Exosome miR-23a-3p from Osteoblast Alleviates Spinal Cord Ischemia/Reperfusion Injury by Down-Regulating KLF3-Activated CCNL2 Transcription.

BACKGROUND: Spinal cord ischemia/reperfusion injury (SCIRI) is usually caused by spinal surgery or aortic aneurysm surgery and can eventually lead to paralysis or paraplegia and neurological dysfunction. Exosomes are considered as one of the most promising therapeutic strategies for SCIRI as they can pass the blood-spinal barrier. Previous studies have proved that exosomes secreted by osteocytes have a certain slowing effect on SCIRI. AIM: We aimed to explore the effect of osteoblast secreted exosomes on SCIRI. METHODS: First, neurons and osteoblasts were co-cultured under different conditions. GEO database was utilized to detect the expression of miR-23a-3p in osteoblast exosomes. SCIRI cells were treated with exosomes, and the detection was taken to prove whether miR-23a-3p could slow the progression of SCIRI. Downstream gene and the potential regulatory mechanism were explored through database and functional experiments. RESULTS: MiR-23a-3p was highly expressed in exosomes and it slowed down the process of SCIRI. Downstream mRNA KLF3 could bind to miR-23a-3p and was highly expressed in IRI. Moreover, CCNL2 was regulated by KLF3 and was highly expressed in IRI. Rescue experiments verified that miR-23a-3p suppressed the transcription of CCNL2 by targeting KLF3. CONCLUSION: Exosome miR-23a-3p from osteoblast alleviates SCIRI by down-regulating KLF3-activated CCNL2 transcription.

Effect of SGLT2 Inhibitors on Risk of Stroke in Diabetes: A Meta-Analysis.

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on reducing the risk of stroke in patients with type 2 diabetes mellitus (T2DM) remains unclear. Thus, we conducted this systemic review and meta-analysis of all relevant studies and trials to explore the role of SGLT2 inhibitors on the stroke prevention. METHODS: The present study included articles published before October 2021 and searched in Web of Science, PubMed databases. We used STATA 12.0 software to compute hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Meta-analysis indicated that SGLT2 inhibitors showed no significant effects on risk of stroke in diabetes in randomized controlled trials with a fixed effects model (HR = 0.98; 95% CI: 0.88-1.09, I2 = 22.3%, p = 0.272). Compared to other glucose-lowering drugs (oGLD) and insulin, SGLT2 inhibitors alone significantly affected risk of stroke in diabetes in observational studies with a random effects model (HR = 0.87; 95% CI: 0.80-0.95, I2 = 72.2%, p < 0.001). CONCLUSIONS: In summary, this meta-analysis indicated that the use of SGLT2 inhibitors did not decrease the risk of stroke. And for some T2DM patients with high-risk factor of stroke, SGLT2 inhibitors therapy may be more suitable compared to some oGLD such as dipeptidyl peptidase-4 inhibitors. The results of this meta-analysis are necessary to be confirmed with further studies and clinical trials.

Changes in gene expression in rat placenta at gestational day 16.5 in response to hyperglycemia.

Gestational diabetes mellitus (GDM) is a serious pregnancy complication. Hyperglycemia induces abnormal placental development and function. However, the mechanism is unclear. Previous research showed streptozocin (STZ) injection sustained hyperglycemia throughout pregnancy in rodents. Our current results showed that the placenta from hyperglycemic STZ-treated rats was about 20% heavier than that of controls. The relative thickness of each layer of the placenta was also significantly different on gestational day (GD) 16.5. Gene expression was analyzed by RNA sequencing to explore reasons for the abnormal placenta. In total, 2100 differential expressed genes (DEGs), including 1327 up-regulated and 773 down-regulated genes, were identified. Gene ontogeny (GO) analysis revealed DEGs involved in developmental process, growth, metabolic process, cell junction, molecular transducer activity and signaling. By KEGG analysis, DEGs were mainly related to the endocrine system, development, signal transduction and cell growth and death. The KEGG results were partly consistent with GO results, with DEGs mainly focused on biochemical signal pathways such as cell growth and death (e.g., Abl1, Bbc3 and Camk2d), and signal transduction (e.g., Abl1, Ceacam1 and Arnt). These genes may play a dominant role in abnormal cell proliferation and signaling disorders. These results suggest that DEGs play a role in diabetic-induced placental abnormalities. One or more of these DEGs may be involved in the etiology of placental weight increase caused by hyperglycemia.

[Randomized double-blind placebo-controlled trial of Jingfang Granules in treatment of common cold(wind-cold syndrome)].

Jingfang Granules have the effects of inducing sweating to releasing exterior, dispersing wind and dispelling dampness. Modern studies have demonstrated that it has antipyretic and antiviral activities. Therefore, this trial was conducted to evaluate the efficacy and safety of Jingfang Granules in the treatment of common cold(wind-cold syndrome). A total of 138 common cold(wind-cold syndrome) patients meeting the inclusion and exclusion criteria were randomly assigned into the experimental group(n=92) and the placebo group(n=46) at a ratio of 2∶1 and respectively received Jingfang Granules and Jingfang Granules simulation agent. The treatment lasted for 5 d, and the follow-up time was 8 d. Recovery time was employed as the main indicator of efficacy. The median reco-very time of the experimental group was 3.33 d, shorter than that 7.00 d of the placebo group. The efficacy of the experimental group was better than that of the placebo group(P<0.000 1). The major symptom severity score-time AUC of the experimental group was 489.90±206.95, which was smaller than that of the placebo group(763.50±339.53). The recovery rate and marked effective rate of the experimental group were higher than those of the placebo group, The above outcomes were statistically significant between the two groups(P<0.05). The disappearance time and rate of single symptoms including aversion to cold, nasal congestion, runny nose, cough, headache, pharyngeal itching/pain, white sputum, and somatalgia also had significant differences between the two groups(P<0.05), indicating that Jingfang Granules had good performance in alleviating the above symptoms. During the study period, one case of the experimental group had a slight increase in serum creatinine, which returned to the normal level after re-examination. The incidence of adverse reactions was 1.10%, and no serious adverse reaction was found. The two groups had no significant difference in the incidence of adverse reactions. In conclusion, Jingfang Granules can significantly shorten the course of common cold(wind-cold syndrome) and quickly alleviate the clinical symptoms, demonstrating good safety and clinical advantages.

Cell Population Data of Peripheral Leukocytes are Associated with Acute Rejection Episodes After Kidney Transplantation.

BACKGROUND: The aim of the study was to explore the association of peripheral leukocyte cell population data (CPD) with acute rejection episodes (ARE) after kidney transplantation surgery and search for potential parameters which contribute to the assessment of the occurrence of ARE. METHODS: A total of 68 patients with kidney transplants were classified into two groups according to the occurrence of ARE or not within three months after transplantation surgery (32 in ARE and 36 in non-ARE group). Hematological parameters including leukocyte CPD and serum biochemical indicators of renal function during occurrence of ARE were collected. The differences of CPD between the two groups and the association of CPD with occurrence of ARE were analyzed by SPSS software. RESULTS: Between ARE and non-ARE group, CPD parameters showed significant differences involving neutrophils, lymphocytes, and monocytes (Ne-V-sd, Ne-UMS-sd, Ly-V, Ly-MS, Ly-UMS, Ly-LS, and Mo-UMS). Ne-UMS-sd and Ly-UMS made the strongest contribution in discrimination of ARE occurrence. Ly-UMS had the largest area under the ROC (receiver operating characteristic) curve (AUC = 0.756). Meanwhile, the AUC of Ne-UMS-sd combined with Ly-UMS reached 0.823. In the ARE group, Ne-UMS-sd and Ly-UMS were inversely and linearly associated with eGFR (r = -0.527, p = 0.002; r = -0.436, p = 0.013, respectively). CONCLUSIONS: Ne-UMS-sd and Ly-UMS may be useful for the diagnosis of acute rejection episodes after kidney transplantation.

TikTok as a Health Information Source: Assessment of the Quality of Information in Diabetes-Related Videos.

BACKGROUND: Diabetes has become one of the most prevalent chronic diseases, and many people living with diabetes use social media to seek health information. Recently, an emerging social media app, TikTok, has received much interest owing to its popularity among general health consumers. We notice that there are many videos about diabetes on TikTok. However, it remains unclear whether the information in these videos is of satisfactory quality. OBJECTIVE: This study aimed to assess the quality of the information in diabetes-related videos on TikTok. METHODS: We collected a sample of 199 diabetes-related videos in Chinese. The basic information presented in the videos was coded and analyzed. First, we identified the source of each video. Next, 2 independent raters assessed each video in terms of the completeness of six types of content (the definition of the disease, symptoms, risk factors, evaluation, management, and outcomes). Then, the 2 raters independently assessed the quality of information in the videos, using the DISCERN instrument. RESULTS: In regard to the sources of the videos, we found 6 distinct types of uploaders; these included 3 kinds of individual users (ie, health professionals, general users, and science communicators) and 3 types of organizational users (ie, news agencies, nonprofit organizations, and for-profit organizations). Regarding content, our results show that the videos were primarily about diabetes management and contained limited information on the definition of the disease, symptoms, risk factors, evaluation, and outcomes. The overall quality of the videos was acceptable, on average, although the quality of the information varied, depending on the sources. The videos created by nonprofit organizations had the highest information quality, while the videos contributed by for-profit organizations had the lowest information quality. CONCLUSIONS: Although the overall quality of the information in the diabetes videos on TikTok is acceptable, TikTok might not fully meet the health information needs of patients with diabetes, and they should exercise caution when using TikTok as a source of diabetes-related information.

Short-Video Apps as a Health Information Source for Chronic Obstructive Pulmonary Disease: Information Quality Assessment of TikTok Videos.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become one of the most critical public health problems worldwide. Because many COPD patients are using video-based social media to search for health information, there is an urgent need to assess the information quality of COPD videos on social media. Recently, the short-video app TikTok has demonstrated huge potential in disseminating health information and there are currently many COPD videos available on TikTok; however, the information quality of these videos remains unknown. OBJECTIVE: The aim of this study was to investigate the information quality of COPD videos on TikTok. METHODS: In December 2020, we retrieved and screened 300 videos from TikTok and collected a sample of 199 COPD-related videos in Chinese for data extraction. We extracted the basic video information, coded the content, and identified the video sources. Two independent raters assessed the information quality of each video using the DISCERN instrument. RESULTS: COPD videos on TikTok came mainly from two types of sources: individual users (n=168) and organizational users (n=31). The individual users included health professionals, individual science communicators, and general TikTok users, whereas the organizational users consisted of for-profit organizations, nonprofit organizations, and news agencies. For the 199 videos, the mean scores of the DISCERN items ranged from 3.42 to 4.46, with a total mean score of 3.75. Publication reliability (P=.04) and overall quality (P=.02) showed significant differences across the six types of sources, whereas the quality of treatment choices showed only a marginally significant difference (P=.053) across the different sources. CONCLUSIONS: The overall information quality of COPD videos on TikTok is satisfactory, although the quality varies across different sources and according to specific quality dimensions. Patients should be selective and cautious when watching COPD videos on TikTok.

Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-l-galactose mutase.

Galactose, a monosaccharide capable of assuming two possible configurational isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Galp), or as a five-membered ring, galactofuranose (Galf). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for d-Galf Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive l-Galf production have not yet been characterized. Herein we report that efforts to decipher the sugar biosynthetic pathway and tailoring steps en route to nucleoside antibiotic A201A led to the discovery of a GDP-l-galactose mutase, MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A cluster and elucidation of 10 congeners, coupled with feeding and in vitro biochemical experiments, enabled us to: (i) decipher the unique enzyme, GDP-l-galactose mutase associated with production of two unique d-mannose-derived sugars, and (ii) assign two glycosyltransferases, four methyltransferases, and one desaturase that regiospecifically tailor the A201A scaffold and display relaxed substrate specificities. Taken together, these data provide important insight into the origin of l-Galf-containing natural product biosynthetic pathways with likely ramifications in other organisms and possible antimicrobial drug targeting strategies.

New technologies in operations and supply chains: Implications for sustainability.

In this editorial piece, we first introduce the theme and objectives of the special issue on new technologies in operations and supply chains as well as their implications for sustainability. The papers comprising the special issue are then summarized, and major findings are briefly presented. Based on our observations on the submissions and the research gaps yet to be addressed, we attempt to offer our views on the directions for future research in the same research agenda, including discussion around research scope, research theory, research methodology, and research findings as well as in-depth studies concerning contemporary and imperative issues confronting operations and supply chain managers.

Characterization of MtdV as a chorismate lyase essential to A201A biosynthesis and precursor-directed biosynthesis of new analogs.

The antimicrobial nucleoside antibiotic A201A is produced by the deep-sea derived Marinactinospora thermotolerans SCSIO 00652. Bioinformatics analysis revealed that mtdV, downstream within the A201A biosynthetic gene cluster, encodes a protein with low homology to a group of chorismate pyruvate-lyases. To explore the role of mtdV in A201A biosynthesis, mtdV was inactivated and HPLC analysis revealed that the resulting ΔmtdV mutant failed to produce A201A; production was partially restored by adding exogenous 4-hydroxybenzoic acid (4HB) to the fermentation. In vitro biochemical assays showed that MtdV catalyzes the conversion of chorismate into 4HB, thereby firmly demonstrating that MtdV is a chorismate lyase involved in A201A biosynthesis. In addition, supplementation of the ΔmtdV mutant with various 4HB analogs enabled production of seven new A201A analogs. Antimicrobial assays showed that the purified A201A analogs 3'-F-A201A and 3'-Cl-A201A were just as active as A201A against the test strains with MIC values of 1-8 µg mL-1.

Serum lipoprotein and RBC rigidity index to predict cerebral infarction in patients with carotid artery stenosis.

OBJECTIVE: This study aims to determine the risk factors and to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. METHODS: Two hundred and one subjects with carotid artery stenosis were retrospectively selected from Jinshan Branch of Shanghai Sixth People's Hospital, 115 cases of which with cerebral infarction and 86 without it. Clinical tests were performed including coagulation indices, fasting glucose, serum lipid, and blood rheology. Logistic regression analyses were used to identify the risk factors. Regression model was established, and receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value. RESULTS: Our data indicated that apolipoprotein AI (OR = 0.051, 95% CI: 0.009-0.295), lipoprotein (a) (OR = 1.003, 95% CI: 1.001-1.005), and RBC rigidity index (OR = 0.383, 95% CI: 0.209-0.702) were independent risk factors. Area under the curve (AUC) of the regression model = 0.78, with the sensitivity of 73.9% (95% CI: 64.9%-81.7%) and specificity of 69.2% (95% CI: 52.4%-83.0%). Prediction probability was determined while logistic regression score >0.748 defaulted as high-risk status. High-risk ratios were 80% in progressive cerebral infarction and 72% in nonprogressive cerebral infarction (P > .05), respectively, while significant differences were found when both compared with controls (P < .001). CONCLUSIONS: We show herein that the regression model based on apolipoprotein AI, lipoprotein (a), and RBC IR is a promising tool to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. However, identification of novel diagnostic markers for progressive cerebral infarction is still necessary.

Evaluation of the coracoclavicular reconstruction using LARS artificial ligament in acute acromioclavicular joint dislocation.

PURPOSE: The most appropriate procedure for surgical treatment of severe acromioclavicular (AC) joint dislocation was still not clear. The purpose of this study is to evaluate the outcomes of coracoclavicular (CC) reconstruction with ligament augmentation and reconstruction system (LARS) artificial ligaments for the treatment of acute complete AC joint dislocation. METHODS: Twenty-four patients (16 male and 8 female, ages ranged from 21 to 45) with acute complete AC joint dislocations were treated with CC reconstruction using LARS artificial ligaments. All these dislocations were unstable injuries. Clinical evaluation was used by the Constant scores and VAS. The radiographic evaluation consisted of Zanca radiographs for bilateral AC joint and axillary radiographs for the injured shoulder. RESULTS: All patients had follow-up times of 36 months (range 6-60). The Constant scores rose from 62.3 ± 6.9 preoperatively to 94.5 ± 9.3 at final evaluation (P < 0.05). Preoperative VAS scores were 5.1 ± 1.7, and the VAS scores at the last review were 0.7 ± 1.4 (P < 0.05). Follow-up radiographs showed anatomical reduction in 20 patients and slight loss of reduction in 4 patients. Calcification of CC ligament in 4 patients, degenerative change around the AC joint in 2 patient and clavicular osteolysis around screws in one patient were found. CONCLUSIONS: LARS artificial ligament for reconstruction of CC can provide immediate stability and allow early shoulder mobilization with good functional results and few complications. This procedure was an effective and safe method to treat grade III and more AC joint dislocations. LEVEL OF EVIDENCE: IV.

Exploring the relationship between older adults' online health information seeking, negative emotions and prevention behaviors in the pandemic context: a two-wave longitudinal study.

Introduction: During the COVID-19 pandemic, older adults were facing more mental health issues that may cause complex impacts on pandemic prevention, and turning to the internet for health information is a double-edged sword for them. This study aimed to investigate the reciprocal relationship between negative emotions and prevention behaviors in older adults, as well as the direct and moderating effects of online health information seeking (OHIS) on negative emotions and prevention behaviors. Methods: Based on the common-sense model of self-regulation (CSM) and a sample of more than 20,000 participants from the Survey of Health, Aging and Retirement in Europe (SHARE), this study first used an autoregressive cross-lagged panel model (CLPM) to analyze the longitudinal effect of negative emotions on prevention behaviors. Second, the study used ordinary least squares (OLS) regression to explore the influence of OHIS usage frequency changes on negative emotions and prevention behaviors. Third, the study used multigroup analysis to examine the moderating effect of OHIS usage frequency changes on the CLPM. Results: The findings indicate a significant longitudinal association where initial negative emotions predicted later prevention behaviors (ß = 0.038, p < 0.001), and increased OHIS frequency was linked to positive changes in prevention behavior (ß = 0.109, p < 0.001). Multigroup analysis revealed that the connection between negative emotions or increased negative emotions and prevention behaviors remained significant for those with no change or an increase in OHIS frequency but not for those with a decrease. Conclusion: This study suggested that negative emotions may drive older adults to engage more in prevention behaviors and that OHIS can augment this effect. These results underscore the importance of addressing mental health and providing reliable online health information to support older adults in managing infectious disease risks.

TIE2 expression in hypertensive ICH and its therapeutic modulation with AKB-9778: Implications for brain vascular health.

Hypertensive intracerebral hemorrhage (ICH) is a devastating condition, the molecular underpinnings of which remain not fully understood. By leveraging high-throughput transcriptome sequencing and network pharmacology analysis, this study unveils the significant role of the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) in ICH pathogenesis. Compared to controls, a conspicuous downregulation of TIE2 was observed in the cerebral blood vessels of hypertensive ICH mice. In vitro assays with human brain microvascular endothelial cells (HBMEC), HBEC-5i revealed that modulation of TIE2 expression significantly influences cellular proliferation, migration, and angiogenesis, mediated via the Rap1/MEK/ERK signaling pathway. Notably, the small molecule AKB-9778 was identified to target and activate TIE2, affecting the functional attributes of HBEC-5i. In vivo experiments further demonstrated that combining AKB-9778 with antihypertensive drugs could mitigate the incidence and volume of bleeding in hypertensive ICH mouse models, suggesting potential therapeutic implications.

A spinal circuit model with asymmetric cervical-lumbar layout controls backward locomotion and scratching in quadrupeds.

Locomotion and scratching are basic motor functions which are critically important for animal survival. Although the spinal circuits governing forward locomotion have been extensively investigated, the organization of spinal circuits and neural mechanisms regulating backward locomotion and scratching remain unclear. Here, we extend a model by Danner et al. to propose a spinal circuit model with asymmetrical cervical-lumbar layout to investigate these issues. In the model, the left-right alternation within the cervical and lumbar circuits is mediated by V 0D and V 0V commissural interneurons (CINs), respectively. With different control strategies, the model closely reproduces multiple experimental data of quadrupeds in different motor behaviors. Specifically, under the supraspinal drive, walk and trot are expressed in control condition, half-bound is expressed after deletion of V 0V CINs, and bound is expressed after deletion of V0 (V 0D and V 0V) CINs; in addition, unilateral hindlimb scratching occurs in control condition and synchronous bilateral hindlimb scratching appears after deletion of V 0V CINs. Under the combined drive of afferent feedback and perineal stimulation, different coordination patterns between hindlimbs during BBS (backward-biped-spinal) locomotion are generated. The results suggest that (1) the cervical and lumbar circuits in the spinal network are asymmetrically recruited during particular rhythmic limb movements. (2) Multiple motor behaviors share a single spinal network under the reconfiguration of the spinal network by supraspinal inputs or somatosensory feedback. Our model provides new insights into the organization of motor circuits and neural control of rhythmic limb movements.

Safety and effectiveness of weighted blankets for symptom management in patients with mental disorders: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current practice guideline regarding treatment for insomnia and sleep disturbances among children and adolescents with autism spectrum disorder (ASD) has been published and it suggests that the use of weighted blankets might not be an evidence-informed practice. However, limited guidance and evidence synthesis exist on the overall effectiveness of a weighted blanket for symptom management among patients with mental disorders, although it has been routinely recommended and prescribed for this population in many mental health care settings. OBJECTIVE: To systematically evaluate and synthesize existing data on the safety and effectiveness of weighted blankets for symptom management among patients with mental disorders. METHODS: Comprehensive retrieval of published, unpublished, or ongoing studies was carried out across a series of bibliographic databases, grey literature sources, and clinical trial registry platforms, along with manual screening of the reference lists of the included studies or relevant reviews. Randomized controlled trials (RCTs) were included if they compared a weighted blanket intervention and a control condition among patients with mental disorders. Two reviewers independently extracted the data using a pre-specified form and assessed the methodological quality of the included studies with the revised Cochrane 'Risk of Bias' (RoB 2) tool. Review Manager (RevMan) 5.3 software was used to conduct the meta-analysis when possible. Subgroup and sensitivity analyses, where appropriate, were conducted to explore the robustness of the pooled effect estimates. RESULTS: Eight studies involving a total of 426 patients were included in this review. Half of the included studies were rated as having a high risk of bias, primarily due to the failure to blind participants for participant-reported measures. No serious adverse events were reported with the application of weighted blankets. The meta-analysis of five studies revealed that the use of weighted blankets induced a small magnitude decrease (standardized mean difference within studies [SMD]= 0.40) in anxiety management. The pooled estimate of three studies reporting the effect of weighted blankets on insomnia revealed a nonsignificant difference between the two groups (mean difference [MD] = -1.92, 95 % confidence interval [CI] = -3.92-0.09, p = 0.06). However, the leave-one-out sensitivity analysis of the two remaining homogeneous studies revealed that patients who used weighted blankets had reduced insomnia severity index (ISI) scores (MD = -2.78, 95 % CI = -4.44 to -1.12, p = 0.001). Additionally, a study without available data for inclusion in the meta-analysis also reported a positive effect in reducing the ISI score. Due to the heterogeneity across studies, summary estimates for the effects of weighted blankets on fatigue and depression were not computed. However, primary studies reporting these two outcomes demonstrated that the application of weighted blankets had a positive effect. CONCLUSION: Weighted blankets may be a safe and effective add-on treatment for managing common symptoms such as anxiety, insomnia, depression, and fatigue among psychiatric patients. However, these results need to be further confirmed due to the limited number of studies included in this review, the small sample size and the significant heterogeneity across these primary studies. To gain a better understanding of the effect and mechanism of weight blankets, future trials should preferably integrate more objective measures.

Mitigating the influence of message features on health misinformation sharing intention in social media: Experimental evidence for accuracy-nudge intervention.

RATIONALE: The escalating dissemination of health misinformation on social media platforms poses a significant threat to users' well-being. It is imperative to identify the types of health misinformation that are more susceptible to widespread dissemination and to explore strategies to curb its spread. METHOD: This study designed a 2 (emotional appeal type: positive vs. negative) × 2 (fabricated source type: pseudo-common vs. pseudo-authoritative) × 2 (accuracy-nudge label: No vs. Yes) online between-subjects experiment controlling for factors such as e-health literacy, prior sharing experience, and personal involvement. A snowball sampling approach was used to recruit 1952 participants through social media, resulting in a final sample of 1393 valid responses. RESULTS: Compared to positive emotional appeal and pseudo-common sources, negative emotional appeal and pseudo-authoritative sources resulted in higher levels of sharing intention. Under the condition of negative emotional appeal, the promotion effect of pseudo-authoritative sources on sharing intention was intensified. The accuracy-nudge intervention could significantly mitigate this tendency. The underlying mechanisms revealed more details: both negative emotional appeals and pseudo-authoritative sources increased the perceived credibility of health misinformation, thereby increasing users' sharing intention. However, in contrast to pseudo-authoritative sources, excessive negative emotional appeal induced vigilant verification behavior among users, which reduced sharing to some extent. Adding an accuracy-nudge label to health misinformation reduced users' misguided trust in health misinformation features and stimulated information verification, ultimately reducing health misinformation sharing intention. CONCLUSIONS: Negative emotional appeal and pseudo-authoritative sources can enhance the perceived credibility of health misinformation, thereby strengthening the sharing intention of social media users. Therefore, health misinformation with negative emotional appeal and pseudo-authoritative sources is more likely to be widely shared. The accuracy nudge intervention can trigger users' information verification behavior, suppress the persuasive effects of the misinformation features mentioned above, and help prevent the spread of health misinformation on social media.

Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.

BACKGROUND: Ginsenoside Rg3 is a component of ginseng that protects against myocardial ischemia/reperfusion (MI/R) injury. Ferroptosis is a new form of cell death characterized by oxidative damage to phospholipids. The purpose of this study was to examine the role and of ginsenoside Rg3 in MI/R and the mechanism. METHODS: A mouse model of left anterior descending (LAD) ligation-induced myocardial ischemia/reperfusion (MI/R) injury and oxygen-glucose deprivation/reperfusion (OGD/R) were used as in vitro and in vivo models, respectively. Echocardiographic analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (H&E) staining were used to assess the cardioprotective effects of ginsenoside Rg3. Western blotting, biochemical analysis, small interfering RNA analysis and molecular docking were performed to examine the underlying mechanism. RESULTS: Ginsenoside Rg3 improved cardiac function and infarct size in mice with MI/R injury. Moreover, ginsenoside Rg3 increased the expression of the ferroptosis-related protein GPX4 and inhibited iron deposition in mice with MI/R injury. Ginsenoside Rg3 also activated the Nrf2 signaling pathway. Ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the Nrf2 signaling pathway. Notably, ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to attenuate OGD/R-induced ferroptosis in H9C2 cells. Taken together, ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway. CONCLUSIONS: Our findings demonstrated that ginsenoside Rg3 ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.

Institutional pressures, dynamic capabilities and environmental management systems: investigating the ISO 9000--environmental management system implementation linkage.

We hypothesize a model where domestic and international institutional pressures lead to the successful implementation of ISO 9000 and can in turn lead to the successful implementation of environmental management systems such as ISO 14001 environmental certification systems or total quality environmental management (TQEM) systems. Using appropriate tests for mediation with dichotomous mediators and outcomes, we find that the model holds for a sample of 377 Chinese manufacturers in six major industrial groups in Suzhou, Dalian, and Tianjin. Our findings are consistent with the theory linking internal capabilities to heterogeneous external (in this case, institutional) pressures on organizations for environmentally proactive efforts. Our findings suggest that institutions in developing countries with significant environmental concerns such as China as well as foreign suppliers and partners to firms in these countries should encourage and support ISO 9000 implementations by local firms. These findings may influence other developing nations' adoption of quality and environmental process systems.