Acute ischemic stroke with a diagnosis of Marfan syndrome: A report of 3 cases in multifaceted settings.

RATIONALE: Marfan syndrome (MFS), which is a dominantly inherited connective tissue disease resulting from a mutation in the FBN1 gene, exhibits variable manifestations affecting the cardiovascular, musculoskeletal, ophthalmologic, and pulmonary systems. Notably, neurologic deficiency, which involves ischemic or hemorrhagic stroke, is a rare but severe manifestation. The safety of rt-PA treatment for ischemic stroke caused by MFS is still under discussion. PATIENT CONCERNS: In the current report, we discuss 3 atypical MFS cases presented as acute ischemic stroke, compared to those exhibiting cardiovascular and musculoskeletal abnormalities. DIAGNOSES: Three patients were diagnosed with acute ischemic stroke accompanied by MFS based on clinical manifestations, imaging examinations, and genetic testings. INTERVENTIONS: The first case underwent intravenous thrombolytic therapy with rt-PA, the second case received antiplatelet therapy, and the third case received anticoagulant therapy and perfusion therapy. OUTCOMES: The neurologic deficiency of all three patients showed improvement upon discharge, and there were no symptoms of recurrence observed during the follow-up period. LESSONS SUBSECTIONS: MFS is a rare etiology in young people with embolic stroke of undetermined source. Physicians should take MFS into consideration when they observe the characteristic symptoms during a consultation. The potential pathogenesis of ischemic stroke secondary to MFS may include cardio-embolism, arterial dissection, and hypoperfusion. Although intravenous thrombolysis is a promising therapy to treat acute ischemic stroke, further examinations should be conducted to rule out contraindications in patients with a suspicion of MFS.

Association of the Neutrophil-to-Lymphocyte Ratio with 90-Day Functional Outcomes in Patients with Acute Ischemic Stroke.

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, plays an important role in the inflammatory mechanisms of the pathophysiology and progression of acute ischemic stroke (AIS). The aim of this study was to identify the potential factors associated with functional prognosis in AIS. A total of 303 AIS patients were enrolled in this study; baseline information of each participant, including demographic characteristics, medical history, laboratory data, and 90-day functional outcome, was collected. Multivariate logistic regression analysis revealed that NLR, systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were found to be independent factors for poor functional outcomes. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of the NLR for 90-day functional outcome, with the best predictive cutoff value being 3.06. In the multivariate logistic regression analysis, three models were constructed: Model 1, adjusted for age, sex, SBP, and TOAST classification (AUC = 0.694); Model 2, further adjusted for the NIHSS score at admission (AUC = 0.826); and Model 3, additionally adjusted for the NLR (AUC = 0.829). The NLR at admission was an independent predictor of 90-day prognosis in patients with AIS. The risk factors related to poor 90-day functional outcomes were higher SBP, higher NLR, and a greater NIHSS score.

Vertically-Aligned Card-House Structure for Composite Solid Polymer Electrolyte with Fast and Stable Ion Transport Channels.

All-solid-state lithium batteries (ASSLBs) are highly promising as next-generation energy storage devices owing to their potential for great safety and high energy density. This work demonstrates that composite solid polymer electrolyte with vertically-aligned card-house structure can simultaneously improve the high rate and long-term cycling performance of ASSLBs. The vertical alignment of laponite nanosheets creates fast and uniform Li+ ion transport channels at the nanosheets/polymer interphase, resulting in high ionic conductivity of 8.9 × 10-4 S cm-1 and Li+ transference number of 0.32 at 60 °C, as well as uniformly distributed solid electrolyte interphase. Such electrolyte is characterized by high mechanical strength, low flammability, excellent structural stability and stable ion transport channels. In addition, the ASSLB cell with the electrolyte and LiFePO4 cathode delivers a high discharge specific capacity of 124.8 mAh g-1 , which accounts for 85.6% of its initial capacity after 500 cycles at 1C. The reasonable design through structural control strategy by interconnecting the vertically-aligned nanosheets open a way to fabricate high performance composite solid polymer electrolytes.

Corrigendum: Improving yields by switching central metal ions in porphyrazine-catalyzed oxidation of glucose into value-added organic acids with SnO2 in aqueous solution.

[This corrects the article DOI: 10.3389/fchem.2023.1114454.].

Sesamol Alleviates High-Fat Diet-Induced Hepatic Insulin Resistance in C57BL/6 J Mice Through AMPK Activation Mediated by Adipose Adiponectin.

Sesamol is the major bioactive constituent isolated from sesame seeds and has a variety of bioactivities. However, its role and mechanism in liver insulin resistance remain unknown. The current study was designed to investigate the underlying adipose-liver crosstalk mechanism of sesamol ameliorating hepatic insulin sensitivity. The therapeutic effect of sesamol was evaluated in high-fat diet (HFD)-fed C57BL/6 J mice (100 mg/kg for 8 weeks, XYGW-2021-75) and the mechanism was further explored in HepG2 cells with/without adiponectin and adenosine 5 '-monophosphate-activated protein kinase (AMPK) inhibitor administration. Our in vivo data showed that sesamol reduced hepatic insulin resistance in HFD-induced mice with obesity by modulating protein expression levels of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and protein kinase B (AKT). Moreover, sesamol not only increased the serum and adipose tissue adiponectin concentrations but also activated the phosphorylation of AMPK in the liver. Furthermore, in vitro studies using recombinant human adiponectin and an AMPK inhibitor revealed that adiponectin and sesamol have a synergic impact on increasing glycogenesis and reducing gluconeogenesis, of which the effects could be attenuated by the AMPK inhibitor. Taken together, our results suggested that sesamol stimulated adiponectin secretion from adipocytes, whereby exhibited a co-effect on activating the downstream signal of hepatic AMPK, resulting in the alleviation of hepatic insulin resistance. The novel findings of sesamol on hepatic effects provides prospective therapeutic approaches to treat insulin resistance.

Improving yields by switching central metal ions in porphyrazine-catalyzed oxidation of glucose into value-added organic acids with SnO2 in aqueous solution.

Photocatalysis has exhibited huge potential in selective conversion of glucose into value-added chemicals. Therefore, modulation of photocatalytic material for selective upgrading of glucose is significant. Here, we have investigated the insertion of different central metal ions, Fe, Co, Mn, and Zn, into porphyrazine loading with SnO2 for access to more efficient transformation of glucose into value-added organic acids in aqueous solution at mild reaction conditions. The best selectivity for organic acids containing glucaric acid, gluconic acid, and formic acid of 85.9% at 41.2% glucose conversion was attained by using the SnO2/CoPz composite after reacting for 3 h. The effects of central metal ions on surficial potential and related possible factors have been studied. Experimental results showed that the introduction of metalloporphyrazine with different central metal ions on the surface of SnO2 has a significant effect on the separation of photogenerated charges, changing the adsorption and desorption of glucose and products on the catalyst surface. The central metal ions of cobalt and iron contributed more to the positive effects toward enhancing conversion of glucose and yields of products, and manganese and zinc contributed more to the negative effects, resulting in the poor yield of products. The differences from the central metals may attribute to the surficial potential change of the composite and the coordination effects between the metal and oxygen atom. An appropriate surficial potential environment of the photocatalyst may achieve a better interactive relationship between the catalyst and reactant, while appropriate ability of producing active species matched with adsorption and desorption abilities would gain a better yield of products. These results have provided valued ideas for designing more efficient photocatalysts in selective oxidation of glucose utilizing clean solar energy in the future.

Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21.

Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

Performance evaluation and clinical validation of optimized nucleotide MALDI-TOF-MS for mycobacterial identification.

Objective: To evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the analysis process optimized in identification of mycobacterium species. Methods: The optimized analysis process was used for mycobacterial identification in the nucleic MALDI-TOF-MS. 108 samples were used for assessing the performance of nucleic MALDI-TOF-MS, including 25 reference standards, 37 clinical isolates, 37 BALF, and 9 plasmids. The BALF of 38 patients suspected of pulmonary mycobacterial infection was collected for validation. Clinical etiological diagnosis was used as the gold standard to evaluate the diagnostic value of nucleotide MALDI-TOF-MS. Results: The sensitivity, specificity, and accuracy of the nucleotide MALDI-TOF-MS in mycobacterial identification were 96.91%, 100% and 97.22%, respectively, and the limit of detection for mycobacterium tuberculosis (MTB) was 50 bacteria/mL. Among 38 patients suspected of pulmonary mycobacterial infection, 33 were diagnosed with pulmonary tuberculosis infection, and 5 with non-mycobacterial infection. In clinical validation, the positive rates of MALDI-TOF-MS, Xpert MTB/RIF, culture and AFS in BALF of patients diagnosed with tuberculosis infection were 72.7%, 63.6%, 54.5% and 27.3%, respectively. The sensitivity/specificity of MALDI-TOF-MS, Xpert, culture and AFS in diagnosing MTB were 72.7%/100%, 63.6%/100%, 54.5%/100%, 27.3%/100%, with the areas under the curve of 0.864, 0.818, 0.773, and 0.636, respectively. Conclusion: Optimized nucleotide MALDI-TOF-MS has satisfactory sensitivity, specificity and low LOD in the identification of mycobacteria, which may serve as a potential assay for mycobacterial identification.

Global Burden of Nutritional Deficiencies among Children under 5 Years of Age from 2010 to 2019.

Under-five years of age is a critical period for children's growth and development. Nutritional deficiency during this period is associated with wasting, underweight and stunting. We aimed to conduct an epidemiological study using data derived from the GBD2019 to found the global distribution and changing trends of nutritional deficiencies among children under 5 years old, as well as the correlation between social development status and nutritional deficiencies. Nutritional deficiencies in children under 5 years has been substantially improved in the past decade; however, the progress has been unevenly distributed globally. The incidence and DALY rate decreased with the increase of socio-demographic index. In 2019, the incidence (51,872.0 per 100,000) was highest in Central Sub-Saharan Africa and the DALY rate (5597.1 per 100,000) was the highest in Western Sub-Saharan Africa. Among five subcategories of nutritional deficiencies in children under 5 years, vitamin A deficiency accounted for the largest proportion of incident cases (100,511,850, 62.1% in 2019), while the proportion of DALYs caused by protein-energy malnutrition was the highest (9,925,276, 62.0%). Nutritional deficiency in some countries remains worrisome, for whom policies guarantees and sustained efforts to control nutritional deficiencies are urgently needed.

Application of metagenomic next-generation sequencing for the diagnosis of intracranial infection of Listeria monocytogenes.

Background: Intracranial infection of Listeria monocytogenes (LM) can lead to various manifestations, including meningitis, meningoencephalitis, brainstem encephalitis, and brain abscess, which often have a poor prognosis. Metagenomic next-generation sequencing (mNGS) is a promising new tool for the diagnosis of intracranial infection of LM. We describe the typical clinical manifestations of LM intracranial infection and highlight its rarity and severity to help physicians better understand the disease characteristics. Methods: Six cases of severe LM intracranial infection were diagnosed by mNGS. We conducted a retrospective analysis of the data on disease progression, diagnostic tools, treatments, and outcomes, and summarized the findings. We compared the differences in diagnostic accuracy and timeliness between mNGS and etiological cultures. Results: Among the 6 patients, 5 were males and 1 was female (age range 32-83). Three patients had a history of immunosuppressive therapy. Common symptoms included fever (100%) and a stiff neck (100%). Coma occurred early in severe patients (66%). Two healthy young patients had previously developed with meningitis, while coma occurred in 3 immunosuppressed patients and 1 elderly patient. Three immunosuppressed patients presented with brain abscess, brainstem encephalitis, and meningitis. 1 elderly patient presented with meningitis. Two patients developed septic shock complications early. Laboratory data showed normal or slightly increased leukocytes, neutrophils, and procalcitonin, and cerebrospinal fluid (CSF) tests were consistent with bacterial CSF infection. All 6 patients were examined for blood culture and CSF culture. The positive rate of blood culture and CSF culture was 50% and 16%. The average time from admission to positive culture findings was 91 h. All 6 patients were examined for CSF mNGS. Two were also examined for whole-blood mNGS. The positive rate for CSF mNGS and whole-blood mNGS results was 100%. The mean time from admission to positive mNGS report was 47 h. After diagnosis and treatment with sensitive antibiotics, 1 patient with brain abscess developed neurological sequelae, while the other 5 patients completely recovered. Conclusions: mNGS can improve accuracy in the diagnosis of LM intracranial infection and reduce the delay in diagnosis. Intracranial infection of Listeria monocytogenes responds well to the timely use of appropriate antibiotics.

Trends in the disease burden of HBV and HCV infection in China from 1990-2019.

OBJECTIVES: This study aimed to reveal the 30-year dynamics of hepatitis B virus (HBV) and hepatitis C virus (HCV) disease burden in China from 1990-2019. METHODS: HBV/HCV data were retrieved from the Global Burden of Disease database. Joinpoint regression was used to examine temporal trends. Age-period-cohort models were applied to evaluate effects of patient age, period, and cohort on HBV/HCV-associated mortality and incidences. RESULTS: A dramatic decrease in the disease burden of HBV was found from 1990-2019, but the disease burden of HCV has remained stable since 2000. Patient age, period, and cohort exerted a significant effect on the diseases burden of HBV and HCV infection. Compared with women, men had a higher risk of HBV/HCV infections as well as HBV/HCV-associated mortality and liver cancer. Overweight, alcohol, tobacco, and drug use were important risk factors associated with HBV/HCV-associated liver cancer. The incidences of HBV- and HCV-associated liver cancer from 2019-2044 are expected to decrease by 39.4% and 33.3%, respectively. CONCLUSION: The disease burden of HBV/HCV infection has decreased in China over the past 30 years, but HBV incidences remain high, especially in men. Effective management of HBV and HCV infections is still needed for high-risk populations.

Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer's disease models.

Alzheimer's disease (AD) remains a leading cause of dementia and no therapy that reverses underlying neurodegeneration is available. Recent studies suggest the protective role of artemisinin, an antimalarial drug, in neurological disorders. In this study, we investigated the therapeutic potential of artesunate, a water-soluble derivative of artemisinin, on amyloid-beta (Aß)-treated challenged microglial BV-2, neuronal N2a cells, and the amyloid precursor protein/presenilin (APP/PS1) mice model. We found that Aß significantly induced multiple AD-related phenotypes, including increased expression/production of pro-inflammatory cytokines from microglial cells, enhanced cellular and mitochondrial production of reactive oxygen species, promoted mitochondrial fission, inhibited mitochondrial fusion, suppressed mitophagy or biogenesis in both cell types, stimulated apoptosis of neuronal cells, and microglia-induced killing of neurons. All these in vitro phenotypes were attenuated by artesunate. In addition, the over-expression of the mitochondrial fission protein Drp-1, or down-regulation of the mitochondrial fusion protein OPA-1 both reduced the therapeutic benefits of artesunate. Artesunate also alleviated AD phenotypes in APP/PS1 mice, reducing Aß deposition, and reversing deficits in memory and learning. Artesunate protects neuronal and microglial cells from AD pathology, both in vitro and in vivo. Maintaining mitochondrial dynamics and simultaneously targeting multiple AD pathogenic mechanisms are associated with the protective effects of artesunate. Consequently, artesunate may become a promising therapeutic for AD.

Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism.

Background: Globally, obesity is a significant public problem, especially when aging. Sesamol, a phenolic lignan present in sesame seeds, might have a positive effect on high-fat diet (HFD)-induced obesity associated with aging. Objective: The purpose of current research study was to explore salutary effects and mechanisms of sesamol in treating alimentary obesity and associated metabolic syndrome in middle-aged mice. Methods: C57BL/6J mice aged 4-6 weeks and 6-8 months were assigned to the young normal diet group, middle-aged normal diet group, middle-aged HFD group, and middle-aged HFD + sesamol group. At the end of experiment, glucose tolerance test and insulin tolerance test were performed; the levels of lipids and oxidative stress-related factors in the serum and skeletal muscle were detected using chemistry reagent kits; lipid accumulation in skeletal muscle was observed by oil red O staining; the expressions of muscular glucose and lipid metabolism associated proteins were measured by Western blotting. Results: Sesamol decreased the body weight and alleviated obesity-associated metabolism syndrome in middle-aged mice, such as glucose intolerance, insulin resistance, dyslipidemia, and oxidative stress. Moreover, muscular metabolic disorders were attenuated after treatment with sesamol. It increased the expression of glucose transporter type-4 and down-regulated the protein levels of pyruvate dehydrogenase kinase isozyme 4, implying the increase of glucose uptake and oxidation. Meanwhile, sesamol decreased the expression of sterol regulatory element binding protein 1c and up-regulated the phosphorylation of hormone-sensitive lipase and the level of carnitine palmityl transferase 1α, which led to the declined lipogenesis and the increased lipolysis and lipid oxidation. In addition, the SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism. Conclusions: Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism, which might be associated with the stimulation of the SIRT1/AMPK pathway.

Percutaneous Patent Foramen Ovale Closure in Patients with Cryptogenic Stroke or Transient Ischemic Attack: A Retrospective Study.

BACKGROUND: Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS). Transcatheter closure of PFO is superior to pharmacotherapy for patients with CS or transient ischemic attack (TIA). More evidence is needed to evaluate the efficacy and safety of PFO closure in Chinese patients. METHODS: This study enrolled ten CS patients and two TIA patients (mean age of 40.8 ± 9.7 y), including seven males (58%) and five females (42%) who underwent PFO closure in our center from January 2017 to July 2019. Baseline data, imaging data, and RoPE (Risk of Paradoxical Embolism) score were collected retrospectively. The preprocedural assessment and percutaneous transcatheter PFO closure were described in detail. The perioperative complications and follow-ups were recorded from all patients. RESULTS: Among ten patients with CS, eight patients had a RoPE score of >6 and two patients had a RoPE score of 6. MRI confirmed multiple infarcts in seven cases, and infarct involving the cortex in nine cases. Abnormal ECG was found in three patients and abnormal Echo in four patients. Right-to-left shunt (RLS) was detected in all the patients by cTCD or cTTE. To be specific, RLS was observed in nine of the ten TEE-detected patients. No case had PFO complicated with atrial septal aneurysm (ASA). The success rate of PFO closure was 91.6%. No serious perioperative complications were observed. During a mean time of 26.5 ± 8 months (15-41 months) of follow-up, no recurrent cerebral infarction, TIA, or thromboembolism were detected in postoperative patients. CONCLUSIONS: PFO closure is safe and effective in the treatment of Chinese patients with CS or TIA.

Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

Calcitonin Gene-Related Peptide Monoclonal Antibody Versus Botulinum Toxin for the Preventive Treatment of Chronic Migraine: Evidence From Indirect Treatment Comparison.

Background: The previously approved botulinum toxin and nowadays promising calcitonin gene-related peptide (CGRP) monoclonal antibody have shown efficacy for preventing chronic migraine (CM). However, there is no direct evidence for their relative effectiveness and safety. In this study, we conducted an indirect treatment comparison to compare the efficacy and safety of CGRP monoclonal antibody with botulinum toxin for the preventive treatment of chronic migraine. Methods: Up to August 31, 2020, we systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials (Central). Weighted mean difference (WMD) and relative risk (RR) were used to evaluate clinical outcomes. Indirect treatment comparison (ITC) software was used to conduct indirect treatment comparison. Results: Ten studies were pooled with 6,325 patients in our meta-analysis. Both botulinum toxin and CGRP monoclonal antibody demonstrated favorable efficacy in the change of migraine days, headache days, HIT-6 score, and 50% migraine responder rate compared with placebo. In indirect treatment comparison, CGRP monoclonal antibody was superior to botulinum toxin in the frequency of acute analgesics intake (WMD = -1.31, 95% CI: -3.394 to 0.774, p = 0.02113), the rate of treatment-related adverse events (AEs) (RR = 0.664, 95% CI: 0.469 to 0.939, p = 0.04047), and the rate of treatment-related serious adverse events (RR = 0.505, 95% CI: 0.005 to 46.98, p < 0.001). Conclusion: For chronic migraine patients, CGRP monoclonal antibody was slightly better than botulinum toxin in terms of efficacy and safety. In the future, head-to-head trials would be better to evaluate the efficacy and safety between different medications in the prevention of chronic migraine.

Bilobalide alleviates neuroinflammation and promotes autophagy in Alzheimer's disease by upregulating lincRNA-p21.

EGb 761 has some protective effects on AD and can improve the cognitive functions of AD mice. However, the underlying molecular mechanisms are unknown. Here, we investigated the function of bilobalide, the effective component of EGb 761, in neuroinflammation and autophagy during AD. LPS-treated BV-2 cells were used as an in vitro model for neuroinflammation. The APP/PS1 AD mouse line was used to examine the function of bilobalide in AD. ELISA and qRT-PCR were used to measure the levels of proinflammatory cytokines, including TNF-α, IL-6 and IL-1ß. Western blotting was employed to determine the protein levels of p-p65, iNOS, COX-2, LC3, beclin-1, p62 and p-STAT3. Immunostaining was applied to examine the number of autophagosomes. LPS treatment induced inflammatory responses and inhibited autophagy in BV-2 cells. Bilobalide suppressed LPS-induced neuroinflammation and promoted autophagy. Furthermore, bilobalide treatment increased the lincRNA-p21 levels, which suppressed STAT3 signalling. Knockdown of lincRNA-p21 reversed the effects of bilobalide. Overexpression of lincRNA-p21 promoted autophagy and inhibited neuroinflammation as well while STAT3 inhibitor blocked the effects of si-lincRNA-p21. In vivo experiments revealed that bilobalide improved the learning and memory capabilities of APP/PS1 AD mice. Bilobalide improves the cognitive functions of APP/PS1 AD mice. Mechanistically, bilobalide suppresses inflammatory responses and promotes autophagy possibly by upregulating lincRNA-p21 levels.

The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies.

OBJECTIVES: Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. METHODS: We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. RESULTS: Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). CONCLUSIONS: PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.

Parametric optimization and kinetic study of l-lactic acid production by homologous batch fermentation of Lactobacillus pentosus cells.

Parametric optimization always plays important roles in bioengineering systems to obtain a high product yield under the proper conditions. The parametric conditions of lactic acid production by homologous batch fermentation of Lactobacillus pentosus cells was optimized by the Box-Behnken design. The highest l-lactic acid yield was obtained as 0.836 ± 0.003 g/g glucose with the productivity of 0.906 ± 0.003 g/(L × H) under the optimum conditions of 34.7 °C, pH 6.2, 148 rpm agitation speed, and 9.3 g/L nitrogen source concentration determined by quadratic response surface with high accuracy. The adequate kinetic models of cell growth rate, lactic production rate, and glucose consumption rate were also established to describe the fermentation behavior of L. pentosus cells with the correlation coefficients of 09985, 0.9990, and 0.9989, respectively.

Association Between Plasma Lipoprotein-Associated Phospholipase A2 and Plaque Vulnerability in TIA Patients With Unilateral Middle Cerebral Artery Stenosis.

Background: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as a novel biomarker for coronary atherosclerosis. However, the association between Lp-PLA2 and plaque vulnerability in atherosclerosis of cervicocerebral arteries remains poorly defined, especially for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the association between Lp-PLA2 and plaque vulnerability in transient ischemic attack (TIA) patients with unilateral middle cerebral artery stenoses (MCAs). Methods: In this study, a total of 207 patients were enrolled from April 2017 to April 2020. Clinical data were collected, and MCA plaques were examined with high-resolution magnetic resonance imaging (HRMRI). Baseline characteristics of patients were collected during hospitalization. Statistical comparisons were performed using Pearson's chi-squared test, Mann-Whitney U test, and the Breslow-Day/Tarone's test for the determination of heterogeneity in different age strata. Multivariate binary logistic analysis was used to investigate the potential independent predictors that were highly correlated to plaque vulnerability. Results: The results showed that a high Lp-PLA2 level (>221 ng/ml) was associated with plaque vulnerability in TIA patients with unilateral MCAs. High Lp-PLA2 was independently associated with plaque vulnerability in patients ≤ 60 years old [multivariate adjusted odds ratio (OR) = 9.854; 95% CI, 2.458-39.501] but not in patients >60 years old (multivariate adjusted OR = 1.901; 95% CI, 0.640-5.650). Predictors of plaque vulnerability in different age strata were also different. Conclusion: Lp-PLA2 levels may be correlated to plaque vulnerability in TIA patients with unilateral MCAs and might be a diagnostic biomarker for plaque vulnerability in this kind of patients, especially for ones aged ≤ 60 years old.