Gradient Hydrogels Spatially Trapped Optical Cell Profiling for Quantitative Blood Cellular Osmotic Analysis.

The quantitative exploration of cellular osmotic responses and a thorough analysis of osmotic pressure-responsive cellular behaviors are poised to offer novel clinical insights into current research. This underscores a paradigm shift in the long-standing approach of colorimetric measurements triggered by red cell lysis. In this study, we engineered a purpose-driven optofluidic platform to facilitate the goal. Specifically, creating photocurable hydrogel traps surmounts a persistent challenge─optical signal interference from fluid disturbances. This achievement ensures a stable spatial phase of cells and the acquisition of optical signals for accurate osmotic response analysis at the single-cell level. Leveraging a multigradient microfluidic system, we constructed gradient osmotic hydrogel traps and developed an imaging recognition algorithm, empowering comprehensive analysis of cellular behaviors. Notably, this system has successfully and precisely analyzed individual and clustered cellular responses within the osmotic dimension. Prospective clinical testing has further substantiated its feasibility and performance in that it demonstrates an accuracy of 92% in discriminating complete hemolysis values (n = 25) and 100% in identifying initial hemolysis values (n = 25). Foreseeably, this strategy should promise to advance osmotic pressure-related cellular response analysis, benefiting further investigation and diagnosis of related blood diseases, blood quality, drug development, etc.

Effectiveness of family centred interventions for family caregivers: A systematic review and meta-analysis of randomized controlled trials.

AIMS AND OBJECTIVES: To examine the effectiveness of family-centred interventions among family caregivers. BACKGROUND: Family-centred interventions are an emerging form of intervention that can be effective at improving physical and mental health outcomes for patients and family caregivers. To date, no reviews have examined the effectiveness of family-centred interventions for family caregivers. DESIGN: A systematic review, including a meta-analysis, was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) checklist. METHODS: Seven English and two Chinese electronic databases were compressively searched from the outset to March 2023. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane 'Risk of bias assessment tool'. RESULTS: This systematic review and meta-analysis included 20 articles. The results of the meta-analysis showed that family-centred interventions could significantly improve caregiver burden (p=0.003), quality of life (p = 0.007), depression (p = 0.0002), and stress (p < 0.0001) but not anxiety or family functioning. According to our subgroup analysis, the family-centred empowerment model (p = 0.009) was superior to the other family intervention (p=0.004) in reducing caregiver burden. Family-centred interventions are more effective at reducing the burden of caregiving on family caregivers of adolescent patients (SMD=-0.79, 95% CI[-1.22,-0.36], p = 0.0003) than on adult patients (SMD=-0.37, 95% CI [-0.61,-0.12], p = 0.004). CONCLUSIONS: Family-centred interventions could enhance family caregivers' burden, quality of life, stress and depression but had no significant impact on anxiety or family functioning. RELEVANCE TO CLINICAL PRACTICE: Family-centred interventions have the potential to improve the health status and caregiving burden of family caregivers. Rigorous and high-quality evidence is needed to confirm the long-term effects of these interventions on family caregivers. TRIAL REGISTRATION DETAILS: The protocol has been registered in the PROSPERO international prospective register of systematic reviews (Protocol registration ID: CRD42023453607).

Functional characterization of D-type cyclins involved in cell division in rice.

BACKGROUND: D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. RESULTS: We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. CONCLUSIONS: The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

A microfluidic hemostatic diagnostics platform: Harnessing coagulation-induced adaptive-bubble behavioral perception.

Clinical viscoelastic hemostatic assays, which have been used for decades, rely on measuring biomechanical responses to physical stimuli but face challenges related to high device and test cost, limited portability, and limited scalability.. Here, we report a differential pattern using self-induced adaptive-bubble behavioral perception to refresh it. The adaptive behaviors of bubble deformation during coagulation precisely describe the transformation of viscoelastic hemostatic properties, being free of the precise and complex physical devices. And the integrated bubble array chip allows microassays and enables multi-bubble tests with good reproducibility. Recognition of the developed bubble behaviors empowers automated and user-friendly diagnosis. In a prospective clinical study (clinical model development [n = 273]; clinical assay [n = 44]), we show that the diagnostic accuracies were 99.1% for key viscoelastic hemostatic assay indicators (reaction time [R], kinetics time [K], alpha angle [Angle], maximum amplitude [MA], lysis at 30 min [LY30]; n = 220) and 100% (n = 44) for hypercoagulation, healthy, and hypocoagulation diagnoses. This should provide fresh insight into existing paradigms and help more clinical needs.

Biomimetic Compound Eyes with Gradient Ommatidium Arrays.

Compound eyes are high-performing natural optical perception systems with compact configurations, generating extensive research interest. Existing compound eye systems are often combinations of simple uniform microlens arrays; there are still challenges in making more ommatidia on the compound eye surface to focus to the same plane. Here, a biomimetic gradient compound eye is presented by artificially mimicking dragonflies. The multiple replication process efficiently endows compound eyes with the gradient characteristics of dragonfly compound eyes. Experimental results show that the manufactured compound eye allows multifocus imaging by virtue of the gradient ommatidium array arranged closely in a honeycomb pattern while ensuring excellent optical properties and compact configurations. Thousands of ommatidia showing a gradient trend at the millimeter scale while remaining relatively uniform at the micron scale have gradient focal lengths ranging from 260 to 450 µm. This gradient compound eye allows more ommatidia to focus on the same plane than traditional uniform compound eyes, which have experimentally been shown to capture more than 1100 in-plane clear images simultaneously, promising potential applications in micro-optical devices, optical imaging, and biochemical sensing.

Cognitive engagement of nursing undergraduates in blended learning: A parallel mixed method study.

BACKGROUND: Blended learning is being integrated into undergraduate nursing education at all levels and from all directions. Cognitive engagement is not only an embodiment and guarantee of students' engagement into the curriculum from a cognitive level, deep engagement and high-level thinking, but also an important indicator of whether students are effectively engaged in the blended learning curricula. However, no studies have been seen to investigate the cognitive engagement of nursing undergraduates in the blended learning curricula and its influential factors. OBJECTIVES: To explore nursing undergraduates' cognitive engagement during the blended learning curricula and its influential factors. DESIGN: A convergent parallel mixed-methods was used. Data were collected between November 2021 and May 2022, inclusive. SETTINGS AND PARTICIPANTS: The study was carried out in the nursing school at a university in China. Participants including students undertaking entry to the blended learning curricula. METHODS: In the quantitative component (n = 142), participants' cognitive engagement was investigated and factors associated with it were examined using univariate analysis, correlation analysis and multiple regression analysis. During this period, personal, semi-structured interviews were conducted with a subset of these participants (n = 15) to understand participants' cognitive engagement experiences. RESULTS: The cognitive engagement of nursing undergraduates was at a moderate level and the cognitive engagement experiences were reflected in the four themes of Reconstitution, Connection, Elaboration and Retention. The influential factors of cognitive engagement were learning activities (ß = 0.226, p = 0.004), autonomy (ß = 0.158, p = 0.047), academic self-efficacy (ß = 0.311, p < 0.001, ß = 0.271, p < 0.001) and social interaction (ß = 0.358, p < 0.001). CONCLUSIONS: The cognitive engagement of nursing undergraduates in the blended learning curricula needs to be improved. To maximize promote cognitive engagement of nursing undergraduates in the blended learning curricula, educators should design diverse learning activities, engage in high quality social interactions with students, and maximize students' autonomy and self-efficacy.

Confinement-enhanced microalgal individuals biosensing for digital atrazine assay.

Microalgal sensors are widely recognized for their high sensitivity, accessibility, and low cost. However, the current dilemma of motion-induced spatial phase changes and concentration-related multiple scattering interferes with induced test instability and limited sensitivity, which has hindered their practical applications. Here, a differentiated strategy, named confinement-enhanced microalgal biosensing (C-EMB), is developed and proposed to pave the way. The in-situ printed microgel trap is designed to confine Chlamydomonas reinhardtii individuals, stabilizing their spatial phase. The microgel trap arrays are introduced to eliminate the multiple scattering of microalgae, breaking the existing effective concentration in traditional microalgal sensing and enabling sensitive assays. The integration with lab-on-a-chip technology and a developed digital imaging algorithm empower portable and automated detection. With this system, a microalgae analyzer is developed for atrazine detection, featuring a linear range of 0.04-100 µg/L. We assess the system's performance through practical atrazine assays on commercial food, using a double-blind test against a standard instrument. Our results demonstrate the good accuracy and test stability of this system with the mean bias atrazine detection in corn and sugarcane juice samples (SD) were 1.661 µg/L (3.122 µg/L) and 3.144 µg/L (4.125 µg/L), respectively. This method provides a new paradigm of microalgal sensors and should advance the further applications of microalgal sensors in commercial and practical settings.

Effectiveness of Internet-Based Cognitive Behavioral Therapy for Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Internet-based cognitive behavioral therapy (ICBT) is a relatively new therapy with unknown effectiveness in patients with cancer. In addition, therapist-guided and self-guided ICBT patient-specific outcomes for cancer patients remain to be explored. OBJECTIVE: To explore the effects of ICBT on psychological outcomes, physical outcomes, and daily life outcomes in patients with cancer. METHODS: Electronic databases such as PubMed, Web of Science, Cochrane Library, EMBASE, APA PsycINFO, ProQuest, and ClinicalTrials.gov were searched for relevant studies published from their inception to October 2022. Five GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) considerations were used to assess the quality of relevant evidence. Data analysis was performed via RevMan 5.4 (The Cochrane Collaboration, London, United Kingdom) and Stata 15.0 (StataCorp, College Station, Texas). RESULTS: Three thousand two hundred forty-nine participants from 20 studies were included in the meta-analysis. Statistically significant effects of ICBT were found on psychological distress, quality of life (QOL), anxiety, and depression, after the intervention. A separate analysis of follow-up data showed that ICBT had a sustainable effect on psychological distress, anxiety, and depression. Subgroup analyses showed that therapist-guided ICBT was more effective for psychological distress and QOL. CONCLUSION: Internet-based cognitive behavioral therapy can improve symptom management for patients with cancer. IMPLICATIONS FOR PRACTICE: Internet-based cognitive behavioral therapy effectively improves psychological distress, anxiety, and depression in patients with cancer after intervention and at follow-up. Internet-based cognitive behavioral therapy improved QOL for cancer patients postintervention but not during follow-up. Internet-based cognitive behavioral therapy did not relieve fatigue or fear of recurrence in cancer patients. Therapist-guided ICBT is recommended for its superior outcomes in alleviating psychological distress and improving overall QOL in adults with cancer when compared with self-guided ICBT.

Valve-Adjustable Optofluidic Bio-Imaging Platform for Progressive Stenosis Investigation.

The clinical evidence has proven that valvular stenosis is closely related to many vascular diseases, which attracts great academic attention to the corresponding pathological mechanisms. The investigation is expected to benefit from the further development of an in vitro model that is tunable for bio-mimicking progressive valvular stenosis and enables accurate optical recognition in complex blood flow. Here, we develop a valve-adjustable optofluidic bio-imaging recognition platform to fulfill it. Specifically, the bionic valve was designed with in situ soft membrane, and the internal air-pressure chamber could be regulated from the inside out to bio-mimic progressive valvular stenosis. The developed imaging algorithm enhances the recognition of optical details in blood flow imaging and allows for quantitative analysis. In a prospective clinical study, we examined the effect of progressive valvular stenosis on hemodynamics within the typical physiological range of veins by this way, where the inhomogeneity and local enhancement effect in the altered blood flow field were precisely described and the optical differences were quantified. The effectiveness and consistency of the results were further validated through statistical analysis. In addition, we tested it on fluorescence and noticed its good performance in fluorescent tracing of the clotting process. In virtue of theses merits, this system should be able to contribute to mechanism investigation, pharmaceutical development, and therapeutics of valvular stenosis-related diseases.

ALBINO EMBRYO AND SEEDLING is required for RNA splicing and chloroplast homeostasis in Arabidopsis.

Pentatricopeptide repeat (PPR) proteins form a large protein family and have diverse functions in plant development. Here, we identified an ALBINO EMBRYO AND SEEDLING (AES) gene that encodes a P-type PPR protein expressed in various tissues, especially the young leaves of Arabidopsis (Arabidopsis thaliana). Its null mutant aes exhibited a collapsed chloroplast membrane system, reduced pigment content and photosynthetic activity, decreased transcript levels of PEP (plastid-encoded polymerase)-dependent chloroplast genes, and defective RNA splicing. Further work revealed that AES could directly bind to psbB-psbT, psbH-petB, rps8-rpl36, clpP, ycf3, and ndhA in vivo and in vitro and that the splicing efficiencies of these genes and the expression levels of ycf3, ndhA, and cis-tron psbB-psbT-psbH-petB-petD decreased dramatically, leading to defective PSI, PSII, and Cyt b6f in aes. Moreover, AES could be transported into the chloroplast stroma via the TOC-TIC channel with the assistance of Tic110 and cpSRP54 and may recruit HCF244, SOT1, and CAF1 to participate in the target RNA process. These findings suggested that AES is an essential protein for the assembly of photosynthetic complexes, providing insights into the splicing of psbB operon (psbB-psbT-psbH-petB-petD), ycf3, and ndhA, as well as maintaining chloroplast homeostasis.

Cognitive appraisal of health and its influencing factors among pregnant women with gestational diabetes mellitus: A cross-sectional study.

AIM: To investigate the status quo of cognitive appraisal of health and its influencing factors among pregnant women with gestational diabetes mellitus. METHODS: A cross-sectional survey was conducted from June 2020 to November 2020. Participants were recruited from a tertiary hospital by a convenient sample method. A total of 300 pregnant women with gestational diabetes mellitus completed the survey, including self-compiled individual information questionnaire, Cognitive Appraisal of Health Scale, Pregnancy Stress Rating Scale and General Self-Efficacy Scale. RESULTS: For cognitive appraisal of health, the median score of challenge dimension was 3.75 (3.50, 4.00), benign/irrelevant was 2.75 (2.00, 3.50), harm/loss was 2.38 (2.00, 3.00) and threat was 2.40 (2.00, 2.80), respectively. Regression analyses showed that gestational age, mode of conception, history of abortion, insulin usage, pregnancy stress and self-efficacy were the predictors of cognitive appraisal of health. CONCLUSIONS: This study revealed that pregnant women with gestational diabetes mellitus tended to make positive cognitive appraisal of health. And healthcare providers need to make full use of their predictors of cognitive appraisal of health to improve cognitive appraisal to manage stress and ameliorate pregnancy outcomes.

Magnetically Actuated Hydrogel Stamping-Assisted Cellular Mechanical Analyzer for Stored Blood Quality Detection.

Cellular mechanical property analysis reflecting the physiological and pathological states of cells plays a crucial role in assessing the quality of stored blood. However, its complex equipment needs, operation difficulty, and clogging issues hinder automated and rapid biomechanical testing. Here, we propose a promising biosensor assisted by magnetically actuated hydrogel stamping to fulfill it. The flexible magnetic actuator triggers the collective deformation of multiple cells in the light-cured hydrogel, and it allows for on-demand bioforce stimulation with the advantages of portability, cost-effectiveness, and simplicity of operation. The magnetically manipulated cell deformation processes are captured by the integrated miniaturized optical imaging system, and the cellular mechanical property parameters are extracted from the captured images for real-time analysis and intelligent sensing. In this work, 30 clinical blood samples with different storage durations (<14 days and >14 days) were tested. A deviation of 3.3% in the differentiation of blood storage durations by this system compared to physician annotation demonstrated its feasibility. This system should broaden the application of cellular mechanical assays in diverse clinical settings.

Convenient tumor 3D spheroid arrays manufacturing via acoustic excited bubbles for in situ drug screening.

The quick and convenient fabrication of in vitro tumor spheroids models has been pursued for clinical drug discovery and personalized therapy. Here, uniform three-dimensional (3D) tumor spheroids are quickly constructed by acoustically excited bubble arrays in a microfluidic chip and performed drug response testing in situ. In detail, bubble oscillation excited by acoustic waves induces second radiation force, resulting in the cells rotating and aggregating into tumor spheroids, which obtain controllable sizes ranging from 30 to 300 µm. These spherical tumor models are located in microfluidic networks, where drug solutions with gradient concentrations are generated from 0 to 18 mg mL-1, so that the cell spheroids response to drugs can be monitored conveniently and efficiently. This one-step tumor spheroids manufacturing method significantly reduces the model construction time to less than 15 s and increases efficiency by eliminating additional transfer processes. These significant advantages of convenience and high-throughput manufacturing make the tumor models promising for use in tumor treatment and point-of-care diagnosis.

Effects of decision aids on breast reconstruction: A systematic review and meta-analysis of randomised controlled trials.

AIMS AND OBJECTIVES: To systematically evaluate the effects of decision aids for women facing breast reconstruction decision on decision conflict, decision regret, knowledge, satisfaction, anxiety and depression. BACKGROUND: Breast reconstruction decision is not good or bad and should be guided by clinical evidence and patient preferences. Decision aids can increase the patient's decision-making enthusiasm and ability, improve the quality of decision and promote shared decision-making between patients and medical staff. DESIGN: Systematic review and meta-analysis. METHODS: Eight databases were conducted from the establishment of the database until October 2021. The PRISMA checklist was selected for analysis in this paper. The meta-analysis was conducted in Review Manager 5.3. The quality of the studies was assessed using the Cochrane risk-of-bias tool. The result is decision conflict, decision regret, knowledge and other secondary outcomes. Sensitivity analysis and subgroup analysis were also conducted. RESULTS: A total of twelve randomised controlled trials (RCTs) were included in the systematic review and meta-analysis. Meta-analysis revealed that decision aids could significantly reduce decision conflict and decision regret, improve knowledge, satisfaction and depression and had no influence on anxiety. CONCLUSIONS: The results of the systematic review and meta-analysis reviewed the positive effect of decision aids on the decision-making of women facing postmastectomy breast reconstruction. In the future, more well-designed RCTs are needed to confirm the effects of decision aids on the decision-making of breast reconstruction and nurses should be encouraged to take part in the development of decision aids in accordance with strict standards and apply them to breast cancer patients considering postmastectomy breast reconstruction. RELEVANCE TO CLINICAL PRACTICE: Our study provides evidence for the effectiveness of decision aids on breast reconstruction and points to the important role of healthcare providers in the use of decision aids and in facilitating shared decision-making.

The effectiveness of auricular acupressure on pain management during labor: A systematic review and meta-analysis of randomized controlled trials.

AIM: This meta-analysis aimed to systematically evaluate the effectiveness of auricular acupressure on pain management during labor. METHODS: Six English and three Chinese electronic databases were comprehensively searched from inception to 6 November 2021. The PRISMA checklist was followed. The methodological quality of the included studies was assessed with the Cochrane Collaboration Bias Risk Assessment Tool. The meta-analysis was performed using Review Manager 5.3 software. Heterogeneity between studies was calculated using I2 . RESULTS: Five studies comprising 312 participants were included. The labor pain scores of the auricular acupressure group were significantly lower than those of the usual care group at cervix dilations of 6, 8, and 10 cm, with mean differences (95% confidence intervals) of -1.05 (-1.41, -0.69), -1.44 (-2.07, -0.82), and -1.96 (-3.30, -0.61), respectively. Auricular acupressure can thus effectively improve the labor pain perception at cervix dilations of 6, 8, and 10 cm. Moreover, auricular acupressure shortened the active phase, and had the trend of shortening the second and third stages of labor. There was no evidence that auricular acupressure had an effect on the rate of cesarean section or the 1 and 5 min Apgar scores. CONCLUSION: Effective labor pain relief, better labor pain perception, and the lack of adverse effects support the use of auricular acupressure. More high-quality and rigorous trials are needed to verify our findings before we can make strong recommendations.

The gut microbiota diversity of five Orthoptera (Insecta, Polyneoptera) insects determined by DNA metabarcoding.

Most orthopteran insects are phytophagous and some are important pests in agriculture and forests. Many intestinal microflora of Orthoptera insects have been reported, primarily from Acridoidea and there have been few reports of other taxa. In this study, we collected 15 individuals representing five species (Ruspolialineosa, Tetrixjaponica, Erianthusversicolor, Gryllotalpaorientalis and Teleogryllusemma) belonging to five orthopteran superfamilies (Tettigonioidea, Tetrigoidea, Eumastacoidea, Gryllotalpoidea and Grylloidea) to characterise and compare the gut microbiota with greater taxonomic width by performing sequencing analysis of the 16S rRNA V4 region in gut material. A total of 606,053 high-quality sequences and 3,105 OTUs were acquired from 15 gut samples representing 24 phyla, 48 classes, 69 orders, 133 families and 219 genera. Firmicutes and bacteria were the most abundant phyla, followed by Bacteroidetes, Cyanobacteria, Actinobacteria and Acidobacteria. At the genus level, Serratia, Citrobacter, Wolbachia, Lactobacillus and Parabacteroides were the most predominant genera in R.lineosa, T.japonica, E.versicolor, G.orientalis and T.emma, respectively. Both Principal Coordinates Analysis (PCoA) and heatmap results revealed significant differences in bacterial community composition across species. Additionally, alpha diversity analysis indicated the bacterial richness was significantly different amongst the five species.

Space-time-regulated imaging analyzer for smart coagulation diagnosis.

The development of intelligent blood coagulation diagnoses is awaited to meet the current need for large clinical time-sensitive caseloads due to its efficient and automated diagnoses. Herein, a method is reported and validated to realize it through artificial intelligence (AI)-assisted optical clotting biophysics (OCB) properties identification. The image differential calculation is used for precise acquisition of OCB properties with elimination of initial differences, and the strategy of space-time regulation allows on-demand space time OCB properties identification and enables diverse blood function diagnoses. The integrated applications of smartphones and cloud computing offer a user-friendly automated analysis for accurate and convenient diagnoses. The prospective assays of clinical cases (n = 41) show that the system realizes 97.6%, 95.1%, and 100% accuracy for coagulation factors, fibrinogen function, and comprehensive blood coagulation diagnoses, respectively. This method should enable more low-cost and convenient diagnoses and provide a path for potential diagnostic-markers finding.

ANGPTL8 is a negative regulator in pathological cardiac hypertrophy.

Pathological cardiac hypertrophy is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the role of angiopoietin-like protein 8 (ANGPTL8) in pathological cardiac hypertrophy. We found that serum ANGPTL8 levels were significantly increased in hypertensive patients with cardiac hypertrophy and in mice with cardiac hypertrophy induced by Ang II or TAC. Furthermore, the secretion of ANGPTL8 from the liver was increased during hypertrophic processes, which were triggered by Ang II. In the Ang II- and transverse aortic constriction (TAC)-induced mouse cardiac hypertrophy model, ANGPTL8 deficiency remarkably accelerated cardiac hypertrophy and fibrosis with deteriorating cardiac dysfunction. Accordingly, both recombinant human full-length ANGPTL8 (rANGPTL8) protein and ANGPTL8 overexpression significantly mitigated Ang II-induced cell enlargement in primary neonatal rat cardiomyocytes (NRCMs) and H9c2 cells. Mechanistically, the antihypertrophic effects of ANGPTL8 depended on inhibiting Akt and GSK-3ß activation, and the Akt activator SC-79 abolished the antihypertrophic effects of rANGPTL8 in vitro. Moreover, we demonstrated that ANGPTL8 directly bound to the paired Ig-like receptor PIRB (LILRB3) by RNA-seq and immunoprecipitation-mass screening. Remarkably, the antihypertrophic effects of ANGPTL8 were largely blocked by anti-LILRB3 and siRNA-LILRB3. Our study indicated that ANGPTL8 served as a novel negative regulator of pathological cardiac hypertrophy by binding to LILRB3 (PIRB) and inhibiting Akt/GSK3ß activation, suggesting that ANGPTL8 may provide synergistic effects in combination with AT1 blockers and become a therapeutic target for cardiac hypertrophy and heart failure.

Microfluidic-based in vitro thrombosis model for studying microplastics toxicity.

The potential impact of microplastics (MPs) on health has caused great concern, and a toxicology platform that realistically reproduces the system behaviour is urgently needed to further explore and validate MP-related health issues. Herein, we introduce an optically assisted thrombus platform to reveal the interaction of MPs with the vascular system. The risk of accumulation has also been evaluated using a mouse model, and the effect of MPs on the properties of the thrombus are validated via in vitro experiments. The microfluidic system is endothelialized, and the regional tissue injury-induced thrombosis is then realized through optical irradiation. Whole blood is perfused with MPs, and the invasion process visualized and recorded. The mouse model shows a cumulative risk in the blood with continuous exposure to MPs (P-value < 0.0001). The on-chip results show that MP invasion leads to decreased binding of fibrin to platelets (P-value < 0.0001), which is consistent with the results of the in vitro experiments, and shows a high risk of thrombus shedding in real blood flow compared with normal thrombus. This work provides a new method to further reveal MP-related health risks.

Phosphatidylserine released from apoptotic cells in tumor induces M2-like macrophage polarization through the PSR-STAT3-JMJD3 axis.

BACKGROUND: Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. METHODS: Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. RESULTS: The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. CONCLUSIONS: This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.