A minimalist cancer cell membrane-shielded biomimetic nanoparticle for nasopharyngeal carcinoma active-targeting therapy.

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.

Identification of MATE Family and Characterization of GmMATE13 and GmMATE75 in Soybean's Response to Aluminum Stress.

The multidrug and toxic compound extrusion (MATE) proteins are coding by a secondary transporter gene family, and have been identified to participate in the modulation of organic acid exudation for aluminum (Al) resistance. The soybean variety Glycine max "Tamba" (TBS) exhibits high Al tolerance. The expression patterns of MATE genes in response to Al stress in TBS and their specific functions in the context of Al stress remain elusive. In this study, 124 MATE genes were identified from the soybean genome. The RNA-Seq results revealed significant upregulation of GmMATE13 and GmMATE75 in TBS upon exposure to high-dose Al3+ treatment and both genes demonstrated sequence homology to citrate transporters of other plants. Subcellular localization showed that both proteins were located in the cell membrane. Transgenic complementation experiments of Arabidopsis mutants, atmate, with GmMATE13 or GmMATE75 genes enhanced the Al tolerance of the plant due to citrate secretion. Taken together, this study identified GmMATE13 and GmMATE75 as citrate transporter genes in TBS, which could improve citrate secretion and enhance Al tolerance. Our findings provide genetic resources for the development of plant varieties that are resistant to Al toxicity.

Predictors of physical inactivity among pregnant women.

It is recommended that pregnant women be physically active to promote maternal and child health. This study aimed to explore the prevalence of physical inactivity and its modifiable predictors in the three trimesters in Chinese pregnant women. Four hundred forty-four pregnant women completed the Pregnant Physical Activity Questionnaire in the first, second, and third trimesters. The prevalence of physical inactivity reached its highest (66.2%) in the first trimester and lowest (19.4%) in the second trimester. Pregnant women with inadequate physical activity knowledge and low self-efficacy were at higher risk for physical inactivity. Monitoring physical inactivity could be incorporated into antenatal care and start from the first trimester. Prenatal care professionals should take action to increase pregnant women's physical activity self-efficacy and knowledge to enhance their physical activity.

Predictors of anxiety among pregnant women with gestational diabetes mellitus and their partners: The mediating role of marital satisfaction.

AIMS: This study aims to examine the prevalence of anxiety symptoms and identify predictors of anxiety among pregnant women with gestational diabetes mellitus and their partners and explore the mediating role of marital satisfaction between maternal and paternal anxiety. DESIGN: A cross-sectional study was conducted in Guangzhou, China, from July 2021 to May 2022. METHODS: A total of 306 dyads of pregnant women with gestational diabetes mellitus and their partners completed the State-Trait Anxiety Inventory, Locke-Wallace Marital Adjustment Test and the socio-demographic and clinical data sheet. RESULTS: The prevalence of anxiety symptoms was 32.4% and 36.6% in pregnant women with gestational diabetes mellitus and their partners, respectively. The predictors of maternal anxiety were paternal anxiety, maternal marital satisfaction, maternal monthly salary, fasting glucose value and 1-h glucose value. By contrast, the predictors of paternal anxiety were maternal anxiety, paternal marital satisfaction and paternal monthly salary. Moreover, the relationship between maternal and paternal anxiety was mediated by marital satisfaction. CONCLUSIONS: The anxiety symptoms of pregnant women with gestational diabetes mellitus and their partners influence each other, and this relationship was mediated by marital satisfaction. Every couple should be screened for anxiety symptoms and treated as a team rather than focusing solely on the pregnant woman.

The Mediating Role of Physical Activity Self-Efficacy in Predicting Moderate-Intensity Physical Activity in Pregnant People at High Risk for Gestational Diabetes.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common medical complication in pregnancy. Moderate-intensity physical activity during pregnancy can lower the risk of GDM. However, the relationship between moderate-intensity physical activity and correlated factors among pregnant people at high risk for GDM remains unknown. METHODS: A cross-sectional study was conducted in China. Two hundred fifty-two participants completed the Pregnancy Physical Activity Questionnaire, Pregnancy Physical Activity Self-Efficacy Scale, Physical Activity Knowledge Questionnaire, Physical Activity Social Support Scale, 7-item Generalized Anxiety Disorder Scale, Edinburgh Postnatal Depression Scale, and a sociodemographic data sheet. Structural equation modeling was used to explore the direct and indirect associations between the study variables. RESULTS: A total of 51.6% of the participants did not meet the current physical activity guidelines. Only physical activity self-efficacy was significantly correlated with moderate-intensity physical activity. Physical activity self-efficacy mediated the relationship between moderate-intensity physical activity and knowledge of physical activity, social support for physical activity, and anxiety symptoms. Furthermore, knowledge of physical activity was also associated with improved moderate-intensity physical activity mediated by reduced anxiety symptoms and increased physical activity self-efficacy. CONCLUSION: Our study revealed a high prevalence of not meeting current physical activity guidelines among pregnant people at high risk for GDM. Physical activity self-efficacy played an important mediating role in predicting moderate-intensity physical activity. Future studies should focus on enhancing self-efficacy to improve moderate-intensity physical activity for pregnant people at high risk for GDM.

Social Support, Parenting Self-Efficacy, and Postpartum Depression Among Chinese Parents: The Actor-Partner Interdependence Mediation Model.

INTRODUCTION: Postpartum depression affects both mothers and fathers. This study aimed to examine the relationships between social support, parenting self-efficacy, and postpartum depression in Chinese mothers and fathers and assess the mediating effect of parenting self-efficacy using a dyadic perspective. METHODS: A cross-sectional study was implemented from December 2020 to July 2021 in Guangzhou, China, with 309 pairs of parents. The Edinburgh Postnatal Depression Scale, Social Support Rating Scale, Parenting Sense of Competence Scale-Efficacy subscale, and sociodemographic data sheet were completed by both parents. Dyadic analysis was conducted using the actor-partner interdependence mediation model. An actor effect is the relationship between variables within an individual, whereas a partner effect is the relationship between variables in the individual and the dyadic partner. RESULTS: In total, 20.7% of mothers and 11.7% of fathers had elevated postpartum depressive symptoms at 6 weeks postpartum. The model revealed 6 actor effects: social support was positively associated with parenting self-efficacy for mothers (ß, 0.39; 95% CI, 0.28-0.49) and fathers (ß, 0.39; 95% CI, 0.30-0.48) and negatively associated with postpartum depression for mothers (ß, -0.22; 95% CI, -0.32 to -0.12) and fathers (ß, -0.37; 95% CI, -0.48 to -0.26). Parenting self-efficacy was negatively associated with postpartum depression in mothers (ß, -0.41; 95% CI, -0.53 to -0.29) and fathers (ß, -0.24; 95% CI, -0.37 to -0.12). Maternal social support had a partner effect on paternal parenting self-efficacy (ß, 0.14; 95% CI, 0.04-0.24). Parenting self-efficacy mediated between social support and postpartum depression for both parents (mothers: ß, -0.16; 95% CI, -0.23 to -0.10; fathers: ß, -0.10; 95% CI, -0.16 to -0.05). DISCUSSION: Postpartum depression was a dyadic phenomenon. Increasing mother-centered social support has the potential to improve the parenting self-efficacy of both parents and reduce the likelihood of postpartum depression.

The formate dehydrogenase enhances aluminum tolerance of tobacco.

The formate dehydrogenase (FDH) is regarded as a universal stress protein involved in various plant abiotic stress responses. This study aims to ascertain GmFDH function in conferring tolerance to aluminum (Al) stress. The bioinformatics analysis demonstrates that GmFDH from Tamba black soybean (TBS) encodes FDH. Quantitative reverse transcription-PCR (qRT-PCR) showed that GmFDH expression was induced by Al stress with a concentration-time-specific pattern. Moreover, Al stress promotes formate content and activates FDH activity. Further studies revealed that GmFDH overexpression alleviated root growth of tobacco under Al stress inhibition and reduced Al and ROS accumulation in roots. In addition, transgenic tobacco had much more root citrate exudation and much higher activity of antioxidant enzymes than wild type. Moreover, under Al stress, NtMATE and NtALS3 expression showed no changes in wild type and overexpression lines, suggesting that here the known Al-resistant mechanisms are not involved. However citrate synthase activity is higher in transgenic tobaccos than that of wild type, which might be the reason for citrate secretion increase. Thus, the increased Al tolerance of GmFDH overexpression lines is likely attributable to enhanced activities of antioxidant enzymes and promoting citrate secretion. Taken together, our findings advance understanding of higher plant Al toxicity mechanisms and suggest a possible new route towards the improvement of plant growth under Al stress.

Association of remnant cholesterol with intracranial atherosclerosis in community-based population: The ARIC study.

OBJECTIVE: To evaluate the association between remnant cholesterol (remnant-C) and intracranial atherosclerotic disease (ICAD) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: We studied 1,564 participants with data on lipid profiles and high-resolution vessel wall MRI (VWMRI) from the ARIC-NCS. Remnant-C was computed as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C). The primary outcomes were the presence of intracranial plaques and luminal stenosis. Contributors were separated into four different groups based on remnant-C (22 mg/dL) and LDL-C (100 mg/dL) levels to investigate the function of remnant-C vs. LDL-C on ICAD. Multivariable logistic regression models were utilized to estimate the correlation among the discordant/concordant remnant-C and LDL-C, and ICAD. RESULTS: A total of 1,564 participants were included (age 76.2 ± 5.3). After multivariable adjustment, log remnant-C was correlated with greater ICAD risk [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.01 to 1.83]. The lower remnant-C/higher LDL-C group and the higher remnant-C/lower LDL-C group manifested a 1.53-fold (95% CI 1.06 to 2.20) and 1.52-fold (95% CI 1.08 to 2.14) greater risk of ICAD, relative to those having lower remnant-C/low LDL-C. Additionally, remnant-C ≥ 22 mg/dL distinguished participants at a greater risk of the presence of any stenosis compared to those at lower levels, even in participants with optimal levels of LDL-C. CONCLUSIONS: Elevated levels of remnant-C were connected to ICAD independent of LDL-C and traditional risk factors. The mechanisms of remnant-C association with ICAD probably offer insight into preventive risk-factor of ischemic stroke.

Clinical practice guidelines on physical activity and exercise for pregnant women with gestational diabetes mellitus: A systematic review.

AIM: This review aimed to appraise clinical guidelines about exercise for women with gestational diabetes mellitus and summarize consensus and inconsistent recommendations. BACKGROUND: Exercise is an effective non-pharmacological therapeutic for gestational diabetes mellitus, but the variety of relevant clinical practice guidelines is confusing for healthcare professionals. DESIGN: This is a systematic review of clinical practice guidelines. DATA SOURCES: Websites of guideline development institutions, eight literature databases and organizations of obstetricians, gynaecologists, midwives, and medical sports associations were searched for guidelines published from January 2011 to October 2021. REVIEW METHODS: Two reviewers independently extracted recommendations. Four reviewers assessed guideline quality using the AGREE II instrument independently. RESULTS: Fifteen guidelines were included. All women with diabetes are recommended to exercise during pregnancy. The consistent recommendations were for pre-exercise screening, for 30 min per exercise session on 5 days of the week or every day after meals, exercise at moderate intensity, using aerobic and resistance exercise, and walking. The main non-consistent recommendations included warning signs for women on insulin during exercise, minimum duration per session, intensity assessment, duration and frequency of sessions for strengthening and flexibility exercise and detailed physical activity giving birth. CONCLUSIONS: Guidelines strongly support pregnant women with diabetes to exercise regularly. Research is needed to make non-consistent recommendations clear.

Association between Serum Amyloid A Level and White Matter Hyperintensity Burden: a Cross-Sectional Analysis in Patients with Acute Ischemic Stroke.

INTRODUCTION: This work aimed to determine the potential link between white matter hyperintensity (WMH) burden and serum amyloid A (SAA) level in patients with acute ischemic stroke. METHODS: Consecutive patients with acute large artery atherosclerosis (LAA) stroke between April 2021 and May 2022 were included. WMH volumes (periventricular, deep, and total) were measured using the Fazekas score and a semiautomated volumetric analysis on fluid-attenuated inversion recovery-magnetic resonance imaging. The burdens of WMH were scored to assess the dose-dependent association between SAA and WMH volume. Multivariate regression and a two-piecewise linear regression model were used to evaluate whether SAA levels are an independent predictor of WMH, and to discover the threshold effect or saturation effect of SAA levels with respect to WMH volume. RESULTS: The mean age of patients was 63.2 ± 11.5 years, with 65.9% men. The median SAA level was 3.93 mg/L and the total WMH volume of 6.86 cm3. In the multivariable analysis, SAA remained an independent predictor of total WMH volume [ß = 0.82, 95% confidence interval (CI) = 0.49-1.07, p < 0.001], periventricular WMH volume (adjusted ß = 0.76, 95% CI = 0.46-1.07, p < 0.001), and deep WMH volume (adjusted ß = 0.26, 95% CI = 0.06-0.45, p = 0.011) after controlling for confounders. Furthermore, SAA levels were associated with periventricular Fazekas score, deep Fazekas score, and Fazekas grades. Threshold effect and saturation effect analyses demonstrated a nonlinear relationship between SAA levels and periventricular white matter hyperintensity (PVWMH) volumes, with SAA levels (2.12-19.89 mg/L) having significant dose-dependent relationships with periventricular WMH volumes (adjusted ß = 1.98, 95% CI = 1.12-2.84, p < 0.001). CONCLUSION: SAA level ranging from 2.12 to 19.89 mg/L is dose-dependently associated with periventricular WMH development. These findings point the way forward for future research into the pathophysiology of WMH.

Predictors of physical activity among Chinese pregnant women during the first trimester: A cross-sectional study.

Physical activity during pregnancy has numerous health benefits for the woman and the foetus. The current study investigated physical activity engagement and its predictors among pregnant Chinese women during the first trimester. A total of 687 pregnant women completed the Pregnancy Physical Activity Questionnaire. Bivariate and multivariate logistic regression were used to analyse the data. The current physical activity guidelines were not met by 64.3% of respondents. Women with higher levels of physical activity self-efficacy (aOR = 0.96; 95% CI: 0.92-0.99) and social support (aOR = 0.95; 95% CI: 0.94-0.97) had lower odds of not meeting the current physical activity guidelines. Women who were aged < 35 years (aOR = 1.85; 95% CI: 1.02-3.34), had lower education (aOR = 1.63; 95% CI: 1.04-2.55), were primiparous (aOR = 11.03; 95% CI: 6.98-17.44), were unsure of their delivery mode (aOR = 2.32; 95% CI: 1.95-5.64), and those who had higher levels of pregnancy-associated discomfort (aOR = 1.10; 95% CI: 1.03-1.19) had higher odds of not meeting the current physical activity guidelines. The current study suggests that healthcare professionals should assess physical activity engagement during routine antenatal care and increase efforts to strengthen pregnant women's self-efficacy and social support to promote physical activity engagement during the first trimester.

Perceived stress, marital satisfaction, and prenatal depression among couples with gestational diabetes mellitus.

OBJECTIVE: This study aimed to explore the prevalence of prenatal depression and to determine the dyadic relationship between perceived stress, marital satisfaction, and prenatal depression in pregnant women with gestational diabetes mellitus (GDM) and their partners. BACKGROUND: GDM during pregnancy is a very stressful event for couples. However, previous studies have largely focused on pregnant women, with few including their partners. METHODS: A cross-sectional study was conducted in Guangzhou, China, from 30 July to 2 December 2021. Three hundred fourteen couples with GDM completed the Perceived Stress Scale, Locke-Wallace Marital Adjustment Scale, and Edinburgh Postnatal Depression Scale. Dyadic analysis was conducted using the actor-partner interdependence mediation model. RESULTS: The prevalence of depressive symptoms was 13.4% in pregnant women with GDM and 8.3% in their partners. Regarding the actor effects, perceived stress was positively associated with prenatal depression in pregnant women with GDM and their partners, respectively, and marital satisfaction acted as a mediating role. Regarding the partner effects, paternal perceived stress was negatively associated with maternal marital satisfaction, and maternal marital satisfaction mediated the association between paternal perceived stress and maternal prenatal depression. CONCLUSIONS: Dyadic effects of perceived stress, marital satisfaction, and prenatal depression exist in couples with GDM.

Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice.

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (n = 80) and RNA expression microarray data (n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size (n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 (n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.

Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke.

In order to explore the epigenetic characteristics of hemorrhagic transformation (HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), circular RNA (circRNA) and mircoRNA (miRNA) between the two groups. To further explore the role of differentially expressed genes in HT, we annotated the function of differentially expressed genes by using gene ontology (GO) and pathway analysis on the results and showed that there were 1,051 differential expressions of lncRNAs, 2,575 differential expressions of mRNAs, 447 differential expressions of circRNAs and 47 miRNAs in patients with HT compared with non-HT patients. Pathway analysis showed that ubiquitin-mediated proteolysis, MAPK signal pathway, axon guidance, HIF-1 signal pathway, NOD-like receptor signal pathway, beta-alanine metabolism, Wnt signal pathway, sphingolipid signal pathway, neuroactive ligand-receptor interaction, and intestinal immune network used in IgA production play an important role in HT. Terms such as iron homeostasis, defense response, immune system process, DNA conformational change, production of transforming growth factor beta-2, and oxidoreductase activity were enriched in the gene list, suggesting a potential correlation with HT. A total of 261 lncRNA-miRNA relationship pairs and 21 circRNA-miRNA relationship pairs were obtained; additionally, 5 circRNAs and 13 lncRNAs were screened, which can be used as competing endogenous RNA (ceRNA) to compete with miRNA in the co-expression network. Co-expression network analysis shows that these differentially expressed circRNA and lncRNA may play a vital role in HT and provide valuable information for new biomarkers or therapeutic targets.

Clinical Practice Guidelines That Address Physical Activity and Exercise During Pregnancy: A Systematic Review.

INTRODUCTION: Physical activity is recommended for healthy pregnant women. Clinical practice guidelines vary with regard to initial time, duration, or type of physical activity that is recommended, which is confusing for health care professionals and pregnant women alike. This study aimed to appraise clinical guidelines relevant to physical activity for pregnant women and summarize consensus and discrepant recommendations. METHODS: The websites of organizations that develop guidelines including those of obstetricians, gynecologists, midwives, and medical sports associations were searched in addition to 9 literature databases for the period from January 2010 through November 2020. Guidelines were included if they were published in a journal or on a website in English or Chinese; were labeled as a recommendation guideline, position paper, practice parameter, or consensus statement; and addressed physical activity for pregnant women. Two authors independently extracted recommendations. Four reviewers independently assessed guideline quality using the AGREE II instrument. RESULTS: Thirteen guidelines met the inclusion criteria. The guidelines developed by the World Health Organization and the National Institute for Health and Clinical Excellence were deemed to have the highest methodological quality. The recommendations were consistent with regard to recommended exercise duration, frequency, intensity, and type of physical activity. The main discrepant recommendations included best tools for conducting pre-exercise screening and assessing intensity of exertion. Guidelines also differ on optimal heart rate during exercise, when in pregnancy to initiate an exercise regimen, and duration or frequency of strengthening exercises. DISCUSSION: Of the 13 guidelines, 2 were found to have good methodological quality. The recommendations that were consistent across the differing guidelines can support health care providers in counseling women about physical activity during pregnancy. The recommendations that are discrepant among these guidelines may contribute to confusion and a reluctance to recommend exercise during pregnancy. Research is needed to clarify discrepant recommendations.

Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice.

Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice.

Separation and characterization of phenylamides from Piper kadsura using preparative supercritical fluid chromatography and ultra-high-performance supercritical fluid chromatography-tandem mass spectrometry.

A preparative supercritical fluid chromatography method for the separation of Piper kadsura obtained five phenylamide compounds, which had the same structural skeleton, but changed in the number and position of methoxyl substituents. To improve the separation selectivity of these structural analogues, silica, phenyl, and chiral stationary phases were screened. Only through the combination of Chiral C and phenyl columns could the separation of the five phenylamides be solved. The two-step strategy using preparative supercritical fluid chromatography presented good orthogonality that ensured the purity of the phenylamides. Then, an ultra-high-performance supercritical fluid chromatography hyphened tandem mass spectrometry method was developed, and the fragmentation pattern of phenylamides was summarized. It mainly cleaved in the amide bond to produce the fragment ion, which could help to judge the substituent positions. Twenty-eight possible molecular weights of hydroxyl and methoxyl substituted phenylamides were calculated and screened. Nine compounds were extracted in three [M + H]+ ions at m/z 284.13, 314.13, and 344.13, including five purified compounds and the other four positional or trans-cis phenylamide isomers in low content. The methods developed in this research were useful in the separation and characterization of phenylamide analogues.

Glucose Metabolic Dysfunction in Neurodegenerative Diseases-New Mechanistic Insights and the Potential of Hypoxia as a Prospective Therapy Targeting Metabolic Reprogramming.

Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.

Metabolic Reprogramming: Strategy for Ischemic Stroke Treatment by Ischemic Preconditioning.

Stroke is one of the leading causes of death and permanent disability worldwide. Ischemic preconditioning (IPC) is an endogenous protective strategy, which has been reported to exhibit a significant neuroprotective effect in reducing the incidence of ischemic stroke. However, the underlying neuroprotective mechanisms of IPC remain elusive. An increased understanding of the pathogenic mechanisms of stroke and IPC serves to highlight the importance of metabolic reprogramming. In this review, we summarize the metabolic disorder and metabolic plasticity in the incidence and progression of ischemic stroke. We also elaborate how IPC fully mobilizes the metabolic reprogramming to maintain brain metabolic homeostasis, especially for energy and redox homeostasis, and finally protects brain function in the event of an ischemic stroke.