Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial.

BACKGROUND: Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. METHODS: This phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial was conducted in 75 centres in 20 countries. We enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or juvenile psoriatic arthritis, and an inadequate response (after ≥12 weeks of treatment) or intolerance to one or more conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period (10 weeks for the safety and pharmacokinetic subcohort), and an up to 32-week placebo-controlled double-blind withdrawal period. After age-based dosing was established in the safety and pharmacokinetic period, patients received a once-daily 4 mg adult-equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib, and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Patients and any personnel interacting directly with patients or sites were masked to group assignment. The primary endpoint was time to disease flare during the double-blind withdrawal period and was assessed in the intention-to-treat population of all randomly assigned patients. Safety was assessed in all patients who received at least one dose of baricitinib throughout the three trial periods. For adverse events in the double-blind withdrawal period, exposure-adjusted incidence rates were calculated. The trial was registered on ClinicalTrials.gov, NCT03773978, and is completed. FINDINGS: Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled and received at least one dose of baricitinib (152 [69%] girls and 68 [31%] boys; median age 14·0 years [IQR 12·0-16·0]). 219 patients received baricitinib in the open-label lead-in period, of whom 163 (74%) had at least a JIA-ACR30 response at week 12 and were randomly assigned to placebo (n=81) or baricitinib (n=82) in the double-blind withdrawal period. Time to disease flare was significantly shorter with placebo versus baricitinib (hazard ratio 0·241 [95% CI 0·128-0·453], p<0·0001). Median time to flare was 27·14 weeks (95% CI 15·29-not estimable) in the placebo group, and not evaluable for patients in the baricitinib group (<50% had a flare event). Six (3%) of 220 patients had serious adverse events during the safety and pharmacokinetic period or open-label lead-in period. In the double-blind withdrawal period, serious adverse events were reported in four (5%) of 82 patients (incidence rate [IR] 9·7 [95% CI 2·7-24·9] per 100 patient-years at risk) in the baricitinib group and three (4%) of 81 (IR 10·2 [2·1-29·7]) in the placebo group. Treatment-emergent infections were reported during the safety and pharmacokinetic or open-label lead-in period in 55 (25%) of 220 patients, and during the double-blind withdrawal period in 31 (38%) of 82 (IR 102·1 [95% CI 69·3-144·9]) in the baricitinib group and 15 (19%) of 81 (IR 59·0 [33·0-97·3]) in the placebo group. Pulmonary embolism was reported as a serious adverse event in one patient (1%; IR 2·4 [95% CI 0·1-13·3]) in the baricitinib group in the double-blind withdrawal period, which was judged to be related to study treatment. INTERPRETATION: Baricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy. FUNDING: Eli Lilly and Company under licence from Incyte.

Diagnostic and prognostic significance of miR-320a-3p in patients with chronic heart failure.

AIM: The purpose of this study was to investigate the diagnostic and prognostic value of miR-320a-3p in chronic heart failure (CHF). METHODS: A total of 103 patients with CHF and 95 healthy controls were included in the study population. The expression level of serum miR-320a-3p was detected by qRT-PCR. The diagnostic effect of miR-320a-3p on CHF was evaluated by receiver operating characteristic curve. Kaplan-Meier curve and Cox regression were used to analyze the risk factors for 4-year prognosis of CHF patients. Bioinformatics analysis was used to analyze the possible target genes of miR-320a-3p and related signaling pathways. RESULTS: Serum miR-320a-3p expression was increased in CHF patients, and the levels of BNP and LVEF were positively and negatively correlated with miR-320a-3p, respectively. The AUC value of ROC curve was 0.866, indicating that miR-320a-3p had high diagnostic accuracy for CHF. Survival curve and Cox analysis showed that high expression of miR-320a-3p was associated with poor prognosis in CHF patients, and age and miR-320a-3p were independent risk factors for prognosis in CHF patients. GO and KEGG analysis showed that the downstream target genes of miR-320a-3p were involved in biological processes such as cell adhesion, stem cell differentiation and neural development, and were enriched in mTOR, TNF, AMPK and other signaling pathways. CONCLUSIONS: miR-320a-3p increased abnormally in CHF and was related to the severity of CHF. miR-320a-3p has the potential to be a diagnostic and prognostic marker for CHF.

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.

Clinical Significance and Potential Mechanism of Circ_00008842 in Acute Myocardial Infarction.

This study aimed to evaluate the clinical value of circ_0008842 in acute myocardial infarction (AMI) and explore the potential mechanisms.GSE149051 and GSE160717 datasets analyze common differentially expressed circRNAs (coDEcircRNA) in AMI. RT-qPCR analysis of circ_0008842 mRNA levels in patients with AMI. ROC curve assesses the diagnostic value of circ_0008842 in AMI. A cell model of AMI was constructed by hypoxia-reoxygenation (H/R) -induced H9c2. Cell viability and apoptosis were examined by CCK-8 and flow cytometry. Enzyme-linked immunosorbent assay was used to explore myocardial injury markers CK-MB and cTnI secretion. Dual luciferase reporter assays validate circ_0008842 binding to miRNA. PPI network and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment reveal potential functions and pathways of targets from the miRNA in AMI.circ_0008842 is recognized as coDEcircRNA in AMI-related databases. circ_0008842 was greatly lower and miR-574-5p was significantly higher in patients with AMI than in healthy individuals. miR-574-5p is a target of circ_0008842. The sensitivity and specificity of circ_0008842 for diagnosing patients with AMI were 87.40% and 83.50%, respectively. Overexpression of circ_0008842 inhibited H/R induced apoptosis, increased cell viability, and decreased CK-MB and cTnI levels, which were partially abrogated by overexpression of miR-574-5p. Calmodulin-like protein 4 (CALML4) was the most connected hub gene in the PPI network of miR-574-5p predicted target genes.circ_0008842 is a diagnostic biomarker for AMI and participates in myocardial injury in AMI by regulating miR-574-5p. Our study provides new insights into the diagnosis for AMI.

Estimands, Handling of Missing Data and Impact on Assumed Effect Size and Power in Pivotal COVID-19 Treatment Trials.

Estimands play an important role for aligning study objectives, study design and analyses through a precise definition of the quantity of interest. For COVID-19 studies, apart from intercurrent events, high volume of missing data has been observed. We explore their impact on several estimands through a synthetic COVID-19 data generated from a discrete-time multi-state model. We compare estimators of these estimands based on their ability to closely match the true response rates and retain assumed power. The final choice of the estimand then needs to be aligned with clinically meaningful quantities of interest to patients, clinicians, regulators and payers.

Profile probing of suspended particles in water by Stokes vector polarimetry.

Suspended particles are the important components of natural water. In this paper, a method based on polarized light scattering is proposed for profile probing of the particulate components in water. The profile probing is achieved by a polarized light sheet illuminating the suspension and the Stokes vector imaging system at a 120° backscattering angle, receiving the scattered light of the particles in the scattering volume. Each Stokes vector image (SVI) includes hundreds of star-studded particles whose Stokes vectors are used to retrieve the numbers of each particulate component in water. Experiments of typical particles are conducted. The classifications of these particles powered by the convolutional neural network (CNN) are demonstrated. The particulate components in mixed samples are successfully recognized and quantitatively compared. Considering at least 10 SVIs every second, the concentrations of each particulate component in water are effectively evaluated. The concept of profile probing the particulate components in water is proved to be powerful, by which we can measure up to almost 8000 particles per second. These results encourage the development of in-situ tools with this concept for particle profiling in future field surveying.

Deep learning Mueller matrix feature retrieval from a snapshot Stokes image.

A Mueller matrix (MM) provides a comprehensive representation of the polarization properties of a complex medium and encodes very rich information on the macro- and microstructural features. Histopathological features can be characterized by polarization parameters derived from MM. However, a MM must be derived from at least four Stokes vectors corresponding to four different incident polarization states, which makes the qualities of MM very sensitive to small changes in the imaging system or the sample during the exposures, such as fluctuations in illumination light and co-registration of polarization component images. In this work, we use a deep learning approach to retrieve MM-based specific polarimetry basis parameters (PBPs) from a snapshot Stokes vector. This data post-processing method is capable of eliminating errors introduced by multi-exposure, as well as reducing the imaging time and hardware complexity. It shows the potential for accurate MM imaging on dynamic samples or in unstable environments. The translation model is designed based on generative adversarial network with customized loss functions. The effectiveness of the approach was demonstrated on liver and breast tissue slices and blood smears. Finally, we evaluated the performance by quantitative similarity assessment methods in both pixel and image levels.

Mueller matrix imaging with a spatially modulated polarization light source.

In this paper, we present a Mueller matrix imaging system consisting of a spatially modulated polarization light source (SMPL) and a dual division-of-focal-plane (DoFP) polarimeters as the PSA and 2D detector. The system does not contain moving parts such as a rotating stage, which leads to more robust and reliable operations for applications in hostile settings. By taking Muller matrix images at variable distances between the SMPL and the target, we examine in details errors due to different spatial distributions in angle and intensity of different polarized lights. A calibration method is proposed to reduce such errors introduced by SMPL. The performances of the new imaging technique and the calibration method are tested in Mueller matrix imaging of different samples.

Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4).

BACKGROUND: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate-to-severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). METHODS: In this double-blind, randomized, placebo-controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night-time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment-emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. CONCLUSIONS: Baricitinib 4 mg + TCS improved the signs and symptoms of moderate-to-severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate-to-severe AD. What is already known about this topic? Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients. Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add? Baricitinib combined with background low- or moderate-potency topical corticosteroids provided improvements in the signs and symptoms of moderate-to-severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A. The most common treatment-emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache. The safety profile was consistent with previous studies in patients with moderate-to-severe atopic dermatitis.

Dynamic incorporation of real world evidence within the framework of adaptive design.

For the clinical studies in rare diseases or small patient populations, having an adequately powered randomized controlled trial is further complicated by variability. As such, sample size re-estimation can be a useful tool if at an interim look the trial sample size needs to be increased to achieve adequate power to reject the null hypothesis. Meanwhile, borrowing or extrapolating information from real-world data or real-world evidence has gained increasing use in trial design and analysis since 2014. Combining these two strategies, high-quality real-world data, if leveraged properly, has the potential to generate real-world evidence that can assist interim decision-making, lower enrollment burden, and reduce study timeline and costs. With proper borrowing from historical control, some of the challenges in these high unmet medical need studies could be resolved considerably. We examine the incorporation of real-world evidence within the framework of adaptive design strategy in pediatric type II diabetes trials where recruitment has been challenging and the completion is hardly on time. Simulations under various scenarios are conducted to assess the borrowing strategy, i.e., the matching method in combination of sample size re-estimation. Comparisons of performance metrics are presented to showcase the advantages of proposed method.

Uncovering the disposable face masks as vectors of metal ions (Pb(â ¡), Cd(â ¡), Sr(â ¡)) during the COVID-19 pandemic.

The demand for disposable face masks (DFMs) increased sharply in response to the COVID-19 pandemic. However, information regarding the underlying roles of the largely discarded DFMs in the environment is extremely lacking. This study focused on the pristine and UV-aged DFMs as vectors of metal ions (Pb(Ⅱ), Cd(Ⅱ), and Sr(Ⅱ)). Further, the aging mechanism of DFMs with UV radiation as well as the interaction mechanisms between DFMs and metal ions were investigated. Results revealed that the aging process would help to promote more metal ions adsorbed onto DFMs, which was mainly attributed to the presence of oxygen-containing groups on the aged DFMs. The adsorption affinity of pristine and aged DFMs for the metal ions followed Pb(Ⅱ) > Cd(Ⅱ) > Sr(Ⅱ), which was positively corrected with the electronegativity of the metals. Interestingly, we found that even if DFMs were not disrupted, DFMs had similar or even higher adsorption affinity for metals compared with other existing microplastics. Besides, regarding environmental factors, including salinity and solution pH played a crucial role in the adsorption processes, with greater adsorption capacities for pristine and aged DFMs at higher pH values and low salinity. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and density functional theory further confirmed that the pristine DFMs interacted with the metals mainly through electrostatic interaction, while electrostatic interaction and surface complexation jointly regulated the adsorption of the metals onto aged DFMs. Overall, these findings would help to evaluate environmental behaviors and risks of DFMs associated with metals.

Win ratio approach for analyzing composite time-to-event endpoint with opposite treatment effects in its components.

There is an increasing interest in the use of win ratio with composite time-to-event due to its flexibility in combining component endpoints. Exploring this flexibility further, one interesting question is in assessing the impact when there is a difference in treatment effect in the component endpoints. For example, the active treatment may prolong the time to occurrence of the negative event such as death or ventilation; meanwhile, the treatment effect may also shorten the time to achieving positive events, such as recovery or improvement. Notably, this portrays a situation where the treatment effect on time to recovery is in a different direction of benefit compared to the time to ventilation or death. Under such circumstances, if a single endpoint is used, the benefit gained for other individual outcomes is not counted and is diminished. As consequence, the study may need a larger sample size to detect a significant effect of treatment. Such a scenario can be handled by win ratio in a novel way by ranking component events, which is different from the usual composite endpoint approach such as time-to-first event. To evaluate how the different directions of treatment effect on component endpoints will impact the win ratio analysis, we use a Clayton copula-based bivariate survival simulation to investigate the correlation of component time-to-event. Through simulation, we found that compared to the marginal model using single endpoints, the win ratio analysis on composite endpoint performs better, especially when the correlation between two events is weak. Then, we applied the methodology to an infectious disease progression simulated study motivated by COVID-19. The application demonstrates that the win ratio approach offers advantages in empirical power compared to the traditional Cox proportional hazard approach when there is a difference in treatment effect in the marginal events.

Stress Detection of Conical Frustum Windows in Submersibles Based on Polarization Imaging.

Stress detection of the conical frustum window is a very important issue to ensure the safety of deep manned submersibles. In this paper, we propose a method based on polarization imaging to evaluate the stress accumulation and recovery in the conical frustum window. An experimental setup of Mueller matrix polarimetry is built, and the samples are made by referring to the typical conical frustum windows in submersibles. By pressurizing different pressures on the samples, we can find the changes of their Mueller matrix images and further derived polarization parameters. The results show that the polarization parameters can characterize the stress transfer process and the elastic-plastic transformation process of the window under different pressurization pressures. We also use a two-layered wave plate model to simulate the stress distribution in the window, which reveals different performances of the former and latter layers of the window under pressurization. Finally, we use a finite element model to simulate and understand some of the above experimental results. This proposed method is expected to provide new possibilities for monitoring the window stress and further ensure the safety of deep manned submersibles.

Statistical Mueller matrix driven discrimination of suspended particles.

An effective method to calculate the statistical Mueller matrix (SMM) of suspended particles based on polarized light scattering is presented that takes advantage of the Stokes vectors measurement of individual particles. The calculation method of the SMM is derived based on statistics. Experimental results of Microcystis samples confirm that the SMM can characterize cells of different states. Then, pairwise contrast experiments indicate the great prospect of the SMM applied on the discrimination of suspended particles. It helps to find the optimal incident polarization state to discriminate suspended particles, and it has optimal discrimination ability. The parameter derived from the SMM can simultaneously discriminate particles including microalgae, microplastics, and sand-like particles.

Geometric optimization method for a polarization state generator of a Mueller matrix microscope.

We propose a geometric optimization method combined with the Coulombic energy indicator that can uniformly distribute N polarization states on the Poincaré sphere. Based on this method, we investigate the optimal frames of a rotating polarizer and rotating quarter-wave plate (RPRQ)-based polarization state generator (PSG) at different numbers of modulations. We use the PSG on a dual DoFP polarimeter-based Mueller matrix microscope to measure standard samples and pathological sections for testing the performance of an optimized RPRQ. The experimental results show that this method can effectively restrain noise and improve measurement accuracy.

Fast Mueller matrix microscope based on dual DoFP polarimeters.

In this Letter, we report a dual division of focal plane (DoFP) polarimeters-based full Mueller matrix microscope (DoFPs-MMM) for fast polarization imaging. Both acquisition speed and measurement accuracy are improved compared with those of a Mueller matrix microscope based on dual rotating retarders. Then, the system is applied to probe the polarization properties of a red blood cells smear. The experimental results show that a DoFPs-MMM has the potential to be a powerful tool for probing dynamic processes in living cells in future studies.

MuellerNet: a hybrid 3D-2D CNN for cell classification with Mueller matrix images.

Different from conventional microimaging techniques, polarization imaging can generate multiple polarization images in a single perspective by changing the polarization angle. However, how to efficiently fuse the information in these multiple polarization images by a convolutional neural network (CNN) is still a challenging problem. In this paper, we propose a hybrid 3D-2D convolutional neural network called MuellerNet, to classify biological cells with Mueller matrix images (MMIs). The MuellerNet includes a normal stream and a polarimetric stream, in which the first Mueller matrix image is taken as the input of normal stream, and the rest MMIs are stacked to form the input of a polarimetric stream. The normal stream is mainly constructed with a backbone network and, in the polarimetric stream, the attention mechanism is used to adaptively assign weights to different convolutional maps. To improve the network's discrimination, a loss function is introduced to simultaneously optimize parameters of the two streams. Two Mueller matrix image datasets are built, which include four types of breast cancer cells and three types of algal cells, respectively. Experiments are conducted on these two datasets with many well-known and recent networks. Results show that the proposed network efficiently improves the classification accuracy and helps to find discriminative features in MMIs.

Monitoring particulate composition changes during the flocculation process using polarized light scattering.

Monitoring the particulate composition changes during the flocculation process is still challenging for the research community. We use an experimental setup based on polarized light scattering to measure the polarization states of the scattered light of the individual particles. We build a classifier based on the support vector machine and feed it with the measured parameters. Results show that the classifier can effectively classify the particulate compositions, such as the sediment particles, flocculants, and flocs, which can be used to monitor the particulate composition changes during the flocculation process. Discussions on the intensity and polarization parameters find that the polarization parameters play a vital role in the classification of the particulate compositions in the flocculation suspensions. Additionally, the further analysis of the experimental data and the related simulations show that the degree of polarization can be an indicator of the flocculation process. We prove that the method based on polarized light scattering may be a potential in situ monitoring tool in the future for the study of the flocculation process.

Characterization of physiological states of the suspended marine microalgae using polarized light scattering: erratum.

This publisher's note corrects the author affiliations section of Appl. Opt.59, 1307 (2020)APOPAI0003-693510.1364/AO.377332.

Glomalin-related soil protein: The particle aggregation mechanism and its insight into coastal environment improvement.

Glomalin-related soil protein (GRSP), a ubiquitous microbial product, plays a crucial role in particle aggregation and metal adsorption, but the underlying mechanisms remain unknown. Here, GRSP fraction was extracted from estuarine ecosystems and systematically characterized to elucidate the aggregation mechanisms and its impact on coastal environment improvement. We found that GRSP fraction (gravimetric mass of extracted GRSP, 5.1-24.3 mg g-1) was a globally relevant novel bioflocculant and that protein (linked to Bradford protein assay, 1.64-4.37 mg g-1) was the active flocculant constituent. The zeta potential, FTIR, XPS, and 13C NMR analyses identified its key constituents and structure, and revealed that the charge neutralization and bridging were GRSP fraction aggregation mechanisms. Thermogravimetric-infrared spectrometry analysis showed that GRSP fraction was highly thermostable, and the main volatile pyrolysis products included H2O, CO2, CO, and CH4. The SEM-EDX and XPS Fe valence spectroscopy suggested that GRSP fraction contained rich Fe (11.91 ± 0.48%) and could form Fe-rich flocs with particles. We also found that GRSP fraction has a high adsorption capacity (76-95%) for Cu, Zn, Pb and Cd, and its flocculation properties provide new insights into metal adsorption. The analysis of particle aggregation mechanism and its metal adsorption capacity is of great significance to elucidate the role of GRSP fraction in coastal environment improvement.