Exploring consumer responses to official endorsement: roles of credibility and attractiveness attributes in live streaming.

Introduction: Official endorsement, distinct from celebrity, expertise, and peer endorsement, introduces a new paradigm where local government officials use online platforms, particularly live streaming, to promote local products and brands. Methods: This study examines the influence of official endorsement on consumer responses using the source credibility and source attractiveness models. We developed a framework that considers official credibility and attractiveness attributes as antecedents, and consumer perceived security and enjoyment as mediators, affecting purchase intention and local brand awareness. The study also incorporates variables such as consumer region and power distance belief. Results: Data from 594 responses obtained through an online survey were analyzed using structural equation modeling. The results indicate that official credibility attributes (expertise, trustworthiness, government credibility) enhances consumer perceived security, while official attractiveness attributes (physical attractiveness, interaction friendliness, and similarity with consumers) increases consumer enjoyment. Both perceived security and enjoyment positively influence purchase intention and local brand awareness. These relationships are partially moderated by consumer region and power distance belief. Discussion: This research pioneers the study of official endorsements, expanding the endorsement literature. It also provides practical insights for marketing professionals and government officials on leveraging official endorsements to enhance the value of local products and brands..

METTL3 Regulates Osteoclast Biological Behaviors via iNOS/NO-Mediated Mitochondrial Dysfunction in Inflammatory Conditions.

Excessive differentiation of osteoclasts contributes to the disruption of bone homeostasis in inflammatory bone diseases. Methyltransferase-like 3 (METTL3), the core methyltransferase that installs an N6-methyladenosine (m6A) modification on RNA, has been reported to participate in bone pathophysiology. However, whether METTL3-mediated m6A affects osteoclast differentiation in inflammatory conditions remains unelucidated. In this study, we observed that the total m6A content and METTL3 expression decreased during LPS-induced osteoclastogenesis. After knocking down METTL3, we found reduced levels of the number of osteoclasts, osteoclast-related gene expression and bone resorption area. A METTL3 deficiency increased osteoclast apoptosis and pro-apoptotic protein expression. RNA sequencing analysis showed that differentially expressed genes in METTL3-deficient cells were mainly associated with the mitochondrial function. The expression of the mitochondrial function-related genes, ATP production and mitochondrial membrane potential decreased after METTL3 knockdown. Moreover, the most obviously upregulated gene in RNA-Seq was Nos2, which encoded the iNOS protein to induce nitric oxide (NO) synthesis. METTL3 knockdown increased the levels of Nos2 mRNA, iNOS protein and NO content. NOS inhibitor L-NAME rescued the inhibited mitochondrial function and osteoclast formation while suppressing osteoclast apoptosis in METTL3-silenced cells. Mechanistically, a METTL3 deficiency promoted the stability and expression of Nos2 mRNA, and similar results were observed after m6A-binding protein YTHDF1 knockdown. Further in vivo evidence revealed that METTL3 knockdown attenuated the inflammatory osteolysis of the murine calvaria and suppressed osteoclast formation. In conclusion, these data suggested that METTL3 knockdown exacerbated iNOS/NO-mediated mitochondrial dysfunction by promoting a Nos2 mRNA stability in a YTHDF1-dependent manner and further inhibited osteoclast differentiation and increased osteoclast apoptosis in inflammatory conditions.

Inhibition of miR-141-3p attenuates apoptosis of neural stem cells via targeting PBX1 to regulate PROK2 transcription in MCAO mice.

MicroRNA-141-3p (miR-141-3p) has been found to be altered in the brain following a stroke. Herein, we investigate the impact of miR-141-3p on the apoptosis of neural stem cells (NSCs) in mice with middle cerebral artery occlusion (MCAO) and the potential mechanisms involved. Eight-week-old mice were injected intracerebroventricularly with miR-141-3p, antagomir-141-3p, or agomir negative control 2 h before MCAO, and animal behavior tests and infraction volume measurements were performed 24 h later. MCAO-mediated brain injury and NSCs apoptosis were observed by H&E, TTC, and TUNEL staining. The expression of cleaved caspase-3 and Ki67 was detected by western blotting. The luciferase reporter assay proved that miR-141-3p in combination with its target gene PBX homeobox 1 (PBX1). Exogenous miR-141-3p (agomir-141-3p) treatment increased infraction volume and brain edema and damaged neurological functions compared to control mice. Agomir-141-3p increased miR-141-3p expression in brain tissue of mice with MCAO and suppressed PBX1 expression. The effects of the agomir-141-3p-induced apoptosis in NSCs treated with oxygen-glucose deprivation (OGD)/reoxygenation (R) were abolished by PBX1 overexpression. The results from UCSC and JASPAR database showed that prokineticin 2 (PROK2) was a transcription factor of PBX1. The expression of PROK2 was transcriptionally regulated by PBX1 using RT-PCR and western blot assays. The effects of the apoptosis-promoting caused by PBX1 inhibition in NSCs treated with OGD/R were reversed by PROK2 inhibition. In conclusion, the miR-141-3p/PBX1/PROK2 axis might be a novel therapeutic target for the apoptosis of NSCs in MCAO.

rs2253820 Variant Controls Blood Pressure Dip After Stroke by Increasing CLOCK-BMAL1 Expression.

Circadian rhythm (CR) disturbances are associated with the development of cardiovascular diseases, including stroke. The central clock in the brain, which is maintained by circadian genes, maintains the daily rhythm according to the external environment. Here, we aimed to probe the interaction between the PER1rs2253820 variant and blood pressure dip (BPD) status and mechanisms. We studied spontaneously hypertensive rats (SHR) with transient middle cerebral artery occlusion (SHR-tMCAO). The mutation site of PER1 was identified using bioinformatics analysis, followed by RT-qPCR and western blot validation. SHR-tMCAO showed increased brain infarct volume associated with CR. CK1, BMAL1, and CLOCK proteins oscillated synchronously in SHR-tMCAO, whereas PER1 showed rhythm disturbances. CK1, CLOCK, and BMAL1 levels first elevated and then slowly decreased after ischemia, whereas PER1 level continued to decrease. CLOCK and PER1 are co-localized in the suprachiasmatic nucleus of the hypothalamus. rs2253820 accelerates PER1 phosphorylation via CK1. The rs2253820 knockdown attenuated CR disturbances, reduced PER1 phosphorylation in SHR and inhibited the transcription of BMAL1 and CLOCK. CK1 suppression attenuated the degradation of PER1 phosphorylation and reduced neuronal damage. Overall, rs2253820 accelerated PER1v phosphorylation via CK1, leading to PER1 degradation, BMAL1 and CLOCK1 transcription, and BPD exacerbation.

Does Brand Truth-Telling Yield Customer Participation? The Interaction Effects of CSR Strategy and Transparency Signaling.

Customer participation in brand environmental responsibility is necessary for enterprises and consumers to co-create value. However, it is not yet clear why some corporate social responsibility (CSR) communications are more effective in attracting higher customer participation in a digitally transparent environment. Based on signal theory and social identity theory, this study examines the impact of the interactive effect of CSR strategy (proactive vs. reactive) and transparency signals (high vs. low) on customer trust (perceived integrity and perceived competence), customer-brand identification, and participation intention in brand environmental responsibility. We conduct a 2 × 2 study with 140 respondents. The findings reveal a significant interaction effect of CSR strategy and transparency signals on perceived integrity, perceived competence, and participation intention in brand environmental responsibility. Mediation analysis reveals that the impact of CSR strategy on participation intention is serially mediated via perceived trust and customer-brand identification and varies across different transparency levels.

YTHDF1 regulates endoplasmic reticulum stress, NF-κB, MAPK and PI3K-AKT signaling pathways in inflammatory osteoclastogenesis.

Abnormal increases in osteoclast differentiation and activity contribute to excessive bone resorption in inflammatory bone diseases. The specific m6A-binding protein YT521-B homology domain family 1 (YTHDF1) participates in many physiopathological processes by regulating mRNA stability or translation. However, whether YTHDF1 is involved in the regulation of inflammatory osteoclastogenesis remains a mystery. This study revealed that YTHDF1 expression was upregulated during lipopolysaccharide (LPS)-stimulated osteoclast differentiation. Knockdown of Ythdf1 inhibited osteoclast formation, bone resorption and the expression of osteoclast-related genes (Tnfrsf11a, Traf6, Mmp9 and Acp5). Analysis of RNA sequencing data showed that the genes downregulated by Ythdf1 knockdown were closely associated with endoplasmic reticulum (ER) stress and osteoclast differentiation. Western blotting confirmed that Ythdf1 depletion suppressed activation of the ER stress-related PERK, IRE1α and ATF6 signaling pathways. The ER stress activator tunicamycin (Tm) partially rescued the decreased expression of Mmp9 and Acp5 caused by Ythdf1 deficiency. Meanwhile, Ythdf1 depletion inhibited the phosphorylation levels of key proteins in the NF-κB, MAPK and PI3K-AKT signaling pathways and decreased the mRNA stability of Tnfrsf11a, which is the major upstream signaling molecule that mediates the activation of these pathways during osteoclast differentiation. In conclusion, our findings suggest that Ythdf1 knockdown inhibits inflammatory osteoclast differentiation and function by suppressing ER stress signaling pathways. Ythdf1 knockdown also inactivates the signaling pathways involved in osteoclast differentiation by inhibiting Tnfrsf11a mRNA stability. These findings will help shed light on the molecular mechanisms of m6A-mediated epigenetic regulation in inflammatory osteoclastogenesis.

Association between the ratio of serum eicosapentaenoic acid to arachidonic acid and risk of coronary artery disease in young Chinese patients.

Objective: Long-chain (LC) omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may play an anti-inflammatory effect and decrease the risk of coronary artery disease (CAD). In contrast, omega-6 PUFA, mainly arachidonic acid (AA), has pro-inflammatory and pro-aggregatory effects, which may increase the risk of CAD. This study evaluated the associations between EPA, DHA, AA, and their ratios (EPA/AA and DHA/AA) with the risk of CAD in young Chinese patients. Methods: A total of 182 young patients with CAD and 143 age-matched controls were included. Traditional cardiovascular risk factors were recorded. Serum EPA, DHA and AA were measured by ultra-performance liquid chromatography-mass spectrometry. Results: The level of AA was significantly higher, while the level of EPA was lower in the CAD group than that in the control group. There was no significant difference in DHA level in the two groups. Both the ratios of EPA/AA and DHA/AA were lower in the CAD group than that in the control. Multivariate logistic regression analysis showed that higher serum AA level was associated with the increased risk of CAD, while EPA was a protective factor for CAD. There was no significant association between DHA level and the risk of CAD. Although both higher ratios of EPA/AA [per tertile increment, adjusted odds ratios (ORs) (OR) 0.356, 95% confidence intervals (CI) 0.247-0.513] and DHA/AA (adjusted OR = 0.465, 95%CI = 0.332-0.653) were associated with a lower risk of CAD in young patients. Receiver operating characteristic (ROC) curve analysis showed that compared with AA, the diagnostic value was increased in EPA/AA, but not in DHA/AA. Conclusion: EPA, but not DHA may play a protective role in CAD, while AA may be associated with the increased risk of CAD in young Chinese patients. The ratio of EPA/AA can increase the predictive value for diagnosing CAD than EPA or AA alone.

Value acquisition, value co-creation: The impact of perceived organic grocerant value on customer engagement behavior through brand trust.

Affected by COVID-19, there is a growing trend toward healthy lifestyles and organic food consumption. The literature on organic foods focuses on the factors that influence buying behavior. A thriving organic business requires both sustained consumption and consumer contributions beyond the purchase-customer engagement behavior. The purpose of this study is to examine the factors that may drive member customers to engage with organic grocerants. This study surveyed 280 Chinese member customers of an organic grocerant to explore how to drive customer engagement behavior. Based on value co-creation theory and the customer engagement literature, this study proposed a "value acquisition-value co-creation" framework to explore the relationship between perceived value, brand trust, and customer engagement behavior. The results show that emotional and social value can directly and effectively motivate customer engagement behavior in organic grocerants. However, consumers' perceived quality value and price value will not directly affect customer engagement behavior but instead indirectly affect it through brand trust. Furthermore, improving the perceived value of emotion, quality and price can strengthen brand trust in organic grocerants. The study confirms that brand trust is critical to organic grocerant and customer engagement. Our findings provide a new perspective for understanding the relationship between the value customers receive from organic food consumption and value co-creation through customer engagement behavior.

Red blood cell distribution width in different time-points of peripheral thrombolysis period in acute ischemic stroke is associated with prognosis.

The relationship between red blood cell distribution width (RDW) in peripheral thrombolysis period and prognosis is not fully clarified in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Our study aimed to clarify this issue. A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database was done and followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between RDW levels at various time-points after IVT and the occurrence risk of hemorrhagic transformation (HT) and recurrent stroke, and used COX regression to assess the hazard ratios of outcomes with RDW levels. Elevated risk of HT was found in higher tertiles of RDW (OR = 10.282, 95% confidence interval (CI) 2.841-39.209, P < 0.001 in Tp tertile G3; OR = 5.650, 95% CI 1.992-16.025, P = 0.001 in T24 tertile G3; OR = 4.308, 95% CI 1.480-12.542, P = 0.007 in T48 tertile G3 and OR = 6.384, 95% CI 2.201-18.515, P = 0.001 in T72 tertile G3, respectively). Occurrence of recurrent stroke was highest in the RDW tertile G3 (HR = 4.580, 95% CI 2.123-9.883, P < 0.001 in Tp tertile G3; HR = 5.731, 95% CI 2.498-13.151, P = 0.001 in T24 tertile G3; HR = 3.019, 95% CI 1.969-4.059, P = 0.031 in T48 tertile G3; HR = 3.318, 95% CI 1.598-6.890, P = 0.001 in T72 tertile G3, respectively). Mean RDW levels ≥13.60 among AIS patients undergoing thrombolysis was associated with higher risk of HT and recurrent stroke.

Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson's Disease Patients.

This study aimed to investigate the effect of berberine hydrochloride on the diversity of intestinal flora in patients with Parkinson's disease (PD). Prospectively selected 68 PD patients, admitted to our hospital from April 2021 to June 2021, were randomly assigned to an observation group and a control group (n = 34 per group). Patients in the control group were given conventional treatment in accordance with Parkinson's diagnosis and treatment guidelines. Patients in the observation group were administered berberine hydrochloride besides the treatment in the control group. After continuous treatment for 3 months, the enzyme-linked immunosorbent assay was applied to determine interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. High-throughput sequencing technology was employed to perform DNA sequencing on the 16S rRNA genes of all bacteria in stool samples before and after treatment in the two groups to analyze the distribution of intestinal flora. After treatment, the levels of IL-8, IL-6, and TNF-α were lower in the observation group than those in the control group (P < 0.05). Regarding intestinal flora, the Chao index, Ace index, and Shannon index were higher in the observation group than those in the control group. The Simpson index was lower in the observation group than that of the control group (P < 0.05). The principal component analysis chart analysis exhibited that the overall structure of the intestinal flora was quite different between the observation and the control groups after treatment. Berberine hydrochloride can improve the disorder of intestinal flora in PD patients and suppress the expression of inflammatory factors.

Blood Pressure Rhythm and Blood Pressure Variability as Risk Factors for White Matter Lesions: A Cross-Sectional Study.

BACKGROUND White matter lesions are common in the elderly. The aim of this study was to explore the correlation between blood pressure rhythm and blood pressure variability with white matter lesions. MATERIAL AND METHODS A total of 144 subjects aged 40 to 80 years underwent MRI scanning to assess the degree of white matter lesions using the Fazekas scale. The regional cerebral blood flow was detected by brain perfusion imaging, and an ambulatory blood pressure monitor was used to measure the circadian blood pressure rhythm. Odds ratio and the 95% confidence interval was computed using logistics regression analysis. The relationship between various factors and blood pressure was calculated by curve simulation. RESULTS With the increase of white matter lesions, the regional cerebral blood flow at the lesion decreased gradually. Systolic blood pressure day/night difference ratio (OR=0.815, 95% CI 0.729-0.910), diastolic blood pressure day/night difference ratio (OR=0.895, 95% CI 0.831-0.964), systolic blood pressure coefficient of variation (OR=1.589, 95% CI 1.273-1.983), and diastolic blood pressure coefficient of variation (OR=1.363, 95% CI 1.150-1.616) were significantly associated with Fazekas score (P<0.05 for all). CONCLUSIONS Greater blood pressure variability and blood pressure rhythm disorders were associated with lower regional cerebral blood flow in patients with white matter lesions.

Blood pressure undulation of peripheral thrombolysis period in acute ischemic stroke is associated with prognosis.

BACKGROUND: Evidence suggests that patients with higher blood pressure variability (BPV) have a higher risk for stroke but the relationship between BPV and stroke outcomes is unknown in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). The objective of this study is to investigate the association among BPV, BP values and stroke outcomes. METHODS: A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database were done. Then, these patients were followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between mean BP values, BPV and the risk of stroke outcomes from prior IVT to 72 h after IVT. Meanwhile, we also used COX regression to assess the hazard ratios of stroke outcomes with BPV within 3 months. Furthermore, we tested the effect of BP level at various time-points (prior to IVT and at 0, 2, 4, 8, 12, 24, 48 and 72 h after IVT) on development of postthrombolytic stroke outcomes. RESULTS: Higher BPV from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months [SBPV of recurrent stroke: odds ratios (OR) = 5.298, 95% confidence interval (CI) 1.339-10.968, P = 0.018; DBPV of recurrent stroke: OR = 6.397, 95% CI 1.576-25.958, P = 0.009, respectively]. In addition, patients with recurrent stroke had significantly higher mean SBP (OR=1.037, 95% CI 1.006-1.069, P = 0.019). Furthermore, higher BP at different time points were associated with greater risk of recurrent stroke from prior IVT to 72 h after IVT. CONCLUSION: Higher BPV and SBP from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months.

Focus on blood pressure levels and variability in the early phase of acute ischemic stroke with hypertension and carotid stenosis.

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single-center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140-159 mm Hg and or DBP: 90-99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes (recurrent stroke, all-cause death and the composite cardiovascular events) at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.

AKR1C3 and Its Transcription Factor HOXB4 Are Promising Diagnostic Biomarkers for Acute Myocardial Infarction.

Background: A recent study disclosed that ferroptosis was an important myocyte death style in myocardial infarction (MI). However, the diagnostic value of ferroptosis regulators and correlated underlying mechanisms in acute myocardial infarction (AMI) remain unknown. Methods: Bioinformatical analyses were conducted to identify the candidate biomarkers for AMI, and the collected local samples were used to validate the findings via real-time quantitative PCR. Bioinformatical analysis and luciferase reporter assay were implemented to identify the transcriptional factor. Transient transfection and ferroptosis characteristic measurement, including glutathione peroxidase 4, malondialdehyde, iron, and glutathione, was performed to verify the ability of the candidate gene to regulate the ferroptosis of cardiomyocytes. A meta-analysis was conducted in multiple independent cohorts to clarify the diagnostic value. Results: A total of 121 ferroptosis regulators were extracted from previous studies, and aldo-keto reductase family 1 member C3 (AKR1C3) was significantly downregulated in the peripheral blood samples of AMI cases from the analysis of GSE48060 and GSE97320. HOXB4 served as a transcriptional activator for AKR1C3 and could suppress the ferroptosis of the H9C2 cells treated with erastin. Besides this, peripheral blood samples from 16 AMI patients and 16 patients without coronary atherosclerotic disease were collected, where AKR1C3 and HOXB4 both showed a high diagnostic ability. Furthermore, a nomogram including HOXB4 and AKR1C3 was established and successfully validated in six independent datasets. A clinical correlation analysis displayed that AKR1C3 and HOXB4 were correlated with smoking, CK, CK-MB, and N-terminal-pro-B-type natriuretic peptide. Conclusion: Taken together, this study demonstrates that AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of AMI.

Circ_0062166 aggravates cerebral ischemia-reperfusion injury through targeting miR-526b-5p/BCL2L13 axis.

BACKGROUND: Cerebral ischemia-reperfusion (CIR) injury is a severe disease, which may cause serious dysfunction of the brain. Most circular RNAs (circRNAs) have been demonstrated to play a significant role in CIR injury. However, a novel circRNA, circ_0062166 (circ_BCL2L13) has not been investigated for CIR injury. Hence, we aim to disclose the role of circ_0062166 in CIR injury in this study. METHODS: Firstly, RT-qPCR was applied to examine the expression of circ_0062166 in oxygen-glucose deprivation and reoxygenation (OGD/R) cell model. Functional assays were conducted to detect the role of circ_0062166 in CIR injury. RNA pull down, RIP and luciferase reporter assays were implemented to probe into the regulatory mechanism of circ_0062166. RESULTS: Circ_0062166 was significantly up-regulated in neuro-2A (N2A) neuroblastoma cells following OGD/R. Functionally, the silencing of circ_0062166 inhibited cell proliferation and promoted cell apoptosis under OGD/R condition. From the perspective of mechanism, circ_0062166 functioned as a competing endogenous RNA (ceRNA) for microRNA-526b-5p (miR-526b-5p) and regulated BCL2 like 13 (BCL2L13). Eventually, the promoting role of the circ_0062166/miR-526b-5p/BCL2L13 axis in the CIR injury was verified. CONCLUSION: To sum up, the present study has demonstrated that circ_0062166/miR-526b-5p/BCL2L13 axis accelerated the progression of CIR injury, which might provide effective strategies for CIR injury therapy.

Association of Blood Pressure, White Matter Lesions, and Regional Cerebral Blood Flow.

BACKGROUND At present, the association between blood pressure, regional cerebral blood flow, and white matter lesions is not well understood. MATERIAL AND METHODS A total of 147 subjects aged from 40 to 80 years were assessed by the Fazekas score for white matter lesions, CT perfusion imaging for regional cerebral blood flow, and 24-h ambulatory blood pressure monitoring for blood pressure level and rhythm. Logistic regression analysis was used to obtain the odds ratio and 95% confidence interval between Fazekas scores and relevant factors. The relationship between blood pressure index and regional cerebral blood flow was analyzed through cubic curve estimation. RESULTS Fazekas score was negatively correlated with regional cerebral blood flow (r=-0.801; r=-0.831, P<0.001). For subcortical lesion, the regional cerebral blood flow of Fazekas grade 0 was 1.976 times that of Fazekas grade 3 (OR=1.976, 95% CI=1.576-2.477), and for periventricular lesion, the regional cerebral blood flow of Fazekas grade 0 was 2.034 times that of Fazekas grade 3 (OR=2.034, 95% CI=1.602-2.583). Increased nighttime systolic blood pressure may be more dangerous (OR=1.112, 95% CI=1.059-1.169). The day-night systolic blood pressure ratio (OR=0.801, 95% CI 0.711-0.902) and the day-night diastolic blood pressure ratio (OR=0.876, 95% CI 0.807-0.950) were significantly correlated with Fazekas score. CONCLUSIONS The decrease of white matter regional cerebral blood flow caused by hypertension is probably one of the important causes of white matter lesions. Patients with white matter lesions should also pay attention to the rhythm of blood pressure when controlling hypertension, especially if their blood pressure is too high or too low at night.

YTHDF2 mediates LPS-induced osteoclastogenesis and inflammatory response via the NF-κB and MAPK signaling pathways.

Aberrant elevation of osteoclast differentiation and function is responsible for disrupting bone homeostasis in various inflammatory bone diseases. YTH domain family 2 (YTHDF2) is a well-known m6A-binding protein that plays an essential role in regulating cell differentiation and inflammatory processes by mediating mRNA degradation. However, the regulatory role of YTHDF2 in inflammatory osteoclast differentiation remains unelucidated. Here, we detected the expression of m6A-related genes and found that YTHDF2 was upregulated in RANKL-primed osteoclast precursors stimulated with lipopolysaccharide (LPS). Ythdf2 knockdown in RAW264.7 cells and primary bone marrow-derived macrophages (BMMs) enhanced osteoclast formation and bone resorption, which was assessed by TRAP staining assay and pit formation assay. Ythdf2 depletion upregulated osteoclast-related gene expression and proinflammatory cytokine secretion. In contrast, overexpression of Ythdf2 produced the reverse effect. Furthermore, Ythdf2 knockdown enhanced the phosphorylation of IKKα/ß, IκBα, ERK, P38 and JNK. NF-κB and MAPK signaling pathway inhibitors effectively abrogated the enhanced expression of Nfact1, c-Fos, IL-1ß and TNF-α caused by Ythdf2 knockdown. Mechanistically, the mRNA stability assay revealed that Ythdf2 depletion led to stabilization of Tnfrsf11a, Traf6, Map4k4, Map2k3, Map2k4 and Nfatc1 mRNA. In summary, our findings demonstrated that YTHDF2 has a negative regulatory role in LPS-induced osteoclast differentiation and the inflammatory response via the NF-κB and MAPK signaling pathways.

Optimal blood pressure levels in different phases of peripheral thrombolysis period in acute ischemic stroke.

BACKGROUND: Dramatic changes of blood pressure (BP) were observed in the peripheral thrombolysis period, however, there is no consensus about BP control targets in the different phases. METHODS: We retrospectively studied a consecutive sample of 510 patients treated with intravenous thrombolysis and followed-up for 3 months. The peripheral thrombolysis period was divided into these phases: Phase 1 (from onset to thrombolysis), Phase 2 (thrombolysis), Phase 3 (from thrombolysis to 24 h after thrombolysis), and Phase 4 (from 24 h to 7 days after thrombolysis). Patients were divided into quintiles according to mean blood pressure in these phases, respectively. Neurological improvement was evaluated using the modified Rankin Scale score at 3-month after thrombolysis. RESULTS: Lower risk of intracerebral hemorrhage within 7 days was found in lower quintiles of SBP (OR = 0.100, 95% CI 0.011-0.887, P = 0.039 in Phase 1 quintile Q1, OR = 0.110, 95% CI 0.012-0.974, P = 0.047 in Phase 2-3 quintile Q1, and OR, 0.175, 95% CI, 0.035-0.872; P = 0.033 in Phase 4 quintile Q2, respectively). Better neurological improvement was found in SBP quintiles: Q2-Q4 (127.3-155.7 mmHg) in Phase 4 (OR = 3.095, 95% CI 1.524-6.286, P = 0.002 for Q2; OR = 2.697, 95% CI 1.354-5.370, P = 0.005 for Q3; and OR = 2.491, 95% CI 1.263-4.913, P = 0.008 for Q4, respectively). Our results also showed higher average real variability of SBP was negatively associated with better neurological outcome in Phase 1 and Phase 2-3. CONCLUSIONS: Maintaining SBP levels (≤148 mmHg) from admission to the first 24 h after thrombolysis, then keeping SBP levels (127-138 mmHg) would be beneficial.

Higher uric acid is associated with better discharge recovery and short-term outcome in stroke patients treated with thrombolysis.

BACKGROUND: Uric acid (UA) possesses antioxidant features and potential neuroprotective effects. However, conflicting results regarding the association between serum uric acid (SUA) levels and the prognosis of stroke have been obtained. We aimed to assess whether SUA is related to discharge recovery and short-term outcomes in patients who underwent thrombolysis therapy. METHODS: We recruited 393 consecutive patients who were diagnosed with acute ischaemic stroke (AIS) and treated with thrombolysis. The demographic information, including sex and age, was collected. Haematology tests, including SUA, fasting plasma glucose (FPG), and blood lipid parameters, were performed under fasting conditions the morning after admission. The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at discharge and 3 months after onset. RESULTS: A negative correlation was observed between the levels of SUA and the National Institute of Health Stroke Scale (NIHSS) score at discharge (r = - 0.171, P = 0.003). Additionally, a positive correlation was observed between the levels of SUA and the difference between the baseline NIHSS and discharge NIHSS (r = 0.118, P = 0.032). The levels of SUA in the patients with good outcomes (353.76 ± 93.05) were higher than those in the patients with poor outcomes (301.99 ± 92.24; P = 0.015) at 3 months. The multivariate logistic regression analysis demonstrated that a higher SUA level (odds ratio 0.988, 95% confidence interval 0.985-0.991, P = 0.002) was an independent predictor of a good outcome at 3 months. CONCLUSION: Higher SUA levels were associated with better discharge recovery and 3-month outcomes in patients with ischaemic stroke who received thrombolysis.