Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in ...patients with hypercholesterolemia.
In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule).
A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase.
Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo.
ClinicalTrials.gov , number NCT03944109.
Driven by sustainable development, the energy-saving manufacturing and on-site repairing processes for fiber-reinforced polymer (FRP) composites are highly desired to replace the conventional ...autoclave or oven. In this work, the flexible, thin free-standing laser-induced graphene (FS-LIG) film was obtained by one-step laser irradiation on polybenzoxazine resin followed by rapid quench-peeling. The FS-LIG film showed the uniform, low-voltage driven, and long-term stable Joule heating effect. With attractive Joule performance, the FS-LIG film was developed as a heater for the out-of-autoclave fabrication of FRP composites. Compared with the conventional oven curing process, the FS-LIG-based Joule heating saved around 45% of the energy required without compromising the mechanical performance of obtained composites. Moreover, the FS-LIG film was interlayered into FRP composites to prepare the self-heating patch, which could not only provide heat for the on-site repair of structural composites but also serve as the reinforcement for mechanical properties. Furthermore, the integration of FS-LIG layer enabled the cured composites with additional functionalities including temperature and mechanical sensing to monitor the structural health of composites. This easy-fabricated FS-LIG heater showed enormous practical promise in the advanced manufacturing and repairing of composites.
Graphical abstract
Worldwide, overweight and obesity have become an important public health problem affecting the health of children and adolescents. In China, the prevalence of overweight and obesity has reached 19 ...percent among the 6-17-year-old age group. Although studies have shown that regular consumption of sugar-sweetened beverages (SSBs), especially sugar-sweetened carbonated beverages (SSCBs), is positively correlated with overweight and obesity among children, the research on ways to reduce SSBs consumption is scarce. This study fills this gap by analyzing data on nearly 4000 students aged between 9-15 from the Inner Mongolia Autonomous Region in China, exploring possible influential pathways between subjective dietary knowledge, SSCBs consumption, and child obesity. The estimation results show that SSCBs consumption significantly mediates the relationship between dietary knowledge and the incidence of overweight and obesity; the mediated effects are different among subgroups. Therefore, improving dietary knowledge related to the lowing of SSBs consumption to reduce the obesity risk may be considered a possible way to reduce the prevalence of overweight and obesity among children.
Angiotensin II (ANG II) is associated with fibrosis in both clinical and basic studies. Thus, we aimed to explore a mechanism by which ANG II induces fibrosis. 5 μM of ANG II was used in the in vitro ...study. The mouse cardiovascular fibrosis model was established by infused with AngII (1000 ng/kg/min) for 7 days and cotreated with lovastatin (10 mg/kg daily) or vehicle control (DMSO in saline). We found that ANG II activated yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), two transcription factors that were shown to induce fibrosis. Inhibition of ras homolog gene family member A (RhoA) reduced ANG II-induced YAP/TAZ transcriptional activity, which suggests that the upregulation of YAP/TAZ signaling by ANG II is RhoA-dependent. Furthermore, studies have shown that the inhibition of YAP/TAZ by either siRNA or small molecule inhibitor suppressed ANG II-induced expression of fibrogenic genes, indicating that ANG II upregulates YAP/TAZ to initiate fibrosis. The mevalonate pathway, which is targeted by statins, has also been shown to control YAP/TAZ. Here, we found that the suppression of YAP/TAZ signaling by lovastatin attenuates ANG II-induced fibrosis, both in vitro and in vivo. These data reveal a novel mechanism for ANG II in the induction of fibrosis. In addition, our findings provide a reasonable explanation regarding the mechanism by which statins improve fibrosis in patients with cardiovascular and renal diseases.
•ANG II activates YAP/TAZ signaling via RhoA-dependent pathway.•ANG II induces fibrosis in a YAP/TAZ dependent manner.•Lovastatin attenuates fibrosis might through downregulate YAP/TAZ.
Quantitative photoacoustic tomography (qPAT) holds great potential in estimating chromophore concentrations, whereas the involved optical inverse problem, aiming to recover absorption coefficient ...distributions from photoacoustic images, remains challenging. To address this problem, we propose an extractor-attention-predictor network architecture (EAPNet), which employs a contracting–expanding structure to capture contextual information alongside a multilayer perceptron to enhance nonlinear modeling capability. A spatial attention module is introduced to facilitate the utilization of important information. We also use a balanced loss function to prevent network parameter updates from being biased towards specific regions. Our method obtains satisfactory quantitative metrics in simulated and real-world validations. Moreover, it demonstrates superior robustness to target properties and yields reliable results for targets with small size, deep location, or relatively low absorption intensity, indicating its broader applicability. The EAPNet, compared to the conventional UNet, exhibits improved efficiency, which significantly enhances performance while maintaining similar network size and computational complexity.
Migraine-a disabling neurological disorder, imposes a tremendous burden on societies. To reduce the economic and health toll of the disease, insight into its pathophysiological mechanism is key to ...improving treatment and prevention. Resting-state functional magnetic resonance imaging (rs-fMRI) studies suggest abnormal functional connectivity (FC) within the default mode network (DMN) in migraine patients. This implies that DMN connectivity change may represent a biomarker for migraine. However, the FC abnormalities appear inconsistent which hinders our understanding of the potential neuropathology. Therefore, we performed a meta-analysis of the FC within the DMN in migraine patients in the resting state to identify the common FC abnormalities. With efficient search and selection strategies, nine studies (published before July, 2022) were retrieved, containing 204 migraine patients and 199 healthy subjects. We meta-analyzed the data using the Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) method. Compared with healthy subjects, migraine patients showed increased connectivity in the right calcarine gyrus, left inferior occipital gyrus, left postcentral gyrus, right cerebellum, right parahippocampal gyrus, and right posterior cingulate gyrus, while decreased connectivity in the right postcentral gyrus, left superior frontal gyrus, right superior occipital gyrus, right orbital inferior frontal gyrus, left middle occipital gyrus, left middle frontal gyrus and left inferior frontal gyrus. These results provide a new perspective for the study of the pathophysiology of migraine and facilitate a more targeted treatment of migraine in the future.
Background
Irritable bowel syndrome (IBS) is a brain-gut disorder with high global prevalence, resulting from abnormalities in brain connectivity of the default mode network and aberrant changes in ...gray matter (GM). However, the findings of previous studies about IBS were divergent. Therefore, we conducted a meta-analysis to identify common functional and structural alterations in IBS patients.
Methods
Altogether, we identified 12 studies involving 194 IBS patients and 230 healthy controls (HCs) from six databases using whole-brain resting state functional connectivity (rs-FC) and voxel-based morphometry. Anisotropic effect-size signed differential mapping (AES-SDM) was used to identify abnormal functional and structural changes as well as the overlap brain regions between dysconnectivity and GM alterations.
Results
Findings indicated that, compared with HCs, IBS patients showed abnormal rs-FC in left inferior parietal gyrus, left lingual gyrus, right angular gyrus, right precuneus, right amygdala, right median cingulate cortex, and left hippocampus. Altered GM was detected in the fusiform gyrus, left triangular inferior frontal gyrus (IFG), right superior marginal gyrus, left anterior cingulate gyrus, left rectus, left orbital IFG, right triangular IFG, right putamen, left superior parietal gyrus and right precuneus. Besides, multimodal meta-analysis identified left middle frontal gyrus, left orbital IFG, and right putamen as the overlapped regions.
Conclusion
Our results confirm that IBS patients have abnormal alterations in rs-FC and GM, and reveal brain regions with both functional and structural alterations. These results may contribute to understanding the underlying pathophysiology of IBS.
Systematic review registration
https://www.crd.york.ac.uk/prospero
, identifier CRD42022351342.
The use of in-hole imaging to investigate geological structure characteristics is one of the crucial methods for the study of rock mass stability and rock engineering design. The in-hole images are ...usually influenced by the lighting and imaging characteristics, resulting in the presence of interference noise regions in the images and consequently impacting the classification accuracy. To enhance the analytical efficacy of in-hole images, this paper employs the proposed optimal non-concentric ring segmentation method to establish a new database. This method establishes the transformation function based on the Ansel Adams Zone System and the fluctuation values of the grayscale mean, adjusting the gray-level distribution of images to extract two visual blind spots of different scales. Thus, the inner and outer circles are located with these blind spots to achieve the adaptive acquisition of the optimal ring. Finally, we use the optimal non-concentric ring segmentation method to traverse all original images to obtain the borehole image classification database. To validate the effectiveness of this method, we conduct experiments using various segmentation and classification evaluation metrics. The results show that the Jaccard and Dice of the optimal non-concentric ring segmentation approach are 88.43% and 98.55%, respectively, indicating superior segmentation performance compared to other methods. Furthermore, after employing four commonly used classification models to validate the performance of the new classification database, the results demonstrate a significant improvement in accuracy and macro-average compared to the original database, with the highest increase in accuracy reaching 4.2%. These results fully demonstrate the effectiveness of the proposed optimal non-concentric ring segmentation method.
Anxiety disorder is a common psychiatric illness. Medicinal herbs have become a field of interest in the treatment of anxiety. This study aimed to evaluate and compare the efficacy and acceptability ...of all possible medicinal herbs for the treatment of anxiety.
A Bayesian network meta-analysis was conducted for adults with diagnosed or subthreshold anxiety in randomized controlled trials identified in PubMed, EMBASE, the Cochrane Library, and Web of Science, searched between Jan 1, 1987, and Dec 31, 2021. The outcomes included efficacy (measured by endpoint Hamilton Anxiety Scale HAMA Scores) and acceptability (discontinuation by ineffectiveness, worsening of the symptoms, or adverse events).
A total of 29 trials were reviewed, comparing 12 medicinal herbs. Silexan (mean difference MD: −3.84, 95% credible interval CrI: −6.31 to −1.34) displayed a significant effect on anxiety, and possibly benefitted the treatment of depression (standard mean difference SMD: −0.37, 95% confidence interval CI: −0.53 to −0.20) and insomnia (SMD: −0.48, 95% CI: −0.76 to −0.21). Kava was found to be an effective anxiolytic (MD: −2.46, 95% CrI: −4.47 to −0.32) but possibly ineffective in patients with generalized anxiety disorder (MD: −0.17, 95% CrI: −2.55 to −1.97). Ginkgo biloba (MD: −4.63, 95% CrI: −9.01 to −0.23) and Withania somnifera (MD: −4.90, 95% CrI: −9.70 to −0.17) were efficacious, as measured by HAMA scores but the trials were limited by their small sample sizes. Galphimia glauca (MD: −1.23, 95% CrI: −4.68 to 2.23) and Manasamitravn Vataka (MD: −1.35, 95% CrI: −7.39 to 4.68) exhibited the same anxiolytic effect as standard treatments, but both were absent from trials that were rated low risk, highlighting that confidence in their ability to provide an anxiolytic effect requires additional study. Conversely, although Passionflower (MD: −4.20, 95% CrI: −8.82 to 0.16) and Saffron (MD: −2.71, 95% CrI: −6.06 to 0.57) did not reduce HAMA scores significantly in the summary network, both were worthy of further study because of support from separate networks. There was insufficient evidence to confirm the effectiveness of Valerian (MD: 0.95, 95% CrI: −6.57 to 8.42) in standard-controlled estimation or the ineffectiveness of Chamomile (MD: 0.54, 95% CrI: −5.13 to 6.25) compared with a placebo for anxiety. Gamisoyo-san (MD: −0.98, 95% CrI: −6.48 to 4.54) and L-theanine (MD: −0.49, 95% CrI: −6.54 to 5.57) did not outperform a placebo for the treatment of anxiety in terms of statistical certainty. All medicinal herbs were well-tolerated and exhibited a good safety profile compared with control groups. When all herbs were compared, there was no statistical evidence to suggest any comparison significantly reduced HAMA scores except Ginkgo biloba vs Kava (MD: −4.41, 95% CrI: −8.32 to −0.35), although Ginkgo biloba was ranked as worst due to its poor tolerability.
Medicinal herbs may be promising for the treatment of anxiety. However, these results should be considered preliminary because of the unconvincing sample sizes, together with the potential effectiveness of placebos.
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