A Digital Intervention to Promote Self-Management Self-Efficacy Among Community-Dwelling Individuals With Stroke: Pilot Randomized Controlled Trial.

BACKGROUND: Digital interventions provided through smartphones or the internet that are guided by a coach have been proposed as promising solutions to support the self-management of chronic conditions. However, digital intervention for poststroke self-management is limited; we developed the interactive Self-Management Augmented by Rehabilitation Technologies (iSMART) intervention to address this gap. OBJECTIVE: This study aimed to examine the feasibility and initial effects of the iSMART intervention to improve self-management self-efficacy in people with stroke. METHODS: A parallel, 2-arm, nonblinded, randomized controlled trial of 12-week duration was conducted. A total of 24 participants with mild-to-moderate chronic stroke were randomized to receive either the iSMART intervention or a manual of stroke rehabilitation (attention control). iSMART was a coach-guided, technology-supported self-management intervention designed to support people managing chronic conditions and maintaining active participation in daily life after stroke. Feasibility measures included retention and engagement rates in the iSMART group. For both the iSMART intervention and active control groups, we used the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure to assess the feasibility, acceptability, and appropriateness, respectively. Health measures included the Participation Strategies Self-Efficacy Scale and the Patient-Reported Outcomes Measurement Information System's Self-Efficacy for Managing Chronic Conditions. RESULTS: The retention rate was 82% (9/11), and the engagement (SMS text message response) rate was 78% for the iSMART group. Mean scores of the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure were 4.11 (SD 0.61), 4.44 (SD 0.73), and 4.36 (SD 0.70), respectively, which exceeded our benchmark (4 out of 5), suggesting high feasibility, acceptability, and appropriateness of iSMART. The iSMART group showed moderate-to-large effects in improving self-efficacy in managing emotions (r=0.494), symptoms (r=0.514), daily activities (r=0.593), and treatments and medications (r=0.870), but the control group showed negligible-to-small effects in decreasing self-efficacy in managing emotions (r=0.252), symptoms (r=0.262), daily activities (r=0.136), and treatments and medications (r=0.049). In addition, the iSMART group showed moderate-to-large effects of increasing the use of participation strategies for management in the home (r=0.554), work (r=0.633), community (r=0.673), and communication activities (r=0.476). In contrast, the control group showed small-to-large effects of decreasing the use of participation strategies for management in the home (r=0.567), work (r=0.342, community (r=0.215), and communication activities (r=0.379). CONCLUSIONS: Our findings support the idea that iSMART was feasible to improve poststroke self-management self-efficacy. Our results also support using a low-cost solution, such as SMS text messaging, to supplement traditional therapeutic patient education interventions. Further evaluation with a larger sample of participants is still needed. TRIAL REGISTRATION: ClinicalTrials.gov 202004137; https://clinicaltrials.gov/study/NCT04743037?id=202004137&rank=1.

The association between blue light exposure and incidence of type 2 diabetes: A prospective study of UK biobank.

BACKGROUND: Type 2 diabetes (T2D) is the most common type of diabetes. However, research on the relationship between blue light exposure and diabetes development is limited. OBJECTIVE: The present study aimed to investigate the relationship between blue light exposure and T2D incidence and whether it is affected by sleep duration, physical activity, outdoor activity time, and genetic susceptibility. METHODS: A total of 471,686 participants without diabetes were recruited from the UK Biobank cohort. T2D incidence was assessed using hospital inpatient records. Blue light exposure was calculated based on the time spent watching TV, using a computer, and playing computer games, which was determined using an online questionnaire. Cox proportional hazards regression models were used to assess the survival relationship between blue light exposure and T2D, as well as the potential modification effects. RESULT: A total of 18,738 cases of T2D were documented during the median follow-up of 13.04 years. After adjusting for potential confounders, the participants with heavy blue light exposure had a greater risk of T2D compared to those with mild blue light exposure (hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.12-1.23). A significant association between blue light exposure and T2D risk was observed among the participants with heavy physical activity (HR = 1.39, 95%CI: 1.25-1.55), healthy sleep habits (HR = 1.23, 95%CI: 1.10-1.36), higher outdoor activity time (HR = 1.14, 95%CI: 1.07-1.22), or high genetic susceptibility (HR = 1.24, 95%CI: 1.14-1.35). However, this association became non-significant among the participants with low genetic susceptibility (HR = 1.05, 95%CI: 0.97-1.15). CONCLUSION: The present study showed that blue light exposure is associated with a greater risk of T2D independent of classical T2D risk factors.

Circular RNA hsa_circ_0001846 facilitates the malignant behaviors of pancreatic cancer by sponging miR-204-3p and upregulating KRAS expression.

Pancreatic cancer (PC) is mainly derived from the exocrine pancreatic ductal epithelial cells, and it is strongly aggressive malignant tumor. Due to its insidious onset and the lack of effective diagnostic biomarkers, PC currently remains one of the main causes of cancer-related mortality worldwide. Recent studies have found that hsa_circ_0001846 is involved in the progression of multiple cancers and has the potential to become biomarkers, but its function and mechanism in PC remains unclear. We found by qRT-PCR experiments that hsa_circ_0001846 was upregulated in PC cells and tissues, while circBase, Sanger sequencing, agarose gel electrophoresis and FISH experiments identified the splicing site, ring structure and cellular localization of hsa_circ_0001846. Various functional experiments by using the construction of small interfering RNA targeting hsa_circ_0001846 and overexpression plasmid demonstrated that hsa_circ_0001846 promoted the proliferation, migration and invasion of PC cells. Moreover, the tumor weight and volume of nude mice were significantly reduced after the stable knockdown of hsa_circ_0001846. In the mechanism exploration, RNA pull-down experiments and dual-luciferase experiments helped us to determine that hsa_circ_0001846 regulated the KRAS expression by sponging miR-204-3p in PC, thus playing a pro-cancer role. In this study, the effect of miR-204-3p on PC was also explored for the first time, and we found that knockdown of miR-204-3p reversed the tumor suppressive effect caused by silencing hsa_circ_0001846, and silencing KRAS also rescued the pro-cancer effect caused by overexpression of hsa_circ_0001846. In conclusion, our study revealed the pro-cancer role of hsa_circ_0001846 in PC, and for the first time identified the mechanism that hsa_circ_0001846 regulated KRAS by sponging miR-204-3p to promote PC progression and had the potential to become a cancer biomarker.

A topochemical reaction induced the formation of Bi2S3 micro-straws from a Bi-MOF for an ultra-long Zn storage life.

Aqueous zinc ion batteries (ZIBs) are considered as promising energy storage devices in the post-lithium-ion era, due to their high energy density, low cost, high safety, and environmental benignity, however their commercialization is hindered by the sluggish diffusion kinetics of cathode materials due to the large hydrate Zn2+ radius. In this work, we propose a unique structure inheritance strategy for preparing Bi2S3 micro-straws in which a metal-organic framework (MOF) denoted as Bi-PYDC (PYDC2- = 3,5-pyridinedicarboxylate) with a string of [Bi2O2]2+ chains is judiciously selected as the structure-directing template to induce the formation of micro-straws based on a topochemical reaction. The distinctive hollow structure significantly enhances the ionic storage kinetics. Impressively, the obtained battery exhibits an ultra-long cycle life of more than 10 000 cycles at a current density of 1 A g-1 while maintaining a capacity of more than 153.4 mA h g-1. In addition, the Zn2+ insertion/extraction mechanism of Bi2S3 micro-straws is also investigated by multiple analytical methods, revealing the involvement of Zn2+ rather than H+ in the electrochemical storage process. This work may lead a new direction for constructing high performance cathodes of Zn-ion batteries through a MOF-based structure-directing template.

A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

Constructing a prognostic risk model for Alzheimer's disease based on ferroptosis.

Introduction: The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer's disease (AD) through gene expression changes. Methods: The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aß1-42 on the expression profile of representative genes in vitro. Results: Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aß1-42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aß1-42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased. Discussion: The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer's disease.

Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression.

Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.

Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage.

Sphingosine kinase 1 (SphK1) is an important signaling molecule for cell proliferation and survival. However, the role of SphK1 in acrylamide (ACR)-induced nerve injury remains unclear. The purpose of this study was to investigate the role and potential mechanism of SphK1 in ACR-induced nerve injury. Liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and reverse transcription-quantitative PCR (RT-qPCR) were used to detect sphingosine 1-phosphate (S1P) content in serum and SphK1 content in whole blood from an occupational work group exposed to ACR compared to a non-exposed group. For in vitro experiments, SphK1 in human SH-SY5Y neuroblastoma cells was activated using SphK1-specific activator phorbol 12-myristate 13-acetate (PMA). Our research also utilized cell viability assays, flow cytometry, western blots, RT-qPCR and related protein detection to assess activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results of the population study showed that the contents of SphK1 and S1P in the ACR-exposed occupational contact group were lower than in the non-exposed group. The results of in vitro experiments showed that expression of SphK1 decreased with the increase in ACR concentration. Activating SphK1 improved the survival rate of SH-SY5Y cells and decreased the apoptosis rate. Activating SphK1 in SH-SY5Y cells also regulated MAPK signaling, including enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK) and inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and p38. These results suggest that activating SphK1 can protect against nerve cell damage caused by ACR.

Revealing the binding properties between resorcinol and DNA.

Resorcinol (1,3-dihydroxybenzene) is a common coupling agent in permanent hair dyes, and has arrested people's attention for its potential hazard to human health. However, the action mechanism of resorcinol and human DNA has not been elucidated. In this research, the binding properties between resorcinol and calf thymus DNA (ct-DNA) were studied for the first time through various spectral and molecular docking techniques. Spectral studies showed that the initial fluorescence quenching of resorcinol against DNA was a static one. The result of ΔH < 0 and ΔS > 0 was produced from thermodynamic experimental data, therefore it could be concluded that electrostatic force was the major driving force, while binding constant Kb was 1.56 × 104 M-1 at 298 K. The electrostatic binding network between resorcinol and ct-DNA was established explicitly through competitive substitution analysis and other spectral approaches. The results of FT-IR absorption spectra indicated that resorcinol had bound to the DNA phosphate skeleton. Molecular docking clearly revealed that binding occurred between hydroxyl groups of resorcinol and phosphorus oxygen bonds (P-O) of the DNA skeleton. These findings may deepen our understanding of the action mechanism between resorcinol and ct-DNA and provide some useful data on the effect of resorcinol on human diseases.

Simultaneous optimization of ultrasound-assisted extraction for total flavonoid content and antioxidant activity of the tender stem of Triarrhena lutarioriparia using response surface methodology.

The asparagus of Triarrhena lutarioriparia (TL) is a popular vegetable with abundant chemical compounds in China. This study aims to optimize the ultrasound-assisted extraction (UAE) method for its content of total flavonoid and antioxidant activities by response surface methodology (RSM). Box-Behnken design was adopted to evaluate the influences of ethanol concentration, extraction time and solvent-to-sample ratio on the extraction yield of total flavonoid and the antioxidant activity. Considering the maximum content of extracted total flavonoids and antioxidant activity, the optimal extraction conditions were acquired with 70% (v/v) ethanol by UAE for 60 min at a solvent-to-sample ratio of 40 mL/g. The proportion of the extraction of total flavonoid was 15.88 mg/g and antioxidant activity reached 79.53%. The RSM would be recommended as an appropriate model for simultaneous optimization of the UAE conditions for the content of total flavonoid and the antioxidant activity of asparagus of TL.

Quantitative analysis of multicomponents by single marker combined with HPLC fingerprint qualitative analyses for comprehensive evaluation of Aurantii Fructus.

The present study aimed to develop a strategy involving quantitative analysis of multicomponents by single marker in combination with high-performance liquid chromatography fingerprint qualitative analysis for performing the quality control of Aurantii Fructus. The content of 12 components (eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, meranzin, poncirin, naringenin, nobiletin, tangeretin, and auraptene) in samples was determined using reliable relative correction factors that were obtained using naringin as an internal reference standard. The new method demonstrated good applicability, and no significant differences were observed between the external standard method and the new method as determined by calculating standard method difference. Qualitative evaluation of samples was conducted using similarity analysis, hierarchical cluster analysis, and quality fluctuation analysis. Chromatographic fingerprint data were divided into three groups by similarity and hierarchical cluster analyses, and seven components may have a more significant impact on the quality of Aurantii Fructus in quality fluctuation analysis. Overall, the study suggests that the qualitative and quantitative analyses of multicomponents using quantitative analysis of multicomponents by single marker combined with chromatographic fingerprinting can be considered good quality criteria for performing quality control and providing technical support for the further pharmacological and pharmaceutical research of Aurantii Fructus.

Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons.

In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP) in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca(2+)-activated non-selective cation (CAN) current (ICAN ) that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca(2+)-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN , remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential (TRP) melastatin 5 channel (TRPM5), which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

Two Gr genes underlie sugar reception in Drosophila.

We have analyzed the molecular basis of sugar reception in Drosophila. We define the response spectrum, concentration dependence, and temporal dynamics of sugar-sensing neurons. Using in situ hybridization and reporter gene expression, we identify members of the Gr5a-related taste receptor subfamily that are coexpressed in sugar neurons. Neurons expressing reporters of different Gr5a-related genes send overlapping but distinct projections to the brain and thoracic ganglia. Genetic analysis of receptor genes shows that Gr5a is required for response to one subset of sugars and Gr64a for response to a complementary subset. A Gr5a;Gr64a double mutant shows no physiological or behavioral responses to any tested sugar. The simplest interpretation of our results is that Gr5a and Gr64a are each capable of functioning independently of each other within individual sugar neurons and that they are the primary receptors used in the labellum to detect sugars.

Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin-PKA-Ena/VASP pathway.

Syndecan-2 induced filopodia before spinogenesis; therefore, filopodia formation was used here as a model to study the early downstream signaling of syndecan-2 that leads to spinogenesis. Screening using kinase inhibitors indicated that protein kinase A (PKA) is required for syndecan-2-induced filopodia formation in both human embryonic kidney cells and hippocampal neurons. Because neurofibromin, a syndecan-2-binding partner, activates the cyclic adenosine monophosphate pathway, the role of neurofibromin in syndecan-2-induced filopodia formation was investigated by deletion mutant analysis, RNA interference, and dominant-negative mutant. The results showed that neurofibromin mediates the syndecan-2 signal to PKA. Among actin-associated proteins, Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) were predicted as PKA effectors downstream of syndecan-2, as Ena/VASP, which is activated by PKA, induces actin polymerization. Indeed, when the activities of Ena/VASP were blocked, syndecan-2 no longer induced filopodia formation. Finally, in addition to filopodia formation, neurofibromin and Ena/VASP contributed to spinogenesis. This study reveals a novel signaling pathway in which syndecan-2 activates PKA via neurofibromin and PKA consequently phosphorylates Ena/VASP, promoting filopodia and spine formation.