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• Hypertension and smoking are positively associated with an increased risk of ischemic stroke in Ph-negative MPNs patients. • Hypertension was the only independent risk factor for ischemic stroke in Ph-negative MPNs, regardless of JAK2V617F mutation. • It's crucial to assess the role of neutrophil/lymphocyte percentages as additional risk factors identified in our study. Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) are linked with various complications, notably ischemic stroke. The study aims to identify risk factors for ischemic stroke in Ph-negative MPNs patients. Patients were categorized into two groups based on whether they had experienced ischemic stroke. Subsequently, an analysis of demographics, biochemical makers, and genetic mutations (JAK2V617F and CALR mutations), was conducted to identify potential associations with an elevated risk of ischemic stroke in individuals with Ph-negative MPNs. A total of 185 patients diagnosed with Ph-negative MPNs participated in the study, including 82 with essential thrombocythemia (ET), 78 with polycythemia vera (PV), and 25 with primary myelofibrosis (PMF). Among these, 57 patients (30.8 %) had a history of ischemic stroke. Independent risk factors associated with ischemic stroke in Ph-negative MPNs patients included hypertension (OR = 5.076) and smoking (OR = 5.426). Among ET patients, smoking (OR = 4.114) and an elevated percentage of neutrophils (OR = 1.080) were both positively correlated with ischemic stroke incidence. For PV patients, hypertension (OR = 4.647), smoking (OR = 6.065), and an increased percentage of lymphocytes (OR = 1.039) were independently associated with ischemic stroke. Regardless of the presence of the JAK2V617F mutation, hypertension was the sole positively and independently associated risk factor for ischemic stroke. The odds ratios for patients with the JAK2V617F mutation was 3.103, while for those without the mutation, it was 11.25. Hypertension was a more substantial factor associated with an increased incidence of ischemic stroke in Ph-negative MPNs patients. [ABSTRACT FROM AUTHOR]

The rheological, thermal and textural properties of batter are critical for the eating and processing quality of soft cake products. Wheat starch molecular structures play an important role on these properties. However, the underlying mechanisms are not well understood. In this study, fluorophore-assisted carbohydrate electrophoresis and size-exclusion chromatography were used to measure amylopectin and amylose chain-length distribution. The obtained data were fitted with two different biosynthesis-based models, resulting in few biologically-meaningful parameters. For cake batter, the rheological, thermal and textural properties were measured by rheometer, differential scanning calorimetry and texture analyser. The length of amylose intermediate to long chains and amylopectin long chains was significantly positively correlated with the viscoelasticity of cake batter. The length of long amylose chains showed a negative correlation with the frequency value of crossover point between G′ and G″ curves. Moreover, different combinations of long amylopectin and intermediate-long amylose chains contributed to the formation of multi-endothermic gelatinization peaks. From flour-water system to flour-lipid-protein system, the main factors determining rheological and thermal properties changed from short amylopectin to long amylopectin and intermediate-long amylose chains. This study provides the first associations between starch molecular fine structure and functional properties of cake batter, which could help food industry breed and select suitable wheat varieties for improved batter quality. [Display omitted] • The functional properties of flour-lipid cake batter were investigated in this study. • Long AP & medium and long AM chains are positively correlated with viscoelasticity. • Decrease of long AM chain length increases crossover point x value of rheology curves. • Cake batter shows two endothermic peaks in gelatinization curves. • Chain length distribution of AM is the determining factor for flour-lipid batter. [ABSTRACT FROM AUTHOR]

Aims In this study, we investigated the effects of Bax-inhibiting peptide (Bip)-V5, an anti-apoptosis membrane-permeable peptide, on the 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model rats. Materials and methods Rats were randomly divided into five groups: Control, 6-OHDA only, Vehicle + 6-OHDA, zVAD + 6-OHDA, and V5 + 6-OHDA, that rats were preadministrated with different reagents before 6-OHDA administration. Key findings The result showed that intrastriatal preadministration of Bip-V5 significantly decreased the amphetamine-induced rotation of the 6-OHDA model rats and the loss of the nigral dopaminergic (DA) neurons. Moreover, Bip-V5 intrastriatal preadministration not only significantly decreased the expression of activated caspase 9 and activated caspase 3 but also decreased the enhanced expression of AIF and its nuclear translocation in the SNpc. The results in our study provide the first experimental evidence that both caspase-dependent and AIF-dependent apoptosis pathways are involved in the loss of the nigral DA neurons caused by intrastriatal administration of 6-OHDA, and intrastriatal preadministration of Bip-V5 can inhibit the above two apoptosis pathways to protect the nigral DA neurons. Significance Our results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the combination effects of bone marrow stromal cells (BMSCs) and oxiracetam for ischemic stroke. Forty Sprague Dawley female rats (220 ± 20 g) were subjected to a 2-hour ischemic middle cerebral artery occlusion (MCAO)-24 hours reperfusion model. The rats were randomly divided into 4 groups. Rats from BMSCs group, oxiracetam group, and BMSCs + oxiracetam group accepted injection of BMSCs (3 × 10(6) cells), oxiracetam (800 mg/kg), and BMSCs + oxiracetam, respectively. Rats from control group did not receive any interventions after ischemia reperfusion. The neurologic function was examined by modified neurological severity scores (mNSS). B-cell lymphoma 2 (Bcl-2) expression and apoptosis were detected by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The mNSS was decreased in all treatment groups and that in BMSCs + oxiracetam group was lower than BMSCs group and oxiracetam group (P < .05). The expression of Bcl-2 was unregulated in all treatment groups (P < .05), and similarly, the expression of Bcl-2 in BMSCs + oxiracetam group was higher than BMSCs group and oxiracetam group (P < .05). Control group displayed more TUNEL-positive cells than the treatment groups, and BMSCs + oxiracetam group displayed less apoptotic cells than BMSCs group or oxiracetam group (P < .05). Transplantation of BMSCs can promote the recovery of neurologic function in MCAO rats, and the effect of BMSCs combined with oxiracetam was better than the either one. Upregulation of Bcl-2 resulting in a decrease of apoptosis may be one of the mechanisms of BMSCs treatment for cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]

Abstract: In order to measure the relationship between economic activities and energy consumption for low-carbon economy strategy in ethnic minority autonomous regions, this paper used the Carbon Footprint Model and based the VAR model, used the Impulse Response Function method to describe the dynamic relations between economic growth and the energy Carbon Footprint in these regions. The result indicated that there is a strong interactive response between economic growth and Energy Carbon Footprint. The increases of Carbon Footprint can also cause the increase of GDP, this means the economic growth will be growth more rapidly depends on the massive energy consumption in the short-term, but when the economic growth to the certain extent, energy''s excessive consumption can’t bring higher growth of economic, even give the negative influence to the economic growth, therefore, transforming economic growth pattern, modifying industrial structure and improving energy efficiency are useful ways for low-carbon economy. [Copyright &y& Elsevier]

The pathogenesis of systemic lupus erythematosus (SLE) is incompletely understood. Studies in both lupus animal models and human disease indicate a clear role for epigenetic defects, particularly DNA methylation, in the pathogenesis of lupus. T-cell DNA from active lupus patients is hypomethylated, which results in overexpression of methylation-regulated genes, T-cell autoreactivity, and autoimmunity in vivo. Inducing an extracellular signal-regulated kinase (ERK) signaling defect in T cells using a transgenic mouse model resulted in reduced DNA methyltransferase 1 (DNMT1) expression, overexpression of methylation-sensitive genes, and anti-double-stranded DNA (anti-dsDNA) antibody production. ERK signaling is known to be defective in lupus T cells, and this defect is now explained by impaired T-cell protein kinase C (PKC) delta activation. Herein, we discuss how defective epigenetic regulation is involved in the pathogenesis of lupus, which includes both DNA methylation and histone modification changes. [Copyright &y& Elsevier]

A novel second generation retroviral producer cell strategy (an adenoviral/retroviral combined delivery system) has been developed by this laboratory. In the present studies, this delivery system was used to examine its delivery efficiency in vitro and in vivo by using a marker gene, LacZ, and a therapeutic gene, herpes simplex virus thymidine kinase (HSV-tk), both of which were transduced into a tumor cell line KBALB. In the in vitro experiments for delivery efficacy of the LacZ gene, the delivery efficiency of KBALB+KBALBLNPOZAdN/H (1:1) was 27.8% higher than that of KBALB+KBALBLNPOZ (1:1) (P<0.01). For the antitumor effect of HSV-tk/ganciclovir (GCV), the death ratio of KBALB+KBALBLNCTKAdN/H (1:1) was higher than that of KBALB+KBALBLNCTK (1:1), on 4, 6, and 8 days at a concentration of 0.1, 1, and 10 μg/ml, respectively (P<0.01 or P<0.05). In the in vivo experiments for LacZ gene expression, the delivery efficiency in KBALB+KBALBLNPOZAdN/H (1:1) was 21.5% more efficient than that in KBALB+KBALBLNPOZ (1:1) (P<0.01). For HSV-tk/GCV antitumor effect, the suppression of tumors by KBALB+KBALBLNCTKAdN/H (1:1) was more effective than that by KBALB+KBALBLNCTK (1:1) (P<0.05). Results suggest that this new delivery system is more efficient than the traditional in vitro and in vivo retroviral vector delivery system. [Copyright &y& Elsevier]

PTBP1KD-BMSCs can reduce the cerebral infarction volume, neurological function score, and improve neuronal damage in rats with ischemia–reperfusion, which is attributed to the down-regulation of PTBP1 , which inhibits the proliferation of BMSCs, slows down cell aging, and enhances cell viability. PTBP1KD-BMSCs may play a protective role in regulating ferroptosis by inhibiting the JNK/P38 pathway to increase the antioxidant activity and inhibit lipid peroxidation in neurons with ischemia–reperfusion injury. [Display omitted] • PTBP1KD-BMSCs treat ischemia–reperfusion injury in neurons. • PTBP1 regulates the BMSC cell cycle and increases cell viability. • PTBP1KD-BMSCs conditioned medium protects PC12 cells from OGD/R. • It inhibits ferroptosis and regulates the P38/JNK pathway in PC12 cells. Over the years, the neuroprotective potential of bone marrow mesenchymal stem cells (BMSCs) in acute ischemic stroke has attracted significant attention. However, BMSCs face challenges like short metabolic cycles and low survival rates post-transplant. Polypyrimidine tract-binding protein 1 (PTBP1) is an immunomodulatory RNA-binding protein that regulates the cell cycle and increases cell viability. This study investigated the protective effects and underlying mechanism of PTBP1 knockdown in BMSCs (PTBP1KD-BMSCs) following ischemia–reperfusion injury (IRI) in neurons. BMSCs were isolated from Sprague-Dawley rat femurs and characterized through flow cytometry and differentiation induction. PTBP1 knockdown inhibited BMSCs proliferation. Co-culture with PTBP1KD-BMSCs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, while increasing glutathione (GSH) production in oxygen and glucose deprivation/reperfusion-induced PC12 cells. Transcriptome sequencing analysis of PC12 cells suggested that the protective effect of PTBP1KD-BMSCs against injury may involve ferroptosis. Furthermore, western blotting showed upregulation of glutathione synthetase (GSS), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) in PTBP1KD-BMSCs, known negative regulators of ferroptosis. Moreover, PTBP1KD-BMSCs inhibited p38MAPK and JNK activation. In addition, PTBP1KD-BMSCs transplantation into middle cerebral artery occlusion/reperfusion (MCAO/R) rats reduced cerebral infarction volume and improved neurological function. Immunofluorescence analysis confirmed the upregulation of GSS expression in neurons of the ischemic cortex, while immunohistochemistry indicated a downregulation of p-P38. These result suggest that PTBP1KD-BMSCs can alleviate neuronal IRI by reducing oxidative stress, inhibiting ferroptosis, and modulating the MAPK pathway, providing a theoretical basis for potential treatment strategies for cerebral IRI. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pyroptosis-related genes upregulate in brain cell clusters concurrently after MCAO. • MANF inhibits pyroptosis. • Manf -modified BMSCs play a strong therapeutic role in cerebral infarction. Cerebral infarction is a common disease characterized by high mortality, a narrow therapeutic window, and limited therapeutic options. Recently, cell therapy based on gene modification has brought a glimmer of hope to the treatment of cerebral infarction although the explicit underlying mechanism is beyond being well dissected. In the present study, we constructed an animal model of middle cerebral artery occlusion (MCAO), compared differentially expressed genes (DEGs) between the sham and MCAO groups by single-cell RNA sequencing (scRNA-seq) to explore the potential cell death-related pathways involved in cerebral infarction, and transfected Manf into BMSCs by lentivirus. Subsequently, we injected BMSCs (bone marrow-derived mesenchymal stem cells), Manf -modified BMSCs, or lentivirus encoding Manf into the brain. Their effects on MANF content, apoptosis, pyroptosis, infarct volume in the brain, and neurological function were evaluated after MCAO. We found that the DEGs upregulated in four major cell clusters after MCAO and were enriched with not only apoptosis, ferroptosis, and necroptosis but also with pyroptosis-related pathways. In addition, transfection of Manf into BMSCs significantly increased the expression and secretion of MANF in BMSCs; BMSCs, Manf -modified BMSCs, and Manf treatment all resulted in an increase in Manf content in the brain, a decrease in the expression of apoptosis- and pyroptosis-related molecules, a reduction in infarct volume, and an improvement in neurological function after MCAO. Moreover, Manf -modified BMSCs have the strongest therapeutic effect. Collectively, Manf -modified BMSCs ameliorate ischemic injury after cerebral infarction by repressing apoptosis- and pyroptosis-related molecules, which represents a new cell therapy strategy for cerebral infarction. [ABSTRACT FROM AUTHOR]

The relationship between the fine structure of starch and its gelatinization properties is not well studied, particularly in relation to the influence of sugar or sugar alcohol. In this study, seven starches with distinct molecular structures were investigated to determine how different sugars and sugar alcohols affect their gelatinization properties. The inclusion of sugars and sugar alcohols resulted in a significant elevation of starch gelatinization temperatures (∼ 8 °C), especially with sucrose, isomaltose and isomalt. Nevertheless, the influence of these sugars/ sugar alcohols on the gelatinization temperature range and enthalpy change varied depending on the particular starch varieties. According to the correlation analysis, sugars and sugar alcohols mainly exert their impact on the starch gelatinization temperature range and enthalpy change by possibly interacting with amylose chains possessing a degree of polymerization ranging from 100 to 1000 (p < 0.05) and inhibiting the amylose leaching during gelatinization. These findings help a better understanding of the complex relationship between starch fine structure and gelatinization properties under the influence of sugars and sugar alcohols. Possible mechanism how sugars and sugar alcohols affect starch gelatinization property. [Display omitted] [ABSTRACT FROM AUTHOR]

Stroke is a major life-threatening and disabling disease with a restricted therapeutic approach. Bone marrow stromal cells (BMSCs) possess proliferative ability and a multi-directional differentiation potential, and secrete a range of trophic/growth factors that can protect neurons after cerebral ischemia/reperfusion. Transient receptor potential canonical (TRPC) is a family of non-selective channels permeable to Ca2+, with several functions including neuronal survival. Over-expression of TRPC6, a subtype of the TRPC family, was shown to protect neurons against cerebral ischemia/reperfusion injury. However, it remains unclear whether over-expression of TRPC6 in BMSCs can further reduce brain injury after ischemia/reperfusion. In the present study, we report that over-expression of TRPC6 via a CRISPR-based synergistic activation mediator in BMSCs provided a greater reduction of brain injury in a rat model of ischemia/reperfusion. Further, the improved neurofunctional outcomes were associated with increased TRPC6 and brain derived neurotrophic factor expression levels. Overall, these data suggest that TRPC6 over-expressing BMSCs may be a promising therapeutic agent for ischemic stroke. • A new neuronal protective strategy for treatment in ischemic stroke. • Over-expression of TRPC6 in BMSCs via CRISPR/Cas9 based Synergistic Activation mediator. • TRPC6 over-expressed BMSCs alleviated brain injury after ischemia/reperfusion via TRPC6/CREB pathway. • TRPC6 over-expressed BMSCs relieved brain damage after ischemia/reperfusion via increased BDNF protein level. [ABSTRACT FROM AUTHOR]

Abstract: Under many circumstances, motor memory needs to be retained for a long period of time to enable accurate behavior. Since the first introduction of the saccadic adaptation paradigm in 1960s, saccadic adaptation protocols have been widely used to study the mechanisms of motor learning and motor memory. However, previous studies reported that the effect of saccadic adaptation on the oculomotor system was rather short (minutes to hours) in human and non-human primates. Here we ask whether the fast decay of the effects of saccadic adaptation is due to the influence of environmental context. To test this hypothesis, we asked human subjects to perform a saccadic adaptation task in a very dark environment. Our data showed that saccade gain remained at the post-adaptation level 24–72h after exposure to the saccadic adaptation task without significant recovery, and that the effect of saccadic adaptation on saccade gain could still be found 2 months later, much longer than previously reported. Our results indicate a vital role for environmental context in the retention of saccadic adaptation. [Copyright &y& Elsevier]