Dredging wastewater discharge from shrimp ponds affects mangrove soil physical-chemical properties and enzyme activities.

Dredging wastewater discharge is a significant environmental concern for mariculture near mangrove ecosystems. However, little attention has been paid to its effects on the soil physical-chemical properties and enzyme activities in mangrove habitats. This study compared the soil physical-chemical properties and enzyme activities in the polluted area that received dredging wastewater from a shrimp pond with those in the control area without wastewater to explore the effects of wastewater discharge on the soil physical-chemical properties and enzyme activities. Variations in soil physical-chemical properties and enzyme activities across different tidal flat areas and depths were also examined. The polluted area exhibited lower soil salinity (10.47 ± 0.58 vs. 15.64 ± 0.54) and moisture content (41.85 ± 1.03 % vs. 45.81 ± 1.06 %) than the control area. Wastewater discharge increased soil enzyme activities, (acid phosphatase, protease, and catalase), resulting in higher inorganic nitrogen (13.20 ± 0.00 µg g-1 vs. 11.60 ± 0.03 µg g-1) but lower total nitrogen (0.93 ± 0.01 mg g-1 vs. 1.62 ± 0.11 mg g-1) in the contaminated zone. From the control to polluted area, there was an approximate increase of 0.43 and 0.83 mg g-1 in soil total phosphorus and soluble phosphate, driven by increased acid phosphatase. However, soil humus and organic matter decreased by 0.04 and 1.22 %, respectively, because of wastewater discharge. The impact of wastewater discharge on the soil physical-chemical properties and enzyme activities was most pronounced in the landward and surface soil layers (0-5 cm). The results showed that wastewater discharge altered soil physical-chemical properties and enzyme activities, accumulating soil bioavailable nutrients (inorganic nitrogen and soluble phosphate), but at the cost of reduced soil quality, especially organic matter, further adversely affecting the overall health of mangrove ecosystems. Prioritizing the management of wastewater discharged from mariculture adjacent to mangrove forests is crucial for mangrove conservation.

Functional neuroplasticity of facilitation and interference effects on inhibitory control following 3-month physical exercise in aging.

Preservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention; however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilitation and interference.

Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor.

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults.

BACKGROUND: Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). METHODS: We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing < 30%), both aged 45 years or younger, from 38 hospitals in China between 2017 and 2020. EOCAD patients who underwent successful percutaneous coronary intervention were followed for incident TLF. TyG index was defined as Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. We used logistic regression and Cox proportional hazards modeling to evaluate the association of TyG index with prevalent EOCAD and incident TLF, respectively. The discriminatory ability of TyG index was assessed by the area under the receiver-operating characteristic curve (AUC). RESULTS: Among the included 1513 EOCAD patients (39.6 ± 4.4 years, 95.4% male) and 1513 age-matched controls (39.0 ± 4.4 years, 46.4% male), TyG index was positively associated with the prevalence of EOCAD (adjusted odds ratio: 1.40, 95% confidence interval [CI] 1.23-1.60, per standard deviation [SD] increase in TyG index). The addition of TyG index to an empirical risk model provided an improvement in diagnostic ability for EOCAD, with a net reclassification improvement of 0.10 (95% CI 0.03-0.17, p = 0.005). During a medium of 33 month (IQR: 31-34 months) follow-up, 43 (3.3%) patients experienced TLF. Multivariate Cox regression model revealed that TyG index was an independent risk factor for TLF (adjusted hazard ratio [HR]: 2.410, 95% CI 1.07-5.42 comparing the top to bottom TyG index tertile groups; HR: 1.30, 95% CI 1.01-1.73, per SD increase in TyG index). Compared with a model of conventional risk factors alone, the addition of the TyG index modestly improved the AUC (0.722-0.734, p = 0.04) to predict TLF. CONCLUSIONS: TyG index is positively associated with prevalent EOCAD and incident TLF. TyG index appeared to be a valuable component of future efforts to improve CAD risk stratification and TLF outcome prediction among young adults.

A knowledge graph-based analytical model for mining clinical value of drug stress echocardiography for diagnosis, risk stratification and prognostic evaluation of coronary artery disease.

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice.

Revisiting the effects of exercise on cerebral neurovascular functions in rats using multimodal assessment techniques.

Physical activity in the form of aerobic exercise has many beneficial effects on brain function. Here, we aim to revisit the effects of exercise on brain morphology and neurovascular organization using a rat running model. Electrocorticography (ECoG) was integrated with laser speckle contrast imaging (LSCI) and applied to simultaneously detect CSD propagation and the corresponding neurovascular function. In addition, blood oxygenation level-dependent (BOLD) signal in fMRI was used to observe cerebral utilization of oxygen. Results showed significant decrease in somatosensory evoked potentials (SSEPs) and deceleration of CSD propagation in the EXE group. Western blot results in the EXE group showed significant increases in BDNF, GFAP, and NeuN levels and significant decreases in neurodegenerative disease markers. Decreases in SSEP and CSD parameters may result from exercise-induced increases in cerebrovascular system function and increases in the stability and buffering of extracellular ion concentrations and cortical excitability.

Prognostic Significance of Tumor-Infiltrating Lymphocytes Determined Using LinkNet on Colorectal Cancer Pathology Images.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have a significant prognostic value in cancers. However, very few automated, deep learning-based TIL scoring algorithms have been developed for colorectal cancer (CRC). MATERIALS AND METHODS: We developed an automated, multiscale LinkNet workflow for quantifying TILs at the cellular level in CRC tumors using H&E-stained images from the Lizard data set with annotations of lymphocytes. The predictive performance of the automatic TIL scores (TILsLink) for disease progression and overall survival (OS) was evaluated using two international data sets, including 554 patients with CRC from The Cancer Genome Atlas (TCGA) and 1,130 patients with CRC from Molecular and Cellular Oncology (MCO). RESULTS: The LinkNet model provided outstanding precision (0.9508), recall (0.9185), and overall F1 score (0.9347). Clear continuous TIL-hazard relationships were observed between TILsLink and the risk of disease progression or death in both TCGA and MCO cohorts. Both univariate and multivariate Cox regression analyses for the TCGA data demonstrated that patients with high TIL abundance had a significant (approximately 75%) reduction in risk for disease progression. In both the MCO and TCGA cohorts, the TIL-high group was significantly associated with improved OS in univariate analysis (30% and 54% reduction in risk, respectively). The favorable effects of high TIL levels were consistently observed in different subgroups (classified according to known risk factors). CONCLUSION: The proposed deep-learning workflow for automatic TIL quantification on the basis of LinkNet can be a useful tool for CRC. TILsLink is likely an independent risk factor for disease progression and carries predictive information of disease progression beyond the current clinical risk factors and biomarkers. The prognostic significance of TILsLink for OS is also evident.

Inactivated whole-virion SARS-CoV-2 vaccines and long-term clinical outcomes in patients with coronary atherosclerosis disease in China: a prospective cohort study.

AIMS: Publicized adverse events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concern among patients with coronary atherosclerosis disease (CAD). We sought to study the association between SARS-CoV-2 vaccines and long-term clinical outcomes including ischaemic and bleeding events among patients with CAD. METHODS AND RESULTS: Inpatients diagnosed with CAD by coronary angiography, without a history of SARS-CoV-2 infection and vaccination, were included between 1 January and 30 April 2021, and underwent follow-up until 31 January 2022. Two doses of inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, BBIBPCorV, or WIBP-CorV) were available after discharge, and the group was stratified by vaccination. The primary composite outcomes were cardiovascular death, non-fatal myocardial infarction, stent thrombosis, unplanned revascularization, ischaemic stroke, venous thrombo-embolism, or peripheral arterial thrombosis. The bleeding outcomes were Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Cox regression models with vaccination status as a time-dependent covariate were used to calculate the hazard ratio (HR) for the outcomes. A propensity score matching method was used to reduce confounding biases. This prospective cohort study included 2078 individuals with CAD, 1021 (49.1%) were vaccinated. During a median follow-up of 9.1 months, 45 (4.3%) primary composite outcomes occurred in the unvaccinated group, and 33 (3.2%) in the vaccinated group. In Cox regression, the adjusted HR was 1.13 [95% confidence interval (CI) 0.65-1.93]. The adjusted HR for the bleeding outcomes associated with vaccination was 0.81 [95% CI 0.35-1.19]. After matching, the adjusted HR for the primary composite outcomes associated with vaccination was 1.06 [95% CI 0.57-1.99] and for the bleeding outcomes was 0.91 [95% CI 0.35-2.38]. Similar results were found in the seven prespecified subgroups. No grade 3 adverse reactions after vaccination were recorded. CONCLUSION: Our results indicated no evidence of an increased ischaemic or bleeding risk after vaccination with inactivated SARS-CoV-2 vaccine among Chinese patients with CAD, with limited statistical power.

Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point-Blinded, Noninferiority Trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care after percutaneous coronary intervention. However, some adverse noncardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retaining the antithrombotic efficacy, but its combination with a P2Y12 inhibitor still lacks randomized clinical trial evidence. METHODS: In this randomized, open-label, noninferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100 mg twice a day plus clopidogrel 75 mg/d for 12 months) or conventional DAPT (aspirin 100 mg/d plus clopidogrel 75 mg/d for 12 months). The primary end point was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding. The end points were adjudicated by an independent Clinical Event Committee. RESULTS: Between January 11, 2018, and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary end point occurred in 101 patients (4.47%) in the indobufen-based DAPT group and 140 patients (6.11%) in the conventional DAPT group (absolute difference, -1.63%; Pnoninferiority<0.001; hazard ratio, 0.73 [95% CI, 0.56-0.94]; P=0.015). Cardiovascular death, nonfatal myocardial infarction, ischemic stroke, and stent thrombosis were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all P>0.05). The occurrence of Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding events was lower in the indobufen-based DAPT group compared with the conventional DAPT group (2.97% versus 4.71%; hazard ratio, 0.63 [95% CI, 0.46-0.85]; P=0.002), with the main decrease in type 2 bleeding (1.68% versus 3.49%; hazard ratio, 0.48 [95% CI, 0.33-0.70]; P<0.001). CONCLUSIONS: In Chinese patients with negative cardiac troponin undergoing drug-eluting stent implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was driven mainly by a reduction in bleeding events without an increase in ischemic events. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-IIR-17013505.

Improving cleaner production of human activities to mitigate total petroleum hydrocarbons accumulation in coastal environment.

The marine coast is an important ecological transitional boundary but easily suffers from human intervention. Total petroleum hydrocarbons (TPHs) are ubiquitous along the coast. However, the influence of anthropogenic and natural factors on TPHs distribution remains unclear. This study sampled surficial sediment (N = 243) from the coasts of the largest peninsula-Leizhou Peninsula, in Southern China. We found that land-based discharge, sea traffic, and sediment type significantly (p < 0.05) drive the accumulation of TPHs. We observed that TPHs increased by 1.036 µg · g-1 (exp[αi] = exp. [0.0355]) of its original value with the addition of one more boat on the wharf. Although the average TPHs were at a moderate level (124.68, ND-1536.14, µg · g-1) and risk, 'Blue Carbon' ecosystems, i.e., mangroves (224.84, ND - 1441.13, µg · g-1, p < 0.001) were more severely polluted. Cleaner production policy should be applied to mitigate TPHs discharging trend from coastal areas.

Mechanisms of Myocardial Damage Due to Hyperlipidemia: A Review of Recent Studies.

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.

Regulation of PD-L1 through direct binding of cholesterol to CRAC motifs.

Cholesterol, an essential molecule for cell structure, function, and viability, plays crucial roles in the development, progression, and survival of cancer cells. Earlier studies have shown that cholesterol-lowering drugs can inhibit the high expression of programmed-death ligand 1 (PD-L1) that contributes to immunoevasion in cancer cells. However, the regulatory mechanism of cell surface PD-L1 abundance by cholesterol is still controversial. Here, using nuclear magnetic resonance and biochemical techniques, we demonstrated that cholesterol can directly bind to the transmembrane domain of PD-L1 through two cholesterol-recognition amino acid consensus (CRAC) motifs, forming a sandwich-like architecture and stabilizing PD-L1 to prevent downstream degradation. Mutations at key binding residues prohibit PD-L1-cholesterol interactions, decreasing the cellular abundance of PD-L1. Our results reveal a unique regulatory mechanism that controls the stability of PD-L1 in cancer cells, providing an alternative method to overcome PD-L1-mediated immunoevasion in cancers.

FISH Mapping of Telomeric and Non-Telomeric (AG3T3)3 Reveal the Chromosome Numbers and Chromosome Rearrangements of 41 Woody Plants.

Data for the chromosomal FISH mapping localization of (AG3T3)3 are compiled for 37 species belonging 27 families; for 24 species and 14 families, this is the first such report. The chromosome number and length ranged from 14-136 and 0.56-14.48 µm, respectively. A total of 23 woody plants presented chromosome length less than 3 µm, thus belonging to the small chromosome group. Telomeric signals were observed at each chromosome terminus in 38 plants (90.5%) and were absent at several chromosome termini in only four woody plants (9.5%). Non-telomeric signals were observed in the chromosomes of 23 plants (54.8%); in particular, abundant non-telomeric (AG3T3)3 was obviously observed in Chimonanthus campanulatus. Telomeric signals outside of the chromosome were observed in 11 woody plants (26.2%). Overall, ten (AG3T3)3 signal pattern types were determined, indicating the complex genome architecture of the 37 considered species. The variation in signal pattern was likely due to chromosome deletion, duplication, inversion, and translocation. In addition, large primary constriction was observed in some species, probably due to or leading to chromosome breakage and the formation of new chromosomes. The presented results will guide further research focused on determining the chromosome number and disclosing chromosome rearrangements of woody plants.

How does bivalve size influence microplastics accumulation?

Microplastics (wasted plastic particles < 5 mm in diameter) are ubiquitously distributed in the marine environment. Filter-feeding and low trophic level bivalves are vulnerable to microplastics accumulation from the surrounding depositional environment, thereby threatening both ecological health and human food safety. Microplastics had been detected in lots of coastal Bivalvia species. However, the influence of biological morphology on the mechanism of microplastics accumulation is not clear. There is also a knowledge gap of which species are preferred for commercial consumption, which creates loopholes in risk identification for food safety. A survey on a commercial popular eaten but under-researched hard clam (Meretrix meretrix; Linnaeus, 1758) from a famous fishery port city in southern China was carried out to comprehensively analyze shell size influence on microplastics accumulation in bivalves and consequently, human intake risk via bivalve consumption. Detected microplastics count in per individual (MCI) was 24.64 ± 19.11 items · individual-1, and microplastics count per gram (MCG; wet weight with shell) was 0.66 ± 0.54 items · g-1. When the shell width grew by 1 mm, MCI increased by 1.01 times, but MCG decreased by 0.97 times. Dominant microplastics characteristics found in this study was fiber and fragment. Sizes ranged from 25 to 150 µm, and dark colors (black, red, and blue) were found. The mostly common polymers were polyethene (PE, 40%), polyethylene terephthalate (PET, 23%), and polypropylene (PP, 18%). Estimated annual intake (EAI) risk of microplastics via hard clam consumption by residents was 6652.26 ± 5327.28 items · year -1 · person -1. The microplastics in bivalves and EAI was relatively high. When shell width grew by 1 mm, EAI decreased by 0.97 times. Therefore, eating a fixed amount of larger hard clams with a relatively low amount of microplastics can reduce EAI risk for consumers. A systematic investigation of emission sources along main coast, where bivalve production is prominent will be useful for food safety control in this region.

Association Between Fatigue and Falls Risk Among the Elderly Aged Over 75 Years in China: The Chain Mediating Role of Falls Efficacy and Lower Limb Function.

Background: Although fatigue has been shown to be strongly associated with falls risk, very few studies have focused on its mechanism involved in community-dwelling older subjects. The purpose of this study was to explore the relationship between fatigue and falls risk and its internal mechanism by constructing a chain mediation model. Methods: A cross-sectional study design was adopted. A convenience sample of 270 older adults was recruited from July to October 2021 in an urban community, in Beijing, China. The participants completed the 14-item Fatigue Scale (FS-14), Falls Efficacy Scale International (FES-I), the Short Physical Performance Battery (SPPB) and Fall-Risk Self-Assessment Questionnaire (FRQ) to measure fatigue, falls efficacy, lower limb function and falls risk. The theory of unpleasant symptoms was used as a conceptual framework. Structural equation modeling (SEM) was utilized to test the hypothetical model. Results: The overall fit of final model was found to be satisfactory: χ2/df = 1.61, CFI = 0.971, TLI = 0.962, RMSEA = 0.049 (95% CI 0.030/0.066) and SRMR = 0.023. Fatigue had a direct effect on falls risk (ß = 0.559, S.E. = 0.089, 95% CI 0.380/0.731), and it also had indirect effects on falls risk (ß = 0.303, S.E. = 0.072, 95% CI 0.173/0.460) through mediating factors. Falls efficacy and lower limb function were the main mediating variables, and there was a chain mediating effect (ß = 0.015, S.E. = 0.010, 95% CI 0.003/0.046). Conclusions: Our study suggests that fatigue can influence falls risk among the elderly in China. There are many mediating paths between fatigue and falls risk. These results may help healthcare professionals to better understand the inherent relationship between fatigue and fall risk that may benefit older adults.

Development and Validation of a Novel Tool for the Prediction of Clopidogrel Response in Chinese Acute Coronary Syndrome Patients: The GeneFA Score.

Aim: Growing evidence indicated that CYP2C19 genotypes could only explain a fraction of the pharmacodynamic response to clopidogrel, while a number of clinical factors also have contributing roles. Our objective was to develop a new risk score to improve prognostication of ischemic events in Chinese patients treated with clopidogrel. Methods: A new risk score was developed and internally validated in 445 patients with acute coronary syndrome (ACS) undergoing coronary stenting. The final score was named the GeneFA score based on the inclusion of CYP2C19 genotype, fibrinogen, and age. External validation of the GeneFA score and comparison with the ABCD-GENE score were performed in an independent ACS cohort. Results: Based on the observed frequencies of high platelet reactivity (HRPR) in relation to the GeneFA risk score, a relatively higher clinical HRPR was observed in the upper quintile with a representative score of 3 (52.90%) and 4 (59.10%), whereas it was found less frequently in groups with scores 0 (6.70%), 1 (15.10%), and 2 (16.70%). Participants with a GeneFA score >2 had an increased risk of HRPR (54.3 vs. 14.7%, p < 0.001) and ischemic recurrence (20.7 vs. 5.4%, p < 0.001). The GeneFA score exhibited a better prediction for high HRPR patients as compared to the ABCD-GENE score (p < 0.001). In the validation population, GeneFA illustrated a similarly high prognostic value for HRPR incidence (C-statistic: 0.855 for GeneFA and 0.843 for ABCD-GENE) and ischemic recurrence (C-statistic: 0.726 for GeneFA and 0.724 for ABCD-GENE) on clopidogrel as compared to ABCD-GENE. Conclusion: The GeneFA risk score had a moderate predictive ability for HRPR on clopidogrel for CAD patients in Chinese populations. The predictive value of the GeneFA score was consistent with the ABCD-GENE score for HRPR identification.

Structural characterization of a dimerization interface in the CD28 transmembrane domain.

CD28 has a crucial role in regulating immune responses by enhancing T cell activation and differentiation. Recent studies have shown that the transmembrane helix (TMH) of CD28 mediates receptor assembly and activity, but a structural characterization of TMH is still lacking. Here, we determined the dimeric helix-helix packing of CD28-TMH using nuclear magnetic resonance (NMR) technology. Unexpectedly, wild-type CD28-TMH alone forms stable tetramers in lipid bicelles instead of dimers. The NMR structure of the CD28-TMH C165F mutant reveals that a GxxxA motif, which is highly conserved in many dimeric assemblies, is located at the dimerization interface. Mutating G160 and A164 can disrupt the transmembrane helix assembly and reduces CD28 enhancement in cells. In contrast, a previously proposed YxxxxT motif does not affect the dimerization of full-length CD28, but it does affect CD28 activity. These results imply that the transmembrane domain of CD28 regulates the signaling transduction in a complicated manner.

Construction of Konjac Glucomannan/Oxidized Hyaluronic Acid Hydrogels for Controlled Drug Release.

Konjac glucomannan (KGM) hydrogel has favorable gel-forming abilities, but its insufficient swelling capacity and poor control release characteristics limit its application. Therefore, in this study, oxidized hyaluronic acid (OHA) was used to improve the properties of KGM hydrogel. The influence of OHA on the structure and properties of KGM hydrogels was evaluated. The results show that the swelling capacity and rheological properties of the composite hydrogels increased with OHA concentration, which might be attributed to the hydrogen bond between the KGM and OHA, resulting in a compact three-dimensional gel network structure. Furthermore, epigallocatechin gallate (EGCG) was efficiently loaded into the KGM/OHA composite hydrogels and liberated in a sustained pattern. The cumulative EGCG release rate of the KGM/OHA hydrogels was enhanced by the increasing addition of OHA. The results show that the release rate of composite hydrogel can be controlled by the content of OHA. These results suggest that OHA has the potential to improve the properties and control release characteristics of KGM hydrogels.

Linking human activity to spatial accumulation of microplastics along mangrove coasts.

Microplastics (MP) in mangrove coasts are threating ecological health and seafood safety. However, quantitative evidence on the effects of different coastal human activities on microplastic accumulation in mangrove sediments is lacking, thereby impeding the policy development of evidence-based waste management. In this study, continuous geographical sampling (N = 50) was applied to collect sediments from the largest mangrove coast, namely the Leizhou Peninsula in China. Similar worldwide research data (16 mangrove coasts) were collected from the Science Citation Index Expanded (SCIE) database of the Web of Science. The connections between human drivers and microplastic accumulation were evaluated by spatial comparison, multi-correspondence analysis, and multiple differences analysis. The microplastic abundance fluctuated widely along the mangrove coasts (average value was 51.24, ranged from 6.40 to 255.57 items·kg-1 dry weight; coefficient of variation = 97%) with a globally lower-middle concentration in sediments of the Leizhou Peninsula. Densely populated urban residents and the floating population of tourists largely contributed to the high abundance of microplastics in mangrove sediments, of which large-sized (1-5 mm) white foams were the dominant type. Although suburbs had less crowds, both onshore and offshore fishery production could cause high accumulation of microplastics in neighboring mangrove coasts, which were characterized by small-sized (<1 mm) fragments with fresh color. Small microplastics (80%) with fresh color (44%) were dominant. Weathering may break down more toxic particles in urban areas neighboring mangrove coasts. Larger mangrove patches could partly block ocean-based microplastics; however, coasts surrounded by more geographical barriers had intensified pollutant accumulation. It was suggested that foam packaging of commodities for urban residents and tourists in popular tourism areas should be reduced and restrictions of fishery waste plastics are needed along shores with mangroves, especially in coasts surrounded by more geographic barriers.