Early blood pressure lowering therapy is associated with good functional outcome in patients with intracerebral hemorrhage.

BACKGROUND: The implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients. METHODS: We included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses. RESULTS: A total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03-2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08-3.76; P = 0.027). CONCLUSIONS: In ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

High-efficiency liquid luminescent solar concentrator based on CsPbBr3 quantum dots.

The performance degradation is still a challenge for the development of conventional polymer luminescent solar concentrator (LSC). Liquid LSC (L-LSC) may be an alternative due to polymerization-free fabrication. Here, we have prepared a CsPbBr3 quantum dots (QDs)-based L-LSC by injecting the QDs solution into a self-assembly quartz glass mold. The as-fabricated L-LSC performance is evaluated by optical characterization and photo-electrical measurement. The external quantum efficiency of the L-LSC is up to 13.44%. After coupling the commercial solar cell, the optimal optical efficiency reaches 2.32%. These results demonstrate that L-LSC may provide a promising direction for advanced solar light harvesting technologies.

A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients.

BACKGROUND: A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA). METHODS: We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot. RESULTS: A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score ≥ 13, and onset-to-treatment time (OTT) ≥ 180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221-0.9904, P < 0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores. CONCLUSIONS: This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score ≥ 13, and OTT ≥ 180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.

Next-Generation Glycan Microarray Enabled by DNA-Coded Glycan Library and Next-Generation Sequencing Technology.

Interactions of glycans with proteins, cells, and microorganisms play important roles in cell-cell adhesion and host-pathogen interaction. Glycan microarray technology, in which multiple glycan structures are immobilized on a single glass slide and interrogated with glycan-binding proteins (GBPs), has become an indispensable tool in the study of protein-glycan interactions. Despite its great success, the current format of the glycan microarray requires expensive, specialized instrumentation and labor-intensive assay and image processing procedures, which limit automation and possibilities for high-throughput analyses. Furthermore, the current microarray is not suitable for assaying interaction with intact cells due to their large size compared to the two-dimensional microarray surface. To address these limitations, we developed the next-generation glycan microarray (NGGM) based on artificial DNA coding of glycan structures. In this novel approach, a glycan library is presented as a mixture of glycans and glycoconjugates, each of which is coded with a unique oligonucleotide sequence (code). The glycan mixture is interrogated by GBPs followed by the separation of unbound coded glycans. The DNA sequences that identify individual bound glycans are quantitatively sequenced (decoded) by powerful next-generation sequencing (NGS) technology, and copied numbers of the DNA codes represent relative binding specificities of corresponding glycan structures to GBPs. We demonstrate that NGGM generates glycan-GBP binding data that are consistent with that generated in a slide-based glycan microarray. More importantly, the solution phase binding assay is directly applicable to identifying glycan binding to intact cells, which is often challenging using glass slide-based glycan microarrays.

The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment.

BACKGROUND AND PURPOSE: Various types of cerebral small vessel diseases (CSVD) are commonly coexisting and the clinical outcome possibly is determined by their combined effect. The present study was designed to explore the possible relationship between the global burden of CSVD and clinical outcomes after recombinant tissue plasminogen activator (rt-PA) treatment of ischemic stroke. METHODS: We enrolled patients with acute ischemic stroke (AIS) after IV rt-PA treatment between August 2016 and July 2018. According to the total burden rating scale of CSVD, we calculated the total CSVD score for white matter hyperintensities, lacunar infarction, cerebral microbleeds, and perivascular spaces. All patients were assessed on the basis of the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score at 90 days after stroke. We used multivariate logistic regression analysis to examine the associations between global burden of CSVD and degree of neurological deficit and clinical outcomes. ROC curve analysis was used to determine cut-off values of the total CSVD score in predicting poor outcomes. RESULTS: The results showed that the total CSVD score was independently associated with moderate to severe stroke (OR 2.187, 95%CI 1.495-3.119, P < 0.001). Initial NIHSS (OR 1.23, 95%CI 1.144-1.330, P < 0.001), OTT (OR 1.007, 95%CI 1.000-1.014, P = 0.037), and CSVD score (OR 3.157, 95%CI 2.120-4.703, P < 0.001) was significantly related to poor functional outcome at 3 months. The total CVSD score cut-off value of 1.5 was determined at best to distinguish between good prognosis and poor outcome (AUC 0.7534 [95%CI 0.6883-0.8185]). CONCLUSIONS: The global burden of CSVD was independently associated with neurological deficit severity and clinical outcomes of AIS after IV rt-PA treatment. The total CVSD score is a reliable predictor for poor outcomes of AIS after IV rt-PA treatment.

Effects of capsaicin on swallowing function in stroke patients with dysphagia: A randomized controlled trial.

BACKGROUND/AIMS: Dysphagia is a common complication after acute stroke. While there are several innovative treatments being tested to improve the swallowing function of stroke patients with dysphagia, our aim is to explore the use of readily available natural capsaicin in stroke patients with dysphagia. STUDY DESIGN: A randomized, double-blind study. METHODS: Sixty-nine hospitalized stroke patients were enrolled in this study. The capsaicin intervention group received thermal tactile stimulation with supplementation of natural capsaicin and additional nectar viscosity boluses. The control group received stimulation and boluses with placebo. Swallowing function was evaluated before and after the 3-week treatment, using Volume-Viscosity Swallow Test, Eating Assessment Tool, Standardized Swallowing Assessment, and Water Swallow Test. RESULTS: The score decreases in the Eating Assessment Tool and Standardized Swallowing Assessment of the capsaicin intervention group were significantly greater than that of the placebo control group (P < .01). Among the 60 patients, the capsaicin intervention group exhibited effectiveness in a higher number of patients (n = 27, 90%) than the placebo group (n = 9, 30%, P < .001). CONCLUSIONS: Regular use of natural capsaicin could promote the recovery of swallow function in stroke patients with dysphagia. The ample availability of natural capsaicin could provide a low cost, easily accessible, and safe alternative method to address dysphagia in stoke patients.

Anthranilic Acid as a Versatile Fluorescent Tag and Linker for Functional Glycomics.

The advancement of glycoscience is critically dependent on the access to a large number of glycans for their functional study. Naturally occurring glycans are considered a viable source for diverse and biologically relevant glycan libraries. A mixture of free reducing glycans released from natural sources can be fluorescently tagged and separated by chromatography to produce a natural glycan library. Anthranilic acid (AA) has been widely used to fluorescently tag reducing glycans for HPLC or LC/MS analysis. However, AA conjugated glycans are not efficiently immobilized on microarray slides due to the lack of a primary alkylamine functional group. In this study, we have developed simple and efficient chemistry for bioconjugation and further functionalization of glycan-AA conjugates. This new approach enables quick preparation of glycan microarrays and neoglycoproteins from glycan-AA conjugates, which can be separated by weak anion exchange (WAX) and C18 reversed-phase HPLC.

Association of aspirin use with risk of intracerebral hemorrhage in patients without history of stroke or transient ischemic attack in the UK Biobank.

BACKGROUND: The association between aspirin use and the risk of intracerebral hemorrhage (ICH) among individuals without previous stroke events is inconclusive. AIM: We investigated the association between regular aspirin use and ICH risk in middle-aged and older adults without previous stroke or transient ischemic attack (TIA). METHODS: This prospective population-based study included participants older than 40 years with no history of stroke or TIA from the UK Biobank. The main exposure was regular aspirin use. Cox regression analyses and propensity score matching analyses estimated the hazard ratios (HRs) for aspirin use for incident fatal and non-fatal ICH. We conducted pre-specified subgroup analyses for selecting individuals at high risk of ICH when using aspirin. Multiple sensitivity analyses were performed to test the robustness of our results. RESULTS: A total of 449,325 participants were included into final analyses (median (IQR) age 58 (50-63) years, 54.6% females), of whom 58,045 reported aspirin use. During a median follow-up of 12.75 (IQR: 12.03-13.47) years, 1557 (0.3%) incident ICH cases were identified, of which 399 (25.6%) were fatal. Aspirin was not associated with increased risk of overall (hazard ratio (HR): 1.11, 95% confidence interval (CI): 0.95-1.27, P = 0.188), fatal (HR: 1.03, 95% CI: 0.78-1.36, P = 0.846) and non-fatal (HR: 1.12, 95% CI: 0.95-1.33, P = 0.186) ICH. Propensity score matching analysis showed similar results. Subgroup analysis indicated that aspirin use in individuals older than 65 years or with concurrent anticoagulant use was correlated with increased risk of ICH. CONCLUSION: In this large cohort study of middle-aged and older adults without stroke or TIA events, there was no significant association between aspirin use and ICH risk in the real-world setting. However, it is possible that aspirin use in those aged over 65 years and concurrent anticoagulant treatment may increase the risk of ICH.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

The synchronous upregulation of a specific protein cluster in the blood predicts both colorectal cancer risk and patient immune status.

BACKGROUND: Early detection and treatment of colorectal cancer (CRC) is crucial for improving patient survival rates. This study aims to identify signature molecules associated with CRC, which can serve as valuable indicators for clinical hematological screening. METHOD: We have systematically searched the Human Protein Atlas database and the relevant literature for blood protein-coding genes. The CRC dataset from TCGA was used to compare the acquired genes and identify differentially expressed molecules (DEMs). Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify modules of co-expressed molecules and key molecules within the DEMs. Signature molecules of CRC were then identified from the key molecules using machine learning. These findings were further validated in clinical samples. Finally, Logistic regression was used to create a predictive model that calculated the likelihood of CRC in both healthy individuals and CRC patients. We evaluated the model's sensitivity and specificity using the ROC curve. RESULT: By utilizing the CRC dataset, WGCNA analysis, and machine learning, we successfully identified seven signature molecules associated with CRC from 1478 blood protein-coding genes. These markers include S100A11, INHBA, QSOX2, MET, TGFBI, VEGFA and CD44. Analyzing the CRC dataset showed its potential to effectively discriminate between CRC and normal individuals. The up-regulated expression of these markers suggests the existence of an immune evasion mechanism in CRC patients and is strongly correlated with poor prognosis. CONCLUSION: The combined detection of the seven signature molecules in CRC can significantly enhance diagnostic efficiency and serve as a novel index for hematological screening of CRC.

Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

Improving Functional Muscle Regeneration in Volumetric Muscle Loss Injuries by Shifting the Balance of Inflammatory and Pro-Resolving Lipid Mediators.

Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formation, persistent pain, and permanent functional deficits. The aberrant healing response is preceded by acute inflammation and immune cell infiltration which does not resolve. We analyzed the biosynthesis of inflammatory and specialized pro-resolving lipid mediators (SPMs) after VML injury in two different models; muscle with critical-sized defects had a decreased capacity to biosynthesize SPMs, leading to dysregulated and persistent inflammation. We developed a modular poly(ethylene glycol)-maleimide hydrogel platform to locally release a stable isomer of Resolvin D1 (AT-RvD1) and promote endogenous pathways of inflammation resolution in the two muscle models. The local delivery of AT-RvD1 enhanced muscle regeneration, improved muscle function, and reduced pain sensitivity after VML by promoting molecular and cellular resolution of inflammation. These findings provide new insights into the pathogenesis of VML and establish a pro-resolving hydrogel therapeutic as a promising strategy for promoting functional muscle regeneration after traumatic injury.

Ultraearly Intraventricular Hemorrhage Growth Predicts Early Neurologic Deterioration and Poor Functional Outcome After Acute Intracerebral Hemorrhage.

Background The presence of intraventricular hemorrhage (IVH) was extensively investigated and was associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the effect of the speed of ventricular bleeding on outcomes is unknown. Methods and Results We prospectively included patients with ICH who had baseline computed tomography scans within 6 hours after ictus between January 2016 and October 2021. The clinical characteristics were compared between patients with and without early neurologic deterioration (END). Ultraearly IVH growth (uIVHG) was defined as baseline IVH volume by onset-to-imaging time. The association between uIVHG and outcomes was assessed by using multivariable logistic regression analysis. We established the ultraearly IVH growth (uIVH) score and compared the areas under the receiver operating characteristic curves of the existing scores for predicting END. A total of 299 patients were finally enrolled. Of those, 38 patients (12.7%) experienced END at 24 hours and 89 patients (29.8%) had poor outcomes at 90 days. After adjustment for confounding factors, uIVHG (odds ratio, 1.061 [95% CI, 1.011-1.113]; P=0.016) was independently associated with END in multivariable analysis. A prediction score was developed on the basis of the logistic model. The uIVH score was developed as a sum of individual points (0-6) based on age, hematoma volume, National Institutes of Health Stroke Scale, hematoma expansion, and uIVHG ≥2.5 mL/h. In comparison with the ICH score and modified Emergency Department ICH Scale, the uIVH score exhibited best performance in the prediction of END. Conclusions uIVHG is associated with early neurologic deterioration and poor functional outcome in patients with ICH.

Age-related differences in risk factors, clinical characteristics, and outcomes for intracerebral hemorrhage.

Background and purpose: Intracerebral hemorrhage (ICH) is a severe form of stroke that remains understudied in the young adults. We aimed to investigate the clinical presentation, and risk factors associated with ICH in this age group and compare them to older patients. Methods: Our study included ICH patients admitted between March 2016 and December 2021 in the First Affiliated Hospital of Chongqing Medical University from our ongoing prospective cohort database. Demographic characteristics, etiology, risk factors, and clinical outcomes were compared between elderly and young patients. Furthermore, logistic regression analysis was employed to explore risk factors associated with the functional outcome at 3-months. Results: We selected 1,003 patients (mean age, 59.9 ±13.8 years old), 746 (74.4%) patients were aged >50 years. The logistic regression analysis showed young patients have a higher proportion of secondary ICH, higher white blood cell count and higher body mass index (BMI), but less diabetes mellitus. Of all patients, predictors of 3-month functional independence was first-ever ICH and age ≤50 years. The history of nephropathy and stroke, higher baseline NIHSS score, larger hematoma volume, and the presence of hydrocephalus were associated with poor outcomes. And the white blood cell count could significantly influence the prognosis among young ICH patients. Three-month functional outcome based on modified Rankin scale score was better in young patients than the elderly (OR, 1.232; 95% CI, 1.095-1.388; p < 0.001). Conclusions: The highest incidence of ICH occurs in the age groups of 50-59 and 60-69. ICH in young adults had higher white blood cell and BMI compared to the elderly, and differs in etiological distribution. The young patients also had similar short-term mortality but more favorable functional outcomes than the elderly. Furthermore, NIHSS score and larger hematoma volumes were associated with poor outcome in all patients.

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19.

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

Enhanced luminescence via energy transfer from Ag+ to RE ions (Dy3+, Sm3+, Tb3+) in glasses.

Oxyfluoride glasses containing Ag species and rare earth (RE) ions (Dy(3+), Sm(3+), Tb(3+)) were prepared by melt-quenching technique. The type of luminescent species of novel excitation band (230-300 nm peaked at 255 nm) and emission band (300-600 nm peaked at 350 nm) were investigated by absorption, excitation, emission spectra, as well as decay lifetime measurements and can be ascribed to isolated Ag(+) ions. Owing to energy transfer from Ag(+) to RE ions, significant enhancements of RE ions emission (76 times for Sm(3+), 41 times for Dy(3+)) were observed for non-resonant UV excitation (255 nm). Our research may extend the understanding of interactions between RE ions and Ag species.

Tunable white luminescence and energy transfer in (Cu+)2, Eu3+ codoped sodium silicate glasses.

Luminescent properties of (Cu+)2, Eu3+ single-doped and codoped sodium silicate glasses were systematically investigated by excitation spectra, emission spectra, and decay curves. Due to the efficient energy transfer from (Cu+)2 pairs to Eu3+, varied hues from green to yellowish white and eventually to orange were generated by tuning the content of Eu3+. A perfect white-light emission with CIE coordinates (X=0.336,Y=0.346) was realized in (Cu+)2, Eu3+ and Ce3+ codoped samples. Our research indicates the potential application of (Cu+)2, Eu3+ codoped sodium silicate glasses for converting phosphors for UV LED chips to generate white LEDs.

Sb3+/Mn2+ co-doped tunable white emitting borosilicate glasses for LEDs.

Luminescent properties of Sb(3+)/Mn(2+) co-doped borosilicate glasses containing no rare earth ions were systematically investigated through absorption, excitation, emission spectra, and decay curves. Upon 250-340 nm light excitation, the glasses exhibit broad blue emission at 400 nm (Sb(3+)) and red emission at 615 nm (Mn(2+)). The varied emitted color from blue through white and eventually to red can be obtained by properly tuning the content of Mn(2+) ions due to energy transfer from Sb(3+) to Mn(2+). Our investigation shows that Sb(3+)/Mn(2+) co-doped glasses may provide a new platform to design and fabricate luminescent materials for UV LED chips in the future.

Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway.

It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid, 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting. Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas, as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor, compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.