Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage - Fig 3

<p><b>(A</b>) Occludin immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, #p<0.01, *p<0.05 vs. SAH+vehicle group at day 3. <b>(B)</b> ZO-1 immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, #p<0.01 vs. SAH+vehicle group at day 3. <b>(C)</b> Claudin-5 immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, *p<0.05 vs. SAH+vehicle group at day 3.</p

Ferritin immunoreactivity, and the ferritin heavy chain (FTH) and light chain (FTL) protein levels in cortex at day 3 after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle, scale bar = 20μm.

<p>Values are mean ± SD; n = 3 for each group, #p<0.01 vs. SAH+vehicle group at day 3.</p

Behavior and activity scores.

<p>Behavior and activity scores.</p

Data_Sheet_2_Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella.docx

The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections.</p

DataSheet1_Dapagliflozin promotes angiogenesis in hindlimb ischemia mice by inducing M2 macrophage polarization.docx

Critical limb ischemia (CLI) is associated with a higher risk of limb amputation and cardiovascular death. Dapagliflozin has shown great potential in the treatment of cardiovascular disease. However, the effects of dapagliflozin on CLI and the underlying mechanisms have not been fully elucidated. We evaluated the effect of dapagliflozin on recovery from limb ischemia using a mouse model of hindlimb ischemia. The flow of perfusion was evaluated using a laser Doppler system. Tissue response was assessed by analyzing capillary density, arterial density, and the degree of fibrosis in the gastrocnemius muscle. Immunofluorescence and Western blot were used to detect the expression of macrophage polarization markers and inflammatory factors. Our findings demonstrate the significant impact of dapagliflozin on the acceleration of blood flow recovery in a hindlimb ischemia mouse model, concomitant with a notable reduction in limb necrosis. Histological analysis revealed that dapagliflozin administration augmented the expression of key angiogenic markers, specifically CD31 and α-SMA, while concurrently mitigating muscle fibrosis. Furthermore, our investigation unveiled dapagliflozin’s ability to induce a phenotypic shift of macrophages from M1 to M2, thereby diminishing the expression of inflammatory factors, including IL-1β, IL-6, and TNF-α. These effects were partially mediated through modulation of the NF-κB signaling pathway. Lastly, we observed that endothelial cell proliferation, migration, and tube-forming function are enhanced in vitro by utilizing a macrophage-conditioned medium derived from dapagliflozin treatment. Taken together, our study provides evidence that dapagliflozin holds potential as an efficacious therapeutic intervention in managing CLI by stimulating angiogenesis, thereby offering a novel option for clinical CLI treatment.</p

Data_Sheet_1_Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella.XLSX

The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections.</p

Image_1_A novel predictive model for new-onset atrial fibrillation in patients after isolated cardiac valve surgery.TIF

BackgroundPostoperative atrial fibrillation (POAF) is a severe complication after cardiac surgery and is associated with an increased risk of ischemic stroke and mortality. The main aim of this study was to identify the independent predictors associated with POAF after isolated valve operation and to develop a risk prediction model.MethodsThis retrospective observational study involved patients without previous AF who underwent isolated valve surgery from November 2018 to October 2021. Patients were stratified into two groups according to the development of new-onset POAF. Baseline characteristics and perioperative data were collected from the two groups of patients. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for the occurrence of POAF, and the results of the multivariate analysis were used to create a predictive nomogram.ResultsA total of 422 patients were included in the study, of which 163 (38.6%) developed POAF. The Multivariate logistic regression analysis indicated that cardiac function (odds ratio [OR] = 2.881, 95% confidence interval [CI] = 1.595–5.206; P ConclusionCardiac function, left atrial diameter index, operative time, neutrophil count, and fever were independent predictors of POAF in patients with isolated valve surgery. Establishing a nomogram model based on the above predictors helps predict the risk of POAF and may have potential clinical utility in preventive interventions.</p

Image_2_A novel predictive model for new-onset atrial fibrillation in patients after isolated cardiac valve surgery.TIF

BackgroundPostoperative atrial fibrillation (POAF) is a severe complication after cardiac surgery and is associated with an increased risk of ischemic stroke and mortality. The main aim of this study was to identify the independent predictors associated with POAF after isolated valve operation and to develop a risk prediction model.MethodsThis retrospective observational study involved patients without previous AF who underwent isolated valve surgery from November 2018 to October 2021. Patients were stratified into two groups according to the development of new-onset POAF. Baseline characteristics and perioperative data were collected from the two groups of patients. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for the occurrence of POAF, and the results of the multivariate analysis were used to create a predictive nomogram.ResultsA total of 422 patients were included in the study, of which 163 (38.6%) developed POAF. The Multivariate logistic regression analysis indicated that cardiac function (odds ratio [OR] = 2.881, 95% confidence interval [CI] = 1.595–5.206; P ConclusionCardiac function, left atrial diameter index, operative time, neutrophil count, and fever were independent predictors of POAF in patients with isolated valve surgery. Establishing a nomogram model based on the above predictors helps predict the risk of POAF and may have potential clinical utility in preventive interventions.</p

Assembly of Diverse Spirocyclic Pyrrolidines via Transient Directing Group Enabled <i>Ortho</i>-C(sp²)–H Alkylation of Benzaldehydes

A diversity-oriented synthesis of useful spirocyclic pyrrolidines was successfully accomplished via late-stage cascade reactions of <i>o</i>-succinimide-substituted benzaldehydes. A catalytic amount of aniline as a transient directing group was efficient for the ruthenium-catalyzed <i>ortho</i>-C­(sp²)–H alkylation of benzaldehyde with maleimide. The in situ formed imine overrided a series of other traditional directing groups with excellent site selectivities. More importantly, only 0.5 mol % of ruthenium catalyst was sufficient for a 100 mmol scale-up reaction without column chromatography purification

Frequencies of ALDH2 genotypes and alleles in IS patients and PSE patients.

a<p>Adjusted for age, sex, hypertension, BMI, and drinking.</p>b<p><i>P</i> = 0.00036,</p>c<p><i>P</i> = 0.00010.</p><p>Frequencies of ALDH2 genotypes and alleles in IS patients and PSE patients.</p