S-Adenosyl-l-Methionine Alleviates the Senescence of MSCs Through the PI3K/AKT/FOXO3a Signaling Pathway.

Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-l-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100 µM for 2 hours), SAM (50 and 100 µM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of reactive oxygen species and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/day d-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/day by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of forkhead box O3 (FOXO3a) was proved to be associated with the antisenescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases.

TAM-Hijacked Immunoreaction Rescued by Hypoxia-Pathway-Intervened Strategy for Enhanced Metastatic Cancer Immunotherapy.

Immunotherapy is regarded as a prospective strategy against metastatic cancer. However, tumor-associated macrophages (TAMs), which accumulate in hypoxic tumor microenvironment, reduce the effectiveness of immunotherapy by blocking or "hijacking" the initiation of the immune response. Here, a novel tumor-targeted nanoplatform loaded with hypoxia-pathway-intervened docosahexaenoic acid (DHA) and chemotherapeutic drug carfilzomib (CFZ) is developed, which realizes the rescue of TAM-hijacked immune response and effective metastatic cancer immunotherapy. DHA is conjugated to fucoidan (Fuc) via a reduction cleavable selenylsulfide bond (SSe) for micelle preparation, and CFZ is encapsulated in the hydrophobic cores of micelles. The functionalized nanoplatforms (Fuc─SSe─DHA (FSSeD)-CFZs) induce immunogenic cell death, inhibit hypoxia-inducible factor-1α expression, and improve immunosuppression by TAM suppression. FSSeD-CFZs enhance immune response against primary tumor development and metastasis formation. In brief, the novel rescue strategy for TAM-hijacked immunoreaction by inhibiting hypoxia pathway has the potential and clinically translational significance for enhanced metastatic cancer immunotherapy.

Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification.

BACKGROUND AND AIM: The aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. METHODS AND RESULTS: A total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0-5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04-3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). CONCLUSIONS: High levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).

Associations of combined lifestyle index with migraine prevalence and headache frequency: a cross-sectional study from the MECH-HK study.

BACKGROUND: Prior research has shown that individual lifestyles were associated with migraine. Yet, few studies focused on combined lifestyles, particularly in Chinese populations. This cross-sectional study aimed to investigate the relationships of a combined lifestyle index with migraine in Hong Kong Chinese women. METHODS: Baseline data from a cohort study named Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) were used for analysis. In total 3510 women aged 55.2 ± 9.1 years were included. The combined lifestyle index comprised eight lifestyle factors: smoking, physical activity, sleep, stress, fatigue, diet, body mass index, and alcohol. Each component was attributed a point of 0 (unhealthy) or 1 (healthy). The overall index was the sum of these points, ranging from 0 (the least healthy) to 8 points (the healthiest). Migraine was diagnosed by the International Classification of Headache Disorders 3rd edition. Additionally, for women with migraine, the data on migraine attack frequency (attacks/month) was collected. RESULTS: A total of 357 women with migraine (10.2%) were identified. The prevalence of migraine for the 0-3-point, 4-point, 5-point, 6-point, and 7-8-point groups were 18.0% (162/899), 10.9% (86/788), 6.6% (51/776), 6.0% (38/636), and 4.9% (20/411), respectively. In the most-adjusted model, compared to the 0-3-point group, the odds ratios and 95% confidence intervals for the 4-point, 5-point, 6-point, and 7-8-point groups were 0.57 (0.43-0.75), 0.33 (0.24-0.46), 0.30 (0.21-0.44), and 0.25 (0.15-0.41), respectively (all p < 0.001). For each component, migraine was significantly associated with sleep, stress, fatigue, and diet; but was unrelated to smoking, physical activity, body mass index, and alcohol. Among women with migraine, per point increase in the combined lifestyle index was associated with a reduced migraine attack frequency (ß = - 0.55; 95% confidence interval = - 0.82, - 0.28; p < 0.001). CONCLUSIONS: A combined lifestyle index was inversely associated with migraine and migraine attack frequency in Hong Kong Chinese women. Adhering to a healthy lifestyle pattern might be beneficial to the prevention of migraine attacks. Conversely, it is also plausible that women with migraine might have a less healthy lifestyle pattern compared to those without headaches.

Association between Obstructive Sleep Apnea and Intracranial Artery Calcification Stratified by Gender and Body Mass Index: A Hospital-Based Observational Study.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial arterial calcification (IAC) has been validated as a marker for subclinical cerebrovascular disease. However, the relationship between OSA with IAC was less studied compared with its established association with coronary artery calcification. In this study, we aimed to investigate the association between the severity of OSA and the degree of IAC in hospitalized patients without preexisting cardiovascular disease. METHODS: This hospital-based observational study was conducted from June 1, 2017, to May 1, 2019. In total, 901 consecutive patients who underwent head computed tomography scans and portable sleep monitoring were included. On the basis of the apnea-hypopnea index (AHI), patients were divided into four OSA severity groups (normal: AHI <5/h; mild: 5≤ AHI <15/h; moderate: 15≤ AHI <30/h; severe: AHI ≥30/h). Associations of OSA with IAC scores were assessed by using multivariate logistic regression analysis. RESULTS: Of the 901 patients, 484 (53.7%) were men; the mean (SD) age was 66.1 (10.0) years. The non-OSA group included 207 (23.0%) patients; mild OSA, 209 (23.2%); moderate OSA, 235 (26.1%); and severe OSA, 169 (18.8%). Mean IAC scores were higher in the severe OSA group compared with non-, mild, and moderate OSA groups (4.79 vs. 2.58; 4.79 vs. 2.94; 4.79 vs. 3.39; p < 0.001). Multivariate analysis adjusted for confounding factors revealed that only severe OSA was associated with a higher IAC score (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.43-1.91; p < 0.001). In stratified analyses by BMI, among participants with a BMI <25 kg/m2, the positive association between AHI values and IAC scores was found in the moderate OSA group (OR: 1.23; 95% CI: 1.05, 1.43; p = 0.01) and the severe OSA group (OR: 1.96; 95% CI: 1.55, 2.48; p < 0.001). When stratified by gender, in women, the positive association was found in the moderate OSA group (adjusted OR: 1.21; 95% CI: 1.02-1.51; p = 0.016) and the severe OSA group (adjusted OR: 1.76; 95% CI: 1.36-2.25; p < 0.001). For the men group, a positive association between IAC scores and AHI was only observed in the severe OSA group. DISCUSSION: These findings suggest that OSA, in particular severe OSA (AHI ≥30), is independently associated with higher IAC scores. Women and no-obesity individuals appeared more susceptible to adverse OSA-related subclinical cerebrovascular disease as measured by IAC scores.

Patterns and Implications of Intracranial Atherosclerosis in Anterior and Posterior Circulation Identified by High-Resolution Vessel Wall Imaging.

INTRODUCTION: Anterior and posterior circulation atheroscleroses differ in vascular risk factors and stroke patterns. Posterior circulation stroke has worse clinical outcomes. However, few studies described the differentiation of plaque features between anterior and posterior circulation atheroscleroses via high-resolution vessel wall imaging (HR-VWI). We aimed to compare the plaque imaging features between anterior and posterior circulations to highlight the relevance of plaque imaging features to clinical events of ischemic stroke. METHODS: Prospective data from a HR-VWI cohort of adult patients with acute ischemic stroke or transient ischemic attack were retrospectively analyzed. Quantitative and qualitative measurements of atherosclerotic plaques along the middle cerebral arteries (MCAs), the basilar artery (BA), and the vertebral arteries (VAs) were conducted on HR-VWI. Vessels with stenotic degrees over 30% were identified on the matched time-of-flight magnetic resonance angiography (TOF-MRA) and visually classified into normal, irregular, stenotic, and occluded. The sensitivity, specificity, positive and negative predictive values for TOF-MRA in detecting abnormal vessels were calculated by using quantification on the basis of HR-VWI findings as the reference standard. RESULTS: One hundred and one patients (median age, 64 years old; 62.4% males) were included in this study. A total of 292 plaques were identified, with 152 in the MCAs, 35 in the BA, and 105 in the VAs. The VAs possessed significantly higher enhancement index (EI) (median 38.37 vs. 18.40, p <0.001), more plaques with positive remodeling (76.2% vs. 57.2%, p = 0.002) and intraplaque hypo-intensity (43.8% vs. 12.5%, p <0.001) than the MCAs. The MCAs presented with more intraplaque hemorrhage (IPH) (20.4% vs. 8.6%, p = 0.014) than the VAs. The sensitivity and specificity of TOF-MRA for evaluating luminal stenosis were 89.0 (82.5-93.4) and 66.7 (24.1-94.0) in anterior circulation, respectively, and were 75.2 (66.7-82.2) and 27.3 (7.3-60.7) in posterior circulation, respectively. CONCLUSION: Our findings might elucidate the clinical events and outcomes in anterior and posterior circulation stroke. Posterior circulation atherosclerosis had higher EI and more plaques with hypo-intensity, suggesting a heavier atherosclerosis burden. Positive remodeling pattern in posterior circulation atherosclerosis might create an impression of "wider" vascular lumen, leading to possible underestimation of atherosclerosis burden of posterior circulation on TOF-MRA as compared to HR-VWI. Besides, anterior circulation atherosclerosis with IPH might be associated with plaque rupture and artery-to-artery embolism. Future studies are needed to verify these findings.

Intracranial artery calcification as an independent predictor of ischemic stroke: a systematic review and a meta-analysis.

BACKGROUND AND PURPOSE: The association between intracranial artery calcification (IAC) and the risk of ischemic stroke occurrence or poor prognosis had not yet been fully understood. In this study, we conducted a meta-analysis of existing studies aimed to assess whether IAC can be used to predict future ischemic stroke and post-stroke mortality. METHODS: Medline, Cochrane, Web of Science and Google Scholar databases were searched up to June 30, 2022. Studies were included if they reported risk ratio (RR) or odds ratios (OR) and corresponding 95% confidence intervals (CI) of stroke concerning the presence of IAC. Random or fixed effects model meta-analyses were performed. Meta-analysis was conducted by using Stata version 16.0. RESULTS: Twelve studies involving 9346 participants were included. Compared with those without IAC, patients with IAC had a higher risk of stroke occurrence (adjusted OR 1.62, 95% CI 1.18-2.23, P = 0.001) and stroke recurrence (adjusted OR 1.77, 95% CI 1.25-2.51, P = 0.003). However, we did not find a significant correlation between IAC and post-stroke mortality (pooled OR 1.12, 95% CI 0.80-1.56, P = 0.504). CONCLUSIONS: Our meta-analysis demonstrated that the presence of IAC was identified as an independent risk factor for ischemic stroke occurrence and recurrence but is not a predictor of post-stroke mortality.

MicroRNA-30a-5p Promotes Chronic Heart Failure in Rats by Targeting Sirtuin-1 to Activate the Nuclear Factor-κB/NOD-Like Receptor 3 Signaling Pathway.

OBJECTIVE: MicroRNA-30a-5p (miR-30a-5p) has been identified as a marker of heart failure; however, its functional mechanisms in chronic heart failure (CHF) remain unknown. We aim to investigate the role of miR-30a-5p targeting sirtuin-1 (SIRT1) in myocardial remodeling in CHF via the nuclear factor-κB/NOD-like receptor 3 (NF-κB/NLRP3) signaling pathway. METHODS: CHF rat models were established using aortic coarctation. The expression of miR-30a-5p, SIRT1, and the NF-κB/NLRP3 signaling pathway-related factors in CHF rats was determined. The CHF rats were then respectively treated with altered miR-30a-5p or SIRT1 to explore their roles in cardiac function, myocardial function, inflammatory response, pathological changes, and cardiomyocyte apoptosis. The binding relation between miR-30a-5p and SIRT1 was confirmed. RESULTS: MiR-30a-5p was upregulated whereas SIRT1 was downregulated in myocardial tissues of CHF rats. MiR-30a-5p inhibition or SIRT1 overexpression improved cardiac and myocardial function, and suppressed the inflammatory response, alleviated pathological changes and inhibited cardiomyocyte apoptosis in CHF rats. MiR-30a-5p targeted SIRT1 to regulate the NF-κB/NLRP3 signaling pathway. In CHF rats, downregulated miR-30a-5p and silenced SIRT1 could reverse the beneficial effects of downregulated miR-30a-5p. CONCLUSION: Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway.

[Advances in cell nuclear mechanobiology and its regulation mechanisms].

As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.

A Semiconductor-Mediator-Catalyst Artificial Photosynthetic System for Photoelectrochemical Water Oxidation.

In fabricating an artificial photosynthesis (AP) electrode for water oxidation, we have devised a semiconductor-mediator-catalyst structure that mimics photosystem II (PSII). It is based on a surface layer of vertically grown nanorods of Fe2 O3 on fluorine doped tin oxide (FTO) electrodes with a carbazole mediator base and a Ru(II) carbene complex on a nanolayer of TiO2 as a water oxidation co-catalyst. The resulting hybrid assembly, FTO|Fe2 O3 |-carbazole|TiO2 |-Ru(carbene), demonstrates an enhanced photoelectrochemical (PEC) water oxidation performance compared to an electrode without the added carbaozle base with an increase in photocurrent density of 2.2-fold at 0.95 V vs. NHE and a negatively shifted onset potential of 500 mV. The enhanced PEC performance is attributable to carbazole mediator accelerated interfacial hole transfer from Fe2 O3 to the Ru(II) carbene co-catalyst, with an improved effective surface area for the water oxidation reaction and reduced charge transfer resistance.

Notch-1 signaling promotes reattachment of suspended cancer cells by cdc42-dependent microtentacles formation.

Circulating tumor cells (CTCs) are associated with a higher risk of metastasis in tumor patients. The adhesion and arrest of CTCs at a secondary site is an essential prerequisite for the occurrence of tumor metastasis. CTC reattachment has shown to be dependent on microtentacle (McTN) formation in vivo. However, the specific molecular mechanism of McTN formation in suspended cancer cells remains largely unclear. Here, we demonstrated that the activation of Notch-1 signaling triggers McTN formation to facilitate cell reattachment in suspended cell culture conditions. Moreover, molecular mechanistic studies revealed that McTN formation is governed by the balance between microtubule-driven outgrowth and actomyosin-driven cell contractility. The activation of Notch-1 downregulates the acetylation level of microtubules via the Cdc42/HDAC6 pathway, which contributes to microtubule polymerization. Simultaneously, Notch-1 signaling-induced Cdc42 activation also reduced phosphorylation of myosin regulatory light chain, leading to cell contractility attenuation. Altogether, these results defined a novel mechanism by which Notch-1 signaling disturbs the balance between the expansion of microtubules and contraction of the cortical actin, which promotes McTN formation and cell reattachment. Our findings provide a new perspective on the effective therapeutic target to prevent CTC reattachment.

Association of Plaque Features with Infarct Patterns in Patients with Acutely Symptomatic Middle Cerebral Artery Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns. METHODS: A single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model. RESULTS: Of 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016). CONCLUSIONS: Increased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis.

Effects of Glycosylation and d-Amino Acid Substitution on the Antitumor and Antibacterial Activities of Bee Venom Peptide HYL.

Glycosylation is a promising strategy for modulating the physicochemical properties of peptides. However, the influence of glycosylation on the biological activities of peptides remains unknown. Here, we chose the bee venom peptide HYL as a model peptide and 12 different monosaccharides as model sugars to study the effects of glycosylation site, number, and monosaccharide structure on the biochemical properties, activities, and cellular selectivities of HYL derivatives. Some analogues of HYL showed improvement not only in cell selectivity and proteolytic stability but also in antitumor and antimicrobial activity. Moreover, we found that the helicity of glycopeptides can affect its antitumor activity and proteolytic stability, and the α-linked d-monosaccharides can effectively improve the antitumor activity of HYL. Therefore, it is possible to design peptides with improved properties by varying the number, structure, and position of monosaccharides. What's more, the glycopeptides HYL-31 and HYL-33 show a promising prospect for antitumor and antimicrobial drugs development, respectively. In addition, we found that the d-lysine substitution strategy can significantly improve the proteolytic stability of HYL. Our new approach provides a reference or guidance for the research of novel antitumor and antimicrobial peptide drugs.

Separation method of bending and torsion in shape sensing based on FBG sensors array.

This paper presents a theoretical method for separating bending and torsion of shape sensing sensor to improve sensing accuracy during its deformation. We design a kind of shape sensing sensor by encapsulating three fibers on the surface of a flexible rod and forming a triangular FBG sensors array. According to the configuration of FBG sensors array, we derive the relationship between bending curvature and bending strain, and set up a function about the packaging angle of FBG sensor and strain induced by torsion under different twist angles. Combined with the influence of bending and torsion on strain, we establish a nonlinear matrix equation resolving three unknown parameters including maximum strain, bending direction and wavelength shift induced by torsion and temperature. The three parameters are sufficient to separate bending and torsion, and acquire two scalar functions including curvature and torsion, which could describe 3D shape of rod according to Frenet-Serret formulas. Experimental results show that the relative average error of measurement about maximum strain, bending direction is respectively 2.65% and 0.86% when shape-sensing sensor is bent into an arc with a radius of 260 mm. The separating method also applied to 2D shape and 3D shape of reconstruction, and the absolute spatial position maximum error is respectively 3.79mm and 11.10mm when shape-sensing sensor with length 500mm is bent into arc shape with a radius 260mm and helical curve. The experiment results verify the feasibility of separating method, which would provide effective parameters for precise 3D reconstruction model of shape sensing sensor.

Interface and surface engineering of hematite photoanode for efficient solar water oxidation.

Engineering the interface and surface structures of semiconductor-based photoelectrodes for improved charge transfer dynamics and promoted water redox reaction kinetics is essential to achieve efficient photoelectrochemical (PEC) water splitting. In this work, α-Fe2O3 nanorods, successively coated with TiO2 and CoOx thin layers, were reported as the photoanode for solar-driven water oxidation. The obtained α-Fe2O3/TiO2/CoOx photoanode exhibits superior PEC performance as compared to bare α-Fe2O3, with a 3.3-time improvement in photocurrent density at 1.23 V vs reversible hydrogen electrode. This significant enhancement results from the formed heterojunction between α-Fe2O3 and TiO2 for the accelerated photogenerated charge separation and transfer as well as the passivated surface defects by the TiO2 overlayer for reduced charge recombination. Additionally, the existence of CoOx as the oxygen evolution catalyst significantly facilitates the surface reaction kinetics and thus reduces the overpotential for water oxidation. This study demonstrates a collaborative strategy of interface and surface engineering to design novel structures of α-Fe2O3 based photoanodes for highly efficient solar water oxidation.

A blended intervention to promote physical activity, health and work productivity among office employees using intervention mapping: a study protocol for a cluster-randomized controlled trial.

BACKGROUND: Regular participation in moderate-to-vigorous physical activity (MVPA) is related to decreased risk of morbidity and mortality. Among working populations, lack of MVPA may also be a risk factor for absenteeism and presenteeism. Both traditional workplace-based and web-based interventions have been suggested as being effective in promoting participation MVPA, health-related outcomes, and work-related productivity. However, several challenges limit their application in real world contexts. A 'blended' intervention approach combining the two intervention strategies is proposed to overcome these limitations. The proposed intervention aims to utilize the blended approach to increase participation in MVPA, health-related outcomes, and work productivity among inactive workers. METHODS: The study will comprise of a three-group cluster randomized controlled trial (cluster-RCT), comprising a three-month actual intervention and a nine-month behavioral follow-up period. The three groups will be: a web-based intervention group, a blended intervention group combining the web-based components with face-to-face workshops and posters, and a control group. Physically inactive office employees (N = 495) from 33 companies (i.e., clusters) will be recruited and randomly assigned to the three groups by cluster randomization. The intervention mapping (IM) framework will be used for selecting and applying effective health behavioral theories and behavioral change techniques (BCTs) to the development, implementation and assessment of the intervention, which will be personally tailored. The primary outcome variable will be objectively-measured MVPA using an accelerometer. Secondary outcomes will consist of indices of health including adiposity, blood pressure, blood sugar, blood lipids, self-reported depression, anxiety, stress, health-related quality of life and work-related variables including absenteeism and presenteeism. DISCUSSION: The proposed study adopts a robust blended intervention approach that is expected to overcome challenges in applying workplace-based and web-based interventions separately and yield larger effects in promoting MVPA participation, health-related outcomes and work productivity. Improvements in work productivity outcomes will be of particular interest to employers. If more effective, the new blended intervention has the potential to be implemented on a larger scale to benefit workplace populations. TRIAL REGISTRATION: The trial is prospectively registered at the ClinicalTrials.gov PRS (Trial ID: NCT04391270; Date of First Posted: May 18, 2020).

Inflammation-regulatory microRNAs: Valuable targets for intracranial atherosclerosis.

Intracranial atherosclerosis (ICAS) is the most common etiology of ischemic stroke with the highest rate of stroke recurrence. Little is currently known of the association of circulating inflammation-regulatory microRNAs (miRNAs) with ICAS. In this review, we briefly discuss that ICAS is characterized as a dynamic and unstable inflammatory process within intracranial arteries. Then, as a topic of discussion, we mainly concentrate on the following crucial miRNAs (miR-155, miR-27a/b, miR-342-5p, miR-21, miR-124, and miR-223) by virtue of their multiple roles in regulating the progression of atherosclerosis involved with systemic and local inflammatory activities in cerebral arteries. Clinical perspectives of other miRNAs (miR-146a, miR-181b, miR-126, miR-143, and let-7b) in ICAS are also mentioned. In relevance to the inflammatory mechanisms of ICAS, the in-depth knowledge of miRNAs engaged in the progression of intracranial atherosclerotic plaques may provide an approach to a more precise exploration of diagnostic and therapeutic targets for ICAS.

Postmortem Study Exploring Distribution and Patterns of Intracranial Artery Calcification.

Background and Purpose- Intracranial artery calcification detected by computed tomography is associated with ischemic stroke as an indicator of intracranial atherosclerosis. However, little is known about its histopathology. This study aimed to explore the intracranial calcification patterns and their associations with atherosclerotic plaques. Methods- We recruited 32 adult autopsy cases to assess the calcification patterns and distributions in the middle cerebral artery, vertebral artery, and basilar artery. The relationships of calcification patterns with plaque phenotype and luminal stenosis were evaluated. The calcification patterns on computed tomography were correlated with that on histology. Results- Visible calcifications were detected within 37 (39%) segments, including 25 segments with intimal calcification, 6 segments with internal elastic lamina calcification, 3 segments with adventitial calcification, and 3 segments with concurrent calcification. Calcification occurred more often in the vertebral artery (51%), followed by the middle cerebral artery (35%) and basilar artery (14%; P<0.01 for vertebral artery versus basilar artery). Internal elastic lamina calcification was predominantly detected in the vertebral artery (7/8, 88%). All of the 27 (100%) intimal calcifications were present in the progressive atherosclerotic lesions ( P<0.001), whereas only 3/8 (38%) internal elastic lamina calcifications and 4/6 (67%) adventitial calcifications were associated with progressive plaques. Arteries with intimal calcification had more severe luminal stenosis than those without (46% versus 21%; P<0.001). Conclusions- Our histological findings indicate that the presence of intracranial artery calcification has 3 patterns, including intimal, internal elastic lamina, and adventitial calcifications. But only intimal calcification is related with progressive atherosclerotic lesions, indicative of a proxy for intracranial atherosclerosis.

Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome. METHODS: In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6). RESULTS: Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P=0.027). CONCLUSIONS: Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.

Impact of intracranial artery calcification on cerebral hemodynamic changes.

PURPOSE: Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries. METHODS: Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA). RESULTS: In total, 318 patients were analyzed. Spearman's correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p < 0.001 individually. Similar correlation was also found between IAC Agatston score and high VBA velocity/high VBA PI, p ≤ 0.001 individually. Multiple logistic regression analysis showed IAC Agatston score was an independent risk factor for high MCA velocity (OR 1.533; 95% CI 1.235-1.903), high VBA velocity (OR 1.964; 95% CI 1.381-2.794), and high VBA PI (OR 1.200; 95% CI 1.016-1.418), respectively. CONCLUSION: Heavier IAC might cause generalized artery flow velocity changes and increased pulsatility index, which may indicate high resistance within cerebrovasculature.