Incongruent gray matter atrophy and functional connectivity of striatal subregions in behavioral variant frontotemporal dementia.

Previous studies on the striatum demonstrated that it is involved in the regulation of cognitive function and psychiatric symptoms in patients with behavioral variant frontotemporal dementia (bvFTD). Multiple lines of evidence have shown that striatal subregions have their own functions. However, the results of the existing studies on striatal subregions are inconsistent and unclear. In this study, we found that structural imaging analysis revealed that the bvFTD patients had smaller volumes of striatal subregions than the controls. We found that the degree of atrophy varied across the striatal subregions. Additionally, the right striatal subregions were significantly more atrophic than the left in bvFTD. Functional imaging analysis revealed that bvFTD patients exhibited different changed patterns of resting-state functional connectivity (RSFC) when striatal subregions were selected as regions of interest (ROI). The RSFC extending range on the right ROIs was more significant than on the left in the same subregion. Interestingly, the RSFC of the subregions extending to the insula were consistent. In addition, the left dorsolateral putamen may be involved in executive function regulation. This suggests that incongruence in striatal subregions may be critical to the bvFTD characteristics.

Co-occurrence of depressive and anxious symptoms and their influence on self-rated health: a national representative survey among Chinese older adults.

OBJECTIVES: The prevalence of the co-occurrence of depressive and anxious symptoms (CO) and their influence on perceived overall health were not clear in community dwelling Chinese older adults. The aims of the study were to investigate the prevalence of CO and to explore its influence on self-rated health (SRH). METHOD: This study included 12301 individuals aged ≥65 years from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationally representative survey of older adults in mainland China. Participants received face-to-face interviews and assessments of depressive symptoms and anxious symptoms via 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), respectively. SRH was measured by self-reported. A logistic regression model was used to examine the association between CO and SRH after adjusting for confounding variables. RESULTS: The average age was 83.4 (SD: 11.0) years and there were 6576 (53.5%) females. The age- and sex-standardized prevalence of depressive symptoms only (DSO) was 38.6%, anxious symptoms only (ASO) was 1.5%, and CO was 10.8%. Compared with those without depressive and anxious symptoms, the older adults with DSO or ASO were more likely to have significant influence on SRH. And particularly, CO was likely to produce the greatest decrement in the level of SRH. CONCLUSION: CO was not rare in Chinese older adults nationwide. The older adults having CO had increased risk for lower level of SRH than having DSO or ASO. More attention should be given to CO among the older adults.

Diagnosis of membranous supravalvular aortic stenosis with severe aortic valve insufficiency.

Although the clinical manifestations of membranous supravalvular aortic stenosis (SVAS) are distinctive, its diagnosis remains challenging. Failure to initiate surgical treatment in a timely manner greatly increases the risk of sudden cardiac death. We report a case of membranous SVAS, detailing the clinical presentation and imaging manifestations.

Frequency and molecular basis of CD36 deficiency among platelet donors in Kunming, China.

CD36 is a multifunctional receptor expressed on the surface of many cell types. Among healthy individuals, CD36 may be absent on platelets and monocytes (type I deficiency) or platelets alone (type II deficiency). However, the exact molecular mechanisms underlying CD36 deficiency remain unclear. In this study, we aimed to identify individuals with CD36 deficiency and investigate the molecular basis underlying it. Blood samples were collected from platelet donors at Kunming Blood Center. Platelets and monocytes were isolated and CD36-expression levels were analyzed using flow cytometry. DNA from whole blood and mRNA isolated from monocytes and platelets of individuals with CD36 deficiency were analyzed using polymerase chain reaction (PCR) testing. The PCR products were cloned and sequenced. Among the 418 blood donors,7 (1.68%) were CD36 deficient: 1 (0.24%) with type I deficiency and 6(1.44%) with type II deficiency. Six heterozygous mutations occurred, including c.268C>T (in type I individuals), c.120 + 1 G>T, c.268C>T, c.329_330del/AC, c.1156 C>T, c.1163A>C, and c.1228_1239del/ATTGTGCCTATT (in type II individuals). Mutations were not detected in one type II individual . At the cDNA level, only mutant, but not wild-type, transcripts were detected in the platelets and monocytes of type I individual. In type II individuals, only mutant transcripts were found in platelets, whereas monocytes possessed wild-type and mutant transcripts. Interestingly, only alternative splicing transcripts were observed in the individual without mutation. We report the incidence rates of type I and II CD36 deficiencies among platelet donors in Kunming. Molecular genetic analyses of DNA and cDNA demonstrated that homozygous mutations on the cDNA level in platelets and monocytes or platelets alone identified type I and II deficiencies, respectively. Furthermore, alternatively spliced products also potentially contribute to the mechanism of CD36 deficiency.

What is the context? Healthy individuals may lack CD36 on platelets and (or) monocytes, which are defined as Type I and Type II CD36 deficiency. These individuals could develop anti-CD36 antibodies associated with immune-mediated disorders. However, the mechanism underlying the CD36 deficiency is still unclear. In this study, we reported the incidence of CD36 deficiency in Kunming platelet donors and found the new molecular basis of CD36 deficiency individuals.What's new? Molecular genetic analysis of cDNA derived from type I subjects showed the presence of mutant transcript only, both in platelets and monocytes. In type II subjects, platelets only carry mutant transcript, whereas monocytes possessed both wild-type and mutant transcripts. Furthermore, we found that alternatively spliced product of CD36 transcript could also contribute to the mechanism of CD36 deficiencies.What's the impact? Our finding indicates that analysis of CD36 at cDNA level is mandatory to verify different forms of CD36 deficiencies. This information may help us to understand the development of anti-CD36 antibodies in CD36 deficient individuals.

Comparative Analysis of Laparoscopic Pancreatoduodenectomy in Elderly Patients: Safety, Efficacy, and Cost Evaluation.

BACKGROUND The use of laparoscopic pancreatoduodenectomy in elderly patients has sparked debate due to concerns about its safety. This study evaluates its safety and efficacy for elderly patients. MATERIAL AND METHODS We retrospectively analyzed data from 250 patients who underwent pancreatoduodenectomy between January 2015 and April 2022. Group A consisted of 100 non-elderly patients (under 70) who had laparoscopic procedures; Group B had 60 elderly patients (70 and above) with laparoscopic surgeries; and Group C included 90 elderly patients with open surgeries. Clinical outcomes were then compared across the groups. RESULTS Elderly patients undergoing laparoscopic pancreatoduodenectomy experienced a higher conversion rate (35% vs 19%), increased ICU admissions post-operation (45% vs 23%), a prolonged ICU stay, greater hospital expenses (¥118,782.48 vs ¥106,698.38), and a lower post-operative adjuvant therapy rate (31.91% vs 69.23%). However, they had fewer B-C pancreatic fistulas (5% vs 24%). Compared to open surgery in elderly patients, laparoscopic procedure showed benefits such as reduced blood loss (median of 200 ml) and fewer wound infections (3.33% vs 17.78%). On the downside, laparoscopy had a longer operation time (462.5 minutes vs 315 minutes), took longer before patients could resume oral intake (median of 5.5 days vs 5 days), and incurred higher hospitalization costs (¥118,782.48 vs ¥111,541.60). CONCLUSIONS While laparoscopic pancreatoduodenectomy in elderly patients may not match the outcomes seen in younger patients, it doesn't possess marked drawbacks when compared to open surgery. It is a safe and viable option for the elderly.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

The confusing pelvic cystic mass: A case of giant prostatic utricle cyst diagnosed by ultrasound.

The giant prostatic utricle cyst, located behindthe bladder with removable irregular mixed echo, communicating with the urethraat the level of the seminal colliculus, was diagnosed by ultrasound andverified by pathology and surgery.

Multimodal imaging of morning glory syndrome with persistent hyperplastic primary vitreous.

Morning glory syndrome (MGS) and persistent hyperplastic primary vitreous (PHPV) are congenital abnormity, which may be related to the increased incidence of systemic abnormalities and retinal detachment，diagnosed by ultrasound, identified by CT, MRI, and with the confirmation of fundus examination.

Comprehensive characterization of Guanosine monophosphate synthetase in Nicotiana tabacum.

BACKGROUND: Guanosine monophosphate (GMP) synthetase is an enzyme that converts xanthosine monophosphate to GMP. GMP plays an essential role in plant development and responses to internal and external stimuli. It also plays a crucial role in several plant physiochemical processes, such as stomata closure, cation flux regulation, pathogen responses and chloroplast development. METHODS AND RESULTS: The mRNA sequences of NtGMP synthase in tobacco (Nicotiana tabacum) were rapidly amplified from cDNA. The GMP synthase open reading frame contains a 1617 bp sequence encoding 538 amino acids. A sequence analysis showed that this sequence shares high homology with that of Nicotiana sylvestris, Nicotiana attenuata, N. tomentosiformis, Solanum tuberosum, Lycopersicon pennellii, L. esculentum, Capsicum annuum, C. chinense and C. baccatum GMP synthase. A BLAST analysis with a tobacco high-throughput genomic sequence database revealed that the tobacco GMP synthase gene has five introns and six exons. A phylogenetic analysis showed a close genetic evolutionary relationship with N. sylvestris GMP synthase. The tissue-specific expression profile was evaluated using quantitative real-time PCR. The data showed that NtGMP synthase was highly expressed in leaves and moderately expressed in roots, flowers, and stems. The subcellular localization was predicted using the WOLF PSORT webserver, which strongly suggested that it might be localized to the cytoplasm. CONCLUSIONS: In the current study, we cloned and comprehensively characterized GMP synthase in tobacco (Nicotiana tabacum). Our results establish a basis for further research to explore the precise role of this enzyme in tobacco.

A new Graph Gaussian embedding method for analyzing the effects of cognitive training.

Identifying heterogeneous cognitive impairment markers at an early stage is vital for Alzheimer's disease diagnosis. However, due to complex and uncertain brain connectivity features in the cognitive domains, it remains challenging to quantify functional brain connectomic changes during non-pharmacological interventions for amnestic mild cognitive impairment (aMCI) patients. We present a quantitative method for functional brain network analysis of fMRI data based on the multi-graph unsupervised Gaussian embedding method (MG2G). This neural network-based model can effectively learn low-dimensional Gaussian distributions from the original high-dimensional sparse functional brain networks, quantify uncertainties in link prediction, and discover the intrinsic dimensionality of brain networks. Using the Wasserstein distance to measure probabilistic changes, we discovered that brain regions in the default mode network and somatosensory/somatomotor hand, fronto-parietal task control, memory retrieval, and visual and dorsal attention systems had relatively large variations during non-pharmacological training, which might provide distinct biomarkers for fine-grained monitoring of aMCI cognitive alteration. An important finding of our study is the ability of the new method to capture subtle changes for individual patients before and after short-term intervention. More broadly, the MG2G method can be used in studying multiple brain disorders and injuries, e.g., in Parkinson's disease or traumatic brain injury (TBI), and hence it will be useful to the wider neuroscience community.

Decreased exosome-delivered miR-486-5p is responsible for the peritoneal metastasis of gastric cancer cells by promoting EMT progress.

BACKGROUND: The present study aims to investigate the preliminary mechanism underlying the peritoneal metastasis of gastric cancer cells. METHODS: Exosomes from GC9811 cells (Con-Exo) and from GC9811-P cells (PM-Exo) were extracted by ultracentrifugation, which were identified with transmission electron microscopy (TEM) and nanoparticle trafficking analysis, as well as the expression of CD9, CD63, and CD81 detected by Western blot assay. α-SMA expression was determined by immunofluorescence assay and Western blot assay. The levels of Snail1, E-cadherin, and Actin-related protein 3 (ACTR3) were evaluated by Western blot assay. MiRNA array was performed on exosomes to screen the differentially expressed miRNAs. The expressions of miRNAs, SMAD2, CDK4, and ACTR3 were determined by QRT-PCR. The delivery of miR-486-5p was confirmed by laser confocal detection. RESULTS: Firstly, TEM, nanoparticle trafficking analysis, and Western blot assays were used to confirm the successful extraction of Con-Exo and PM-Exo. The incubation of Con-Exo and PM-Exo could decrease E-cadherin expression and increase of α-SMA respectively in HMrSV5 cells, with the increased proportion of fusiform cells. More significant changes were observed in PM-Exo-treated HMrSV5 cells. Secondary, compared to Con-Exo, miR-486-5p and miR-132-3p were found downregulated, and miR-132-5p was found upregulated in PM-Exo. The transfection of miR-486-5p and miR-132-3p was observed to suppress EMT, and the transfection of miR-132-3p was observed to induce EMT. Laser confocal detection confirmed the delivery of miR-486-5p from gastric cancer cells to HMrSV5 cells through exosomes. Lastly, the expression of Mothers against decapentaplegic homolog 2 (SMAD2), cyclin-dependent kinase 4 (CDK4), and ACTR3 was found to be downregulated via miR-486-5p. CONCLUSION: Decreased delivery of miR-486-5p via exosomes might be responsible for the peritoneal metastasis of gastric cancer cells by promoting epithelial-mesenchymal transition progress.

Influence of More Than 5 Years of Continuous Exposure to Antipsychotics on Cerebral Functional Connectivity of Chronic Schizophrenia.

OBJECTIVE: To explore the effect of long-term antipsychotics use on the strength of functional connectivity (FC) in the brains of patients with chronic schizophrenia. METHOD: We collected resting-state functional magnetic resonance imaging from 15 patients with continuously treated chronic schizophrenia (TCS), 19 patients with minimally TCS (MTCS), and 20 healthy controls (HCs). Then, we evaluated and compared the whole-brain FC strength (FCS; including full-range, short-range, and long-range FCS) among patients with TCS, MTCS, and HCs. RESULTS: Patients with TCS and MTCS showed reduced full-/short-range FC compared with the HCs. No significant differences in the whole-brain FCS (including full-range, short-range, and long-range FCS) or clinical characteristics were identified between patients with TCS and MTCS. Additionally, the FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus negatively correlated with the duration of illness and positively correlated with onset age across all patients with chronic schizophrenia. CONCLUSIONS: Regardless of the long-term use of antipsychotics, patients with chronic schizophrenia show decreased FC compared with healthy individuals. For some patients with chronic schizophrenia, the influence of long-term and minimal/short-term antipsychotic exposure on resting-state FC was similar. The decreased full- and short-range FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus may be an ongoing pathological process that is not altered by antipsychotic interventions in patients with chronic schizophrenia. Large-sample, long-term follow-up studies are still needed for further exploration.

Characteristics of Cognitive Deficit in Amnestic Mild Cognitive Impairment With Subthreshold Depression.

It is widely recognized that depression may precipitate the incidence of dementia in the elderly individuals and individuals with amnestic mild cognitive impairment (aMCI) in particular. However, the association between subthreshold depression (SD) and cognitive deficits in patients with aMCI remains unclear. To address this, we collected demographic information and conducted a battery of neuropsychological cognitive assessments in 33 aMCI participants with SD (aMCI/SD+), 33 nondepressed aMCI participants (aMCI/SD-), and 53 normal controls (NC). Both aMCI groups showed significantly poorer performance in most cognitive domains relative to the NC group (ie, memory, language, processing speed, and executive function). Notably, the aMCI/SD+ group showed significantly poorer attention/working memory compared with the aMCI/SD- group. Multiple linear regression analyses revealed a significant negative association between the severity of depressive symptoms and attention/working memory capacity (ß = - .024, P = .024), accounting for 8.28% of the variations in this cognitive domain. All statistical analyses were adjusted by age, sex, and years of education. A logistic regression model had an accuracy of 72.4% in discriminating between the aMCI/SD+ and aMCI/SD- groups based on individual cognitive profiles over 6 domains. Our findings indicate that patients with aMCI with and without SD have distinct patterns of cognitive impairment. This finding may facilitate the diagnosis and treatment of SD in patients with aMCI.

A randomized controlled trial of a mobile application-assisted nurse-led model used to improve treatment outcomes in children with asthma.

AIM: To evaluate the effectiveness of a mobile application-assisted nurse-led management model in childhood asthma. BACKGROUND: Studies have shown that a nurse-led asthma management model can improve asthma outcomes. However, the role of a mobile application-assisted nurse-led model in paediatric asthma management has not been studied well. DESIGN: A multi-centre randomized clinical trial. METHODS: The trial was conducted between March 2017-March 2018. A total of 152 children (6 to 11.9 years old) were enrolled, with 77 children in the experimental group and 75 in the control group. All children received nurse-led asthma management and other routine treatment measures, including inhaled corticosteroids. Meanwhile, a mobile application was used to manage asthma only for children in the experimental group. Primary outcome was frequency of asthma exacerbations. All outcomes were evaluated twice a month for 12 months. RESULTS: Compared with the pre-enrollment period, frequency of asthma exacerbations decreased in the post-enrollment period in the two groups, with a greater decrease in the experimental group. Compared with children in the control group, children in the experimental group had better secondary outcomes, such as improved adherence, higher Childhood Asthma Control Test scores, decreased respiratory tract infections, days of antibiotic use, days of school absence, parental work loss, and medical expenses. CONCLUSION: A mobile application-assisted nurse-led management model decreased asthma exacerbations and improved secondary outcomes in children with asthma. Further research is needed to verify its validity in larger population samples. IMPACT: Children with asthma benefited from a nurse-led asthma management model when combined with mobile application. This trial suggested that computer and Internet technologies should be incorporated into nurse-led asthma strategy in paediatric asthma management. TRIAL REGISTRATION: The current trial was registered online with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016726).

Ultrahigh Mass Activity for Carbon Dioxide Reduction Enabled by Gold-Iron Core-Shell Nanoparticles.

Wide application of carbon dioxide (CO2) electrochemical energy storage requires catalysts with high mass activity. Alloy catalysts can achieve superior performance to single metals while reducing the cost by finely tuning the composition and morphology. We used in silico quantum mechanics rapid screening to identify Au-Fe as a candidate improving CO2 reduction and then synthesized and tested it experimentally. The synthesized Au-Fe alloy catalyst evolves quickly into a stable Au-Fe core-shell nanoparticle (AuFe-CSNP) after leaching out surface Fe. This AuFe-CSNP exhibits exclusive CO selectivity, long-term stability, nearly a 100-fold increase in mass activity toward CO2 reduction compared with Au NP, and 0.2 V lower in overpotential. Calculations show that surface defects due to Fe leaching contribute significantly to decrease the overpotential.

Fluoxetine-enhanced autophagy ameliorates early brain injury via inhibition of NLRP3 inflammasome activation following subrachnoid hemorrhage in rats.

BACKGROUND: The NLRP3 inflammasome is a multiprotein complex that regulates the innate immune inflammatory response by activating caspase-1 and subsequent IL-1ß and IL-18. Fluoxetine has been shown to have the anti-inflammatory properties in many disease models. However, the effects and mechanisms of these effects of fluoxetine in early brain injury after subarachnoid hemorrhage (SAH) have not been defined. METHODS: The SAH model was induced by an endovascular perforation in adult male Sprague-Dawley (SD) rats weighing 300-320 g. N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (AC-YVAD-CMK) was injected intraperitoneally (5 mg/kg) 1 h after SAH. Fluoxetine was administered via intravenous route 6 h after SAH. 3-Methyladenine (3-MA) was intracerebroventricularly injected 20 min before SAH. SAH grade, neurological function, brain water content, propidium iodide (PI) staining, western blot, double immunostaining, and transmission electron microscopy were performed. RESULTS: Expression of caspase-1 increased and peaked at 24 h after SAH. Caspase activation was along with the increased necrotic cells, which occurred mainly in neurons. Necrotic cell death of microglia and astrocyte were also found. Administration of AC-YVAD-CMK, a caspase-1 inhibitor, reduced the expression of IL-1ß and IL-18 and the number of PI-positive cells, attenuated brain edema, and improved neurological function, which was also observed in fluoxetine-treated rats. Furthermore, fluoxetine treatment significantly decreased the expression of NLRP3 and cleaved caspase-1 and upregulated the expression of beclin-1, a marker for autophagy. Finally, the effects of fluoxetine in NLRP3 inflammasome activation were reversed by additional 3-MA administration. CONCLUSIONS: Together, our present study indicated that NLRP3 inflammasome and caspase-1 activation play a deleterious role in early brain injury and fluoxetine mitigates NLRP3 inflammasome and caspase-1 activation through autophagy activation after SAH, providing a potential therapeutic agent for SAH treatment.

Methylene blue attenuates neuroinflammation after subarachnoid hemorrhage in rats through the Akt/GSK-3ß/MEF2D signaling pathway.

Subarachnoid hemorrhage (SAH) is a serious medical problem with few effective pharmacotherapies available, and neuroinflammation has been identified as an important pathological process in early brain injury (EBI) after SAH. Methylene blue (MB) is an older drug that has been recently proven to exert extraordinary neuroprotective effects in several brain insults. However, no study has reported the beneficial effects of MB in SAH. In the current investigation, we studied the neuroprotective effects of MB in EBI after SAH and focused on its anti-inflammatory role. A total of 303 rats were subjected to an endovascular perforation process to produce an SAH model. We found that MB could significantly ameliorate brain edema secondary to BBB disruption and alleviate neurological dysfunction after SAH. MB administration also promoted the phosphorylation of Akt and GSK-3ß, leading to an increased concentration of MEF2D in the nucleus. The cytokine IL-10 was up-regulated, and IL-1ß, IL-6 and TNF-α were down-regulated after MB administration. MB administration could also alleviate neutrophil infiltration and microglia activation after SAH. MK2206, a selective inhibitor of Akt, abolished the neuroprotective effects of MB, inhibited the phosphorylation of Akt and prevented the nuclear localization of MEF2D. MK2206 also reduced the expression of IL-10 and increased the expression of pro-inflammatory cytokines. In conclusion, these data suggested that MB could ameliorate neuroinflammatory responses after SAH, and its anti-inflammatory effects might be exerted via activation of the Akt/GSK-3ß/MEF2D pathway.

Characterization and Potential Antitumor Activity of Polysaccharide from Gracilariopsis lemaneiformis.

Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL is detrimental to tumors, we purified PGL to characterize its chemical composition, molecular weight, and sugar and protein content and investigated its antitumor activity. We demonstrated that PGL exerted its antitumor activities by modulating cell viability, morphology, apoptosis, and the apoptosis-related Fas/FasL signaling pathway in the human lung cancer cell line A549, the gastric cancer cell line MKN28, and the mouse melanoma cell line B16. Our data provide the first evidence that PGL inhibits cell proliferation by inducing apoptosis, which is largely mediated by Fas/FasL in cancer cells, suggesting that PGL might be a novel therapeutic agent against cancer.

The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention.

Traumatic brain injury (TBI) is a serious medical and social problem worldwide. Because of the complex pathophysiological mechanisms of TBI, effective pharmacotherapy is still lacking. The microglial cells are resident tissue macrophages located in the brain and have two major polarization states, M1 phenotype and M2 phenotype, when activated. The M1 phenotype is related to the release of proinflammatory cytokines and secondary brain injury, while the M2 phenotype has been proved to be responsible for the release of anti-inflammation cytokines and for central nervous system (CNS) repair. In animal models, pharmacological strategies inhibiting the M1 phenotype and promoting the M2 phenotype of microglial cells could alleviate cerebral damage and improve neurological function recovery after TBI. In this review, we aimed to summarize the current knowledge about the pathological significance of microglial M1/M2 polarization in the pathophysiology of TBI. In addition, we reviewed several drugs that have provided neuroprotective effects against brain injury following TBI by altering the polarization states of the microglia. We emphasized that future investigation of the regulation mechanisms of microglial M1/M2 polarization in TBI is anticipated, which could contribute to the development of new targets of pharmacological intervention in TBI.

Study of CuSb bimetallic flow-through gas diffusion electrodes for efficient electrochemical CO2 reduction to CO.

Electrochemical CO2 reduction (eCO2R) to industrially important feedstock has received great attention, but it faces different challenges. Among them, the poor CO2 mass transport due to low intrinsic CO2 solubility significantly limits the rate of reduction reactions, leading to lower catalytic performance; thereby, commercially relevant current densities can't be achieved. Moreover, the poor activity and selectivity of high-cost monometallic catalysts, including Cu, Zn, Ag, and Au, undermine the efficiency of eCO2R. Flow-through gas diffusion electrodes (FTGDE), a newly developed class of GDEs, can potentially solve the issue of poor CO2 mass transport because they directly feed the CO2 to the catalyst layer. In addition, abundant surface area, porous structure, and improved triple-phase interface make them an excellent candidate for extremely high rate eCO2R. Antimony, a low-cost and abundant metalloid, can be effectively tuned with Cu to produce useful products such as CO, formate, and C2H4 through eCO2R. Herein, a series of porous binary CuSb FTGDEs with different Sb compositions are fabricated for the electrocatalytic reduction of CO2 to CO. The results show that the catalytic performance of CuSb FTGDEs improved with increasing Sb content up to a certain threshold, beyond which it started to decrease. The CuSb FTGDE with 5.4 g of antimony demonstrated higher current density (206.4 mA/cm2) and faradaic efficiency (72.82 %) at relatively lower overpotentials. Compared to gas diffusion configuration, the poor catalytic activity and selectivity achieved by CuSb FTGDE in non-gas diffusion configuration signifies the importance of improved local CO2 concentration and improved triple-phase interface formation in GDE configuration. The several hours stable operation of CuSb FTGDEs during eCO2R demonstrates its potential for efficient electrocatalytic conversion applications.