Assessing the impact of message relevance and frequency on physical activity change: A secondary data analysis from the random AIM trial.

Text messages are widely used to deliver intervention content; however, sending more intensive messages may not always improve behavioral outcomes. This study investigated whether message frequency was associated with daily physical activity, either by itself or in interaction with message content relevance. Healthy but insufficiently active young adults (aged 18-29 years) wore Fitbit activity trackers and received text messages for 180 days. Message frequencies varied daily at random, and messages were sent from three content libraries (40% Move More, 40% Sit Less, 20% Inspirational Quotes). Contrary to expectations, the results revealed a null association between total daily text message frequency and physical activity, both for daily step counts and moderate-to-vigorous physical activity (MVPA) duration. Additional analyses revealed that the daily frequency of messages with relevant content (i.e. Move More, Sit Less) was not associated with physical activity, but the daily frequency of messages with irrelevant content (i.e. Inspirational Quotes) was negatively associated with physical activity. We concluded that the effectiveness of text messages in promoting physical activity is impacted by the combination of content relevance and frequency, with frequent irrelevant messages potentially decreasing activity levels. This study suggests that irrelevant message frequency can negatively impact physical activity, highlighting the risks of delivering irrelevant content in digital health interventions.

Wearable device adherence among insufficiently-active young adults is independent of identity and motivation for physical activity.

Wearable devices are increasingly being integrated to improve prevention, chronic disease management and rehabilitation. Inferences about individual differences in device-measured physical activity depends on devices being worn long enough to obtain representative samples of behavior. Little is known about how psychological factors are associated with device wear time adherence. This study evaluated associations between identity, behavioral regulations, and device wear adherence during an ambulatory monitoring period. Young adults who reported insufficient physical activity (N = 271) were recruited for two studies before and after the SARS-COVID-19 pandemic declaration. Participants completed a baseline assessment and wore an Actigraph GT3X + accelerometer on their waist for seven consecutive days. Multiple linear regression indicated that wear time was positively associated with age, negatively associated with integrated regulation for physical activity, and greater after (versus before) the pandemic declaration. Overall, the model accounted for limited variance in device wear time. Exercise identity and exercise motivation were not associated with young adults' adherence to wearing the physical activity monitors. Researchers and clinicians can use wearable devices with young adults with minimal concern about systematic motivational biases impacting adherence to device wear.

Transcriptional and epigenetic decoding of the microglial aging process.

As important immune cells, microglia undergo a series of alterations during aging that increase the susceptibility to brain dysfunctions. However, the longitudinal characteristics of microglia remain poorly understood. In this study, we mapped the transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We first discovered unexpected sex differences and identified age-dependent microglia (ADEM) genes during the aging process. We then compared the features of aging and reactivity in female microglia at single-cell resolution and epigenetic level. To dissect functions of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged-like microglia in non-aged brains and confirmed that aged-like microglia per se contribute to cognitive decline. Collectively, our work provides a comprehensive resource for decoding the aging process of microglia, shedding light on how microglia maintain brain functions.

Dose-response relations between the frequency of two types of momentary feedback prompts and daily physical activity.

OBJECTIVE: Self-monitoring and behavioral feedback are widely used to help people monitor progress toward daily physical activity goals. Little information exists about the optimal dosing parameters for these techniques or if they are interchangeable in digital physical activity interventions. This study used a within-person experimental design to evaluate associations between the frequency of two different prompt types (one for each technique) and daily physical activity. METHOD: Insufficiently active young adults were assigned monthly physical activity goals and wore smartwatches with activity trackers for 3 months. They received zero to six randomly selected and timed watch-based prompts each day, with individual prompts either providing behavioral feedback or prompting the participant to self-monitor. RESULTS: Physical activity increased significantly over the 3-month period (step counts d = 1.03; moderate-to-vigorous physical activity duration d = 0.99). Mixed linear models revealed that daily step counts were positively associated with the frequency of daily self-monitoring prompts up to approximately three prompts/day (d = 0.22) after which additional prompts provided minimal or reduced benefit. Daily step counts were not associated with the frequency of behavioral feedback prompts. Daily moderate-to-vigorous physical activity was not associated with the frequency of either prompt. CONCLUSIONS: Self-monitoring and behavioral feedback are not interchangeable behavior change techniques in digital physical activity interventions, and only self-monitoring prompts show signs of a dose-response association with physical activity volume. Activity trackers, such as smartwatches and mobile apps, should provide an option to replace behavioral feedback prompts with self-monitoring prompts to promote physical activity among insufficiently active young adults. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury.

The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague-Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague-Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-ß-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.

Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution.

PURPOSE: To investigate the incidence rate of hereditary disease in patients with medulloblastoma. METHODS: The genetic reports of 129 patients with medulloblastoma from January 2016 to December 2019 were retrospectively analyzed. A panel sequence of 39 genes (Genetron Health) were used for all patients to evaluate the tumor subgroup. Four genes (TP53, APC, PTCH1, SUFU) were screened to routinely rule out germline mutation. RESULTS: Five patients (3.9%) were found with hereditary disease, and all belonged to the sonic hedgehog (SHH) subgroup. Two patients were retrospectively diagnosed with Gorlin-Goltz disease with germline PTCH1 and SUFU mutations. One patient (PTCH1 mutation) accepted whole craniospinal irradiation and had scalp nevoid basal cell carcinoma 5 years later. The other patient (SUFU mutation) accepted chemotherapy and had local tumor relapse 1 year later. Three patients were diagnosed with Li-Fraumeni syndrome and carried the TP53 mutation; all three patients died. One of the patients had bone osteosarcoma, while all three had early tumor relapse. CONCLUSION: Patients with SHH medulloblastoma should routinely undergo genetic testing. We propose that whole genome, whole exome sequence, or custom-designed panel-targeted exome sequencing should be performed.

Bexarotene promotes microglia/macrophages - Specific brain - Derived Neurotrophic factor expression and axon sprouting after traumatic brain injury.

Traumatic brain injury (TBI) has been regarded as one of the leading cause of injury-related death and disability. White matter injury after TBI is characterized by axon damage and demyelination, resulting in neural network impairment and neurological deficit. Brain-derived neurotrophic factor (BDNF) can promote white matter repair. The activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to promote microglia/macrophages towards anti-inflammatory state and therefore to promote axon regeneration. Bexarotene, an agonist of retinoid X receptor (RXR), can activate RXR/PPARγ heterodimers. The aim of the present study was to identify the effect of bexarotene on BDNF in microglia/macrophages and axon sprouting after TBI in mice. Bexarotene was administered intraperitoneally in C57BL/6 mice undergoing controlled cortical impact (CCI). PPARγ dependency was determined by intraperitoneal administration of a PPARγ antagonist T0070907. We found that bexarotene promoted axon regeneration indicated by increased growth associated protein 43 (GAP43) expression, myelin basic protein (MBP) expression, and biotinylated dextran amine (BDA)+ axon sprouting. Bexarotene also increased microglia/macrophages-specific brain derived neurotrophic factor (BDNF) expression after TBI. In addition, bexarotene reduced the number of pro-inflammatory microglia/macrophages while increased the number of anti-inflammatory microglia/macrophages after TBI. Moreover, bexaortene inhibited pro-inflammatory cytokine secretion. In addition, bexarotene treatment improved neurological scores and cognitive function of CCI-injured mice. These effects of bexarotene were partially abolished by T0070907. In conclusion, bexarotene promotes axon sprouting, increases microglia/macrophages-specific BDNF expression, and induces microglia/macrophages from a pro-inflammatory state towards an anti-inflammatory one after TBI at least partially in a PPARγ-dependent manner.

Upregulation of miRNA-9-5p Promotes Angiogenesis after Traumatic Brain Injury by Inhibiting Ptch-1.

MicroRNA-9-5p (miRNA-9-5p) is an important regulator of angiogenesis in many pathological states. However, the effect of miRNA-9-5p on angiogenesis after traumatic brain injury (TBI) has not been elucidated. In this study, a controlled cortical impact (CCI) model was used to induce TBI in Sprague-Dawley rats, and an oxygen glucose deprivation (OGD) model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) were extracted from immature rats. The results showed that the level of miRNA-9-5p was significantly increased in the traumatic foci after TBI, and the upregulation of miRNA9-5p promoted the recovery of neurological function. Moreover, the upregulation of miRNA-9-5p with miRNA agomir significantly increased the density of the microvascular and neurons around the traumatic foci in rats after TBI. The results of the in vitro experiments confirmed that the upregulation of miRNA-9-5p with a miRNA mimic improved cellular viability and alleviated cellular apoptosis. Dual luciferase reporter assay validated that miRNA-9-5p was a posttranscriptional modulator of Ptch-1. Activation of the Hedgehog pathway by increasing the level of miRNA-9-5p promoted the migration and tube formation of BMECs in vitro. In addition, we found that the upregulation of miRNA-9-5p activated the Hedgehog pathway and increased the phosphorylation of AKT, which promoted the expression of cyclin D1, MMP-9 and VEGF in BMECs. All these results indicate that the upregulation of miRNA-9-5p promotes angiogenesis and improves neurological functional recovery after TBI, mainly by activating the Hedgehog pathway. MiRNA-9-5p may be a potential new therapeutic target for TBI.

Activation of the Hedgehog Pathway Promotes Recovery of Neurological Function After Traumatic Brain Injury by Protecting the Neurovascular Unit.

The homeostasis of the neurovascular unit (NVU) is disrupted after traumatic brain injury (TBI), and therapeutic strategies targeting the NVU would likely improve neurological outcomes after TBI. Sonic Hedgehog (Shh), which is an endogenous activator of the Hedgehog pathway, promotes brain repair in various injuries. In this study, the controlled cortical impact (CCI) was used to establish a moderate TBI model in adult male Sprague-Dawley rats (250-300 g), and the NVU was reconstructed in vitro from the blood-brain barrier (BBB) and neurons to investigate the effects of exogenous Shh protein on TBI. The modified neurological severity scores (mNSS) and Morris water maze tests were used to evaluate the effect of Shh on neurological function after TBI. The effect of Shh on the NVU in vivo was evaluated by detecting the degrees of cerebral edema and neuronal apoptosis. The integrity and permeability of the BBB, the level of inflammatory factors, and the expression of apoptotic proteins were detected to explore the effect of exogenous Shh on the NVU in vitro. The results showed that exogenous Shh reduced cerebral edema and neuronal apoptosis and promoted neurological recovery after TBI in rats. In vitro experiments showed that Shh-induced activation of the Hedgehog pathway promoted stability of the NVU by reducing damage to the tight junction structure and inhibiting the release of inflammatory factors and neuron apoptosis. Based on these results, the Shh-induced activation of the Hedgehog pathway might be a new promising treatment for TBI.

microRNA-9-5p alleviates blood-brain barrier damage and neuroinflammation after traumatic brain injury.

The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed after traumatic brain injury (TBI). However, the effect of miRNA-9-5p for brain function in TBI has not been elucidated. In this study, a controlled cortical impact model was used to induce TBI in Sprague-Dawley rats, and an oxygen glucose deprivation model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) and astrocytes were extracted from immature Sprague-Dawley rats and cocultured to reconstruct blood-brain barrier (BBB) in vitro. The results show that the level of miRNA-9-5p was significantly increased in brain tissues after TBI, and up-regulation of miRNA9-5p contributed to the recovery of neurological function. Up-regulation of miRNA-9-5p with miRNA agomir may significantly alleviate apoptosis, neuroinflammation, and BBB damage in rats after TBI. Moreover, a dual luciferase reporter assay confirmed that miRNA-9-5p is a post-transcriptional modulator of Ptch-1. In in vitro experiments, the results confirmed that up-regulation of miRNA-9-5p with miRNA mimic alleviates cellular apoptosis, inflammatory response, and BBB damage mainly by inhibiting Ptch-1. In addition, we found that the activation of Hedgehog pathway was accompanied by inhibition of NF-κB/MMP-9 pathway in the BMECs treated with miRNA-9-5p mimic. Taken together, these results indicate that up-regulation of miRNA-9-5p alleviates BBB damage and neuroinflammatory responses by activating the Hedgehog pathway and inhibiting NF-κB/MMP-9 pathway, which promotes the recovery of neurological function after TBI.

Bexarotene protects against neurotoxicity partially through a PPARγ-dependent mechanism in mice following traumatic brain injury.

Traumatic brain injury (TBI) causes a high rate of mortality and disability worldwide, and there exists almost none effective drugs to protect against TBI. Neurotoxicity occurring after TBI can be derived from microglia and astrocytes, and causes neuronal death and synapse loss. Bexarotene has been demonstrated to protect neurons in CNS diseases. In the present study, we aimed to investigate the potential role of bexarotene in protecting against neurotoxicity after TBI, as well as the underlying mechanism. The controlled cortical impact (CCI) model was established on adult C57BL/6 mice, followed by intraperitoneal administration of bexarotene for 14 consecutive days. We found that bexarotene improved sensorimotor function and cognitive recovery in CCI mice. In addition, bexarotene decreased neuronal death and synapse loss, as well as inhibited apoptotic cascade. Moreover, bexarotene treatment reduced M1 microglia polarization, microglia-derived pro-inflammatory cytokines, and the number of A1 astrocytes after CCI. These effects of bexarotene were partially abolished by T0070907, an antagonist of peroxisome proliferator-activated receptor gamma (PPARγ). Additionally, bexarotene enhanced nuclear translocation and transcriptional activity of PPARγ. These findings show that bexarotene inhibits neurotoxicity in mice after TBI, at least in part through a PPARγ-dependent mechanism.

The long non-coding RNA Neat1 is an important mediator of the therapeutic effect of bexarotene on traumatic brain injury in mice.

OBJECTIVE: Bexarotene treatments exert neuroprotective effects on mice following traumatic brain injury (TBI). The present study aims to investigate the potential roles of the long noncoding RNA Neat1 in the neuroprotective effects of bexarotene. MATERIALS AND METHODS: Adult male C57BL/6J mice (n=80) and newborn mice (within 24h after birth) (n=20) were used to generate a "controlled cortical impact" (CCI) model and harvest primary cortex neurons, respectively. The HT22 cell line and the BV2 cell line were cultured under "normal" or "oxygen/glucose-deprived" (OGD) conditions. The relationship between RXR-α and the Neat1 promoter was clarified using ChIP-qPCR and dual-luciferase reporter gene assays. The mRNA alterations induced by Neat1 knockdown were measured using next-generation RNA sequencing. Proteins were captured by Neat1, pulled down and subjected to mass spectrometry. The neurological severity score, rotarod test and water maze test were employed to measure the animals' motor and cognitive functions. RESULTS: Bexarotene prominently up-regulated the Neat1 level in an RXR-α-dependent manner. Neat1 knockdown induced significant changes in mRNA expression, and the altered mRNAs were involved in many biological processes, including synapse formation and axon guidance. In primary neurons, Neat1 knockdown inhibited and Neat1 over-expression prompted axon elongation. Multiple proteins, including Pidd1, were captured by Neat1. Neat1 inhibited cell apoptosis and restricted inflammation by capturing Pidd1. The in vitro anti-apoptotic and anti-inflammatory effects of Neat1 were further confirmed in C57BL/6 mice, which resulted in better motor and cognitive function after TBI. CONCLUSION: Bexarotene up-regulates the lncRNA Neat1, which inhibits apoptosis and inflammation, thereby resulting in better functional recovery in mice after TBI.

PPARß/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats.

Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor ß/δ (PPARß/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARß/δ in VSMC phenotypic switch following SAH. Activation of PPARß/δ by GW0742 and adenoviruses PPARß/δ (Ad-PPARß/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARß/δ on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPARß/δ-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that Ad-PPARß/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARß/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARß/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia.

AIEE-Active and Electrochromic Bifunctional Polymer and a Device Composed thereof Synchronously Achieve Electrochemical Fluorescence Switching and Electrochromic Switching.

A novel alternating polymer, ProDOT-TPE, with aggregation-enhanced fluorescent emission and electrochromic properties based on thiophene and tetraphenylethene derivatives was designed, synthesized, and characterized. The polymer displays weak photoluminescence in tetrahydrofuran, but its corresponding film prepared by spray-coating exhibits yellow-green fluorescent light at 540 nm. The color of the polymer film could be switched from bright yellow to navy blue by applying a relatively low voltage. An electrochromic device (ECD) of the polymer was fabricated that differs from common ECDs because both its color and fluorescent state could be synchronously switched by an applied voltage, making the polymer a unique candidate for electrochemical fluorescence and electrochromic applications.

The study of influence factors on (131)I treatment of differentiated thyroid carcinoma with lymph node metastases.

OBJECTIVE: Thyroid carcinoma is the most common malignant endocrine tumor, which comprises 1% in all human tumors. As for differentiated thyroid carcinoma (DTC), lymph nodes are the most common metastatic site for which the major treatment is (131)I therapy. This retrospective study aimed to investigate the therapeutic effect and analyze the influence factors on (131)I treatment of DTC with lymph node metastases. METHODS: Collecting clinical data of 66 DTC patients with lymph node metastases at the Department of Nuclear Medicine, Xin Hua Hospital from January 1996 to January 2006. Investigating the therapeutic effect firstly and then dividing 66 patients into an eliminated group and an uneliminated group according to the evaluation criteria of the therapeutic effect. Finally, observing the differences between the two groups. The significant differences in the following 10 influence factors were determined: gender, age, pathological type, the periods from the thyroidectomy to the first (131)I therapy, when the metastases were found, the history of resection of the lymph node metastases, the uptake of (18)F-FDG in the lymph node metastases, remnant thyroid, multiple metastases, and the cumulative dose of (131)I. This retrospective study was analyzed by Student t test, chi(2) test, and Fisher's exact test. RESULTS: Of all 66 patients with lymph node metastatic DTC treated by (131)I therapy, 31 patients (46.97%) had complete elimination. Twenty-seven patients were improved or controlled, and the overall effective rate reached 87.88%. The elimination rate of lymph node metastases in patients with resection was significantly higher than in those without resection (chi(2)=5.561, P=.018<0.05). The elimination rate of lymph node metastases in patients with (18)F-FDG uptake was significantly higher than in those without (18)F-FDG uptake (chi(2)=4.014, P=.045<.05). There was no significant difference in the elimination rate among the patients with various values in the other eight factors. CONCLUSIONS: (131)I Therapy is an effective treatment of lymph node metastatic DTC. The history of resection of the lymph node metastases and the uptake of (18)F-FDG in the lymph node metastases were the influence factors on the therapeutic effect, whereas the other eight factors were probably not.

The role of single-photon emission computed tomography/computed tomography for precise localization of metastases in patients with differentiated thyroid cancer.

PURPOSE: It is very important in the management of patients with differentiated thyroid cancer (DTC) to precisely localize the foci of I-131 uptake, but it is difficult because of a lack of anatomic landmarks. The purpose of this study was to investigate the added value of I-131 single-photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging using a hybrid system in patients with DTC. METHODS: Ninety-four patients with DTC underwent I-131 SPECT/CT using a hybrid tomography consisting of a dual-head variable-angle gamma camera and a low-dose X-ray tube. Results were compared with I-131 whole-body scan (WBS). SPECT/CT was performed 5-7 days after administration of a therapeutic dose of I-131. Fusion images were constructed by combining the digital CT and SPECT images on a computer workstation. RESULTS: Compared with I-131 WBS, SPECT/CT imaging had improved the precise localization in 21% (20/94) of patients. In addition, SPECT/CT provided additional clinical data in 12 of the patients examined (12/94) and also caused physicians to reconsider the (131)I therapeutic approach in 22 patients. CONCLUSION: The results of the current study indicate that the addition of I-131 SPECT/CT to WBS can improve the localization of metastases in patients with DTC. It may also detect metastases missed by WBS and adjust the therapy plan.