is associated with functional outcomes in atherosclerotic middle cerebral artery stenosis.

BACKGROUND: To investigate the relationship between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH), hemodynamics, and functional outcome in atherosclerotic middle cerebral artery (MCA) stenosis using a computational fluid dynamics (CFD) model based on magnetic resonance angiography (MRA), according to a modified Rankin Scale (mRS) at 3 months. METHODS: A total of 120 patients with 50-99% atherosclerotic MCA stenosis were included. The training and internal validation groups were composed of 99 participants and 21 participants, respectively. Demographic, imaging data, and functional outcome (mRS at 3 months) were collected. Hemodynamic parameters were obtained from the CFD model. The FVH score was based on the number of territories where FVH is positive, according to the spatial distribution in the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). The prediction models were constructed according to clinical and hemodynamic parameters using multivariate logistic analysis. The DeLong test compared areas under the curves (AUCs) of the models. RESULTS: The multivariable logistic regression analysis showed that the National Institute of Health Stroke Scale (NIHSS) at admission, hypertension, hyperlipidemia, the ratio of wall shear stress before treatment (WSSRbefore), and difference in the ratio of wall shear stress (WSSR) were independently associated with functional outcome (all P<0.05). In the training group before treatment, the AUC of model 1a (only clinical variables) and 2a (clinical variables with addition of WSSRbefore) were 0.750 and 0.802. After treatment, the AUC of model 1b (only clinical variables) and 2b (clinical variables with addition of difference in WSSR) were 0.815 and 0.883, respectively. The AUC of models with hemodynamic parameters was significantly higher than the models based on clinical variables only (all P<0.05, DeLong test). In the internal validation group before treatment, the AUC of the model (clinical variables) was 0.782, and that of the model (clinical variables and WSSRbefore) was 0.800. After treatment, the AUC of the model (clinical variables) was 0.833, and that of the model (clinical variables and difference in WSSR) was 0.861. There were no significant differences between the good and the poor functional outcome group concerning FVHbefore scores before treatment (0.30±0.81 vs. 0.26±0.97; P=0.321) and FVHafter scores after treatment (0.08±0.39 vs. 0.00±0.00; P=0.244). CONCLUSIONS: Hemodynamics was associated with functional outcomes in patients with ischemic stroke attributed to atherosclerotic MCA stenosis, while FVH was not. Hemodynamic parameters were of great importance in the prediction models.

Correlation of Vitek 2 and Agar dilution for levofloxacin susceptibility testing and clinical outcomes of Enterobacterales bacteremia with 2019 CLSI breakpoints.

In 2019, the CLSI lowered the susceptible levofloxacin breakpoints for Enterobacterales from a MIC of ≤2 µg/mL to ≤0.5 µg/mL. The study evaluated the correlation between the susceptibility profiles obtained by the Vitek 2 and agar dilution (AD) methods in levofloxacin MIC ≤2 µg/mL isolates and its clinical impacts. Two hundred fifty-three Enterobacterales isolates and 222 patients treated with levofloxacin for Enterobacterales bacteremia were enrolled for analysis. There was 86.2% categorical agreement, 5 very major errors, and 30 minor errors based on the 2019 CLSI breakpoints. Higher levofloxacin MICs (1 or 2 µg/mL) determined using Vitek 2 or AD predicted early clinical failure (P < 0.001 for Vitek 2 and P = 0.001 for AD). In conclusion, Vitek 2 performance for levofloxacin susceptibility testing of Enterobacterales declined according to the 2019 CLSI criteria compared with the pre-2019 criteria. Although discrepant results were obtained, the MICs measured by Vitek 2 could still predict treatment outcomes.

A Prediction Model for Prediabetes Risk in Middle-Aged and Elderly Populations: A Prospective Cohort Study in China.

BACKGROUND: To investigate indicators for prediabetes risk and construct a prediction model for prediabetes incidences in China. METHODS: In this study, 551 adults aged 40-70 years had normal glucose tolerance (NGT) and normal hemoglobin A1c (HbA1c) levels at baseline. Baseline data including demographic information, anthropometric measurements, and metabolic profile measurements were collected. The associations between possible indicators and prediabetes were assessed by the Cox proportional-hazards model. The predictive values were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: During an average of 3.35 years of follow-up, the incidence of prediabetes was found to be 19.96% (n = 110). In the univariate analyses, fasting plasma glucose (FPG), fasting serum insulin (FINS), 2 h plasma glucose (2hPG), HbA1c, serum uric acid (SUA), waist circumference (WC), smoking, and family history of diabetes (FHD) were found to be significantly correlated with prediabetes. In the multivariable analyses, WC (hazard ratio (HR): 1.032; 95% confidence interval (CI): 1.010, 1.053; p = 0.003), FHD (HR: 1.824; 95% CI: 1.250, 2.661; p = 0.002), HbA1c (HR: 1.825; 95% CI: 1.227, 2.714; p = 0.003), and FPG (HR: 2.284; 95% CI: 1.556, 3.352; p < 0.001) were found to be independent risk factors for prediabetes. A model that encompassed WC, FHD, HbA1c, and FPG for predicting prediabetes exhibited the largest discriminative ability (AUC: 0.702). CONCLUSIONS: WC, FHD, HbA1c, and FPG are independently correlated with the risk of prediabetes. Furthermore, the combination of these predictors enhances the predictive accuracy of prediabetes.

Exploring the molecular targets and mechanisms of [10]-Gingerol for treating triple-negative breast cancer using bioinformatics approaches, molecular docking, and in vivo experiments.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive among breast cancer subtypes with the worst prognosis. Ginger is widely used in pharmaceuticals and as food. Its anticancer properties are known, but the mechanism is still unclear. [10]-Gingerol is one of the main phenolic compounds isolated from ginger. Studying the biological effects of [10]-Gingerol is of great significance to understand the efficacy of ginger. METHODS: In this study, the therapeutic effects of [10]-Gingerol on TNBC cells were studied using network pharmacology, molecular docking, and in vitro experiments, and the target and mechanism of action were explained. RESULTS: A total of 48 targets of ginger for the treatment of TNBC were found. These targets might interfere with the growth of TNBC by participating in many pathways, such as endocrine resistance, progesterone-mediated oocyte maturation, estrogen signaling pathway, and cellular senescence. Prognostic analyses indicated that the JUN, FASN, ADRB2, ADRA2A, and PGR were the hub genes, while molecular docking predicted the stable binding of ADRB2 protein with drug compounds. Additionally, [10]-Gingerol could induce apoptosis by regulating the caspase activation. CONCLUSIONS: [10]-Gingerol affects the growth of TNBC through multiple action targets and participating in multiple action pathways. ADRB2 and apoptosis pathways might be important target pathways for [10]-Gingerol in the treatment of TNBC.