Mitigation of Stress-induced Structural Remodeling and Functional Deficiency in iPSC-CMs with PLN R9C Mutation by Promoting Autophagy.

Background: Phospholamban (PLN) is a key regulator of cardiac function connecting adrenergic signaling and calcium homeostasis. The R9C mutation of PLN is known to cause early onset dilated cardiomyopathy (DCM) and premature death, yet the detailed mechanisms underlie the pathologic remodeling process are not well defined in human cardiomyocytes. The aim of this study is to unravel the role of PLN R9C in DCM and identify potential therapeutic targets. Methods: PLN R9C knock-in (KI) and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated and comprehensively examined for their expression profile, contractile function, and cellular signaling under both baseline conditions and following functional challenges. Results: PLN R9C KI iPSC-CMs exhibited near-normal morphology and calcium handling, slightly increased contractility, and an attenuated response to ß-adrenergic activation compared to wild-type (WT) cells. However, treatment with a maturation medium (MM) has induced fundamentally different remodeling in the two groups: while it improved the structural integrity and functional performance of WT cells, the same treatment result in sarcomere disarrangement, calcium handling deficiency, and further disrupted adrenergic signaling in PLN R9C KI cells. To understand the mechanism, transcriptomic analysis showed the enrichment of protein homeostasis signaling pathways specifically in PLN R9C KI cells in response to the MM treatment and increased contractile demands. Further studies also indicated elevated ROS levels, interrupted autophagic flux, and increased pentamer PLN aggregation in functionally challenged KI cells. These results were further confirmed in patient-specific iPSC-CM models, suggesting that functional stresses exacerbate the deficiencies in PLN R9C cells through disrupting protein homeostasis. Indeed, treating stressed patient cells with autophagy-accelerating reagents, such as metformin and rapamycin, has restored autophagic flux, mitigated sarcomere disarrangement, and partially rescued ß-adrenergic signaling and cardiac function. Conclusions: PLN R9C leads to a mild increase of calcium recycling and contractility. Functional challenges further enhanced contractile and proteostasis stress, leading to autophagic overload, structural remodeling, and functional deficiencies in PLN R9C cardiomyocytes. Activation of autophagy signaling partially rescues these effects, revealing a potential therapeutic target for DCM patients with the PLN R9C mutation. Graphic abstracts: A graphic abstract is available for this article.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

Reconfigurable perovskite X-ray detector for intelligent imaging.

X-ray detection is widely used in various applications. However, to meet the demand for high image quality and high accuracy diagnosis, the raw data increases and imposes challenges for conventional X-ray detection hardware regarding data transmission and power consumption. To tackle these issues, we present a scheme of in-X-ray-detector computing based on CsPbBr3 single-crystal detector with convenient polarity reconfigurability, good linear dynamic range, and robust stability. The detector features a stable trap-free device structure and achieves a high linear dynamic range of 106 dB. As a result, the detector could achieve edge extraction imaging with a data compression ratio of ~50%, and could also be programmed and trained to perform pattern recognition tasks with a high accuracy of 100%. Our research shows that in-X-ray-detector computing can be used in flexible and complex scenarios, making it a promising platform for intelligent X-ray imaging.

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Tissue-specific toxic effects of nano-copper on zebrafish.

Understanding the behavior and potential toxicity of copper nanoparticles (nano-Cu) in the aquatic environment is a primary way to assess their environmental risks. In this study, RNA-seq was performed on three different tissues (gills, intestines, and muscles) of zebrafish exposed to nano-Cu, to explore the potential toxic mechanism of nano-Cu on zebrafish. The results indicated that the toxic mechanism of nano-Cu on zebrafish was tissue-specific. Nano-Cu enables the CB1 receptor of the presynaptic membrane of gill cells to affect short-term synaptic plasticity or long-term synaptic changes (ECB-LTD) through DSI and DSE, causing dysfunction of intercellular signal transmission. Imbalance of de novo synthesis of UMP in intestinal cells and its transformation to UDP, UTP, uridine, and uracil, resulted in many functions involved in the pyrimidine metabolic pathway being blocked. Meanwhile, the toxicity of nano-Cu caused abnormal expression of RAD51 gene in muscle cells, which affects the repair of damaged DNA through Fanconi anemia and homologous recombination pathway, thus causing cell cycle disorder. These results provide insights for us to better understand the differences in toxicity of nano-Cu on zebrafish tissues and are helpful for a comprehensive assessment of nano-Cu's effects on aquatic organisms.

A critical review on BDE-209: Source, distribution, influencing factors, toxicity, and degradation.

As the most widely used polybrominated diphenyl ether, BDE-209 is commonly used in polymer-based commercial and household products. Due to its unique physicochemical properties, BDE-209 is ubiquitous in a variety of environmental compartments and can be exposed to organisms in various ways and cause toxic effects. The present review outlines the current state of knowledge on the occurrence of BDE-209 in the environment, influencing factors, toxicity, and degradation. BDE-209 has been detected in various environmental matrices including air, soil, water, and sediment. Additionally, environmental factors such as organic matter, total suspended particulate, hydrodynamic, wind, and temperature affecting BDE-209 are specifically discussed. Toxicity studies suggest BDE-209 may cause systemic toxic effects on living organisms, reproductive toxicity, embryo-fetal toxicity, genetic toxicity, endocrine toxicity, neurotoxicity, immunotoxicity, and developmental toxicity, or even be carcinogenic. BDE-209 has toxic effects on organisms mainly through epigenetic regulation and induction of oxidative stress. Evidence regarding the degradation of BDE-209, including biodegradation, photodegradation, Fenton degradation, zero-valent iron degradation, chemical oxidative degradation, and microwave radiation degradation is summarized. This review may contribute to assessing the environmental risks of BDE-209 to help develop rational management plans.

Long non-coding RNA LHX1-DT regulates cardiomyocyte differentiation through H2A.Z-mediated LHX1 transcriptional activation.

Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called LHX1-DT, which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene. Our findings demonstrated that LHX1-DT is nuclear-localized and transiently elevated expression along with LHX1 during early differentiation of cardiomyocytes. The phenotype was rescued by overexpression of LHX1 into the LHX1-DT-/- hESCs, indicating LHX1 is the downstream of LHX1-DT. Mechanistically, we discovered that LHX1-DT physically interacted with RNA/histone-binding protein PHF6 during mesoderm commitment and efficiently replaced conventional histone H2A with a histone variant H2A.Z at the promoter region of LHX1. In summary, our work uncovers a novel lncRNA, LHX1-DT, which plays a vital role in mediating the exchange of histone variants H2A.Z and H2A at the promoter region of LHX1.

Rheological engineering of perovskite suspension toward high-resolution X-ray flat-panel detector.

Solution-processed polycrystalline perovskite film is promising for the next generation X-ray imaging. However, the spatial resolution of current perovskite X-ray panel detectors is far lower than the theoretical limit. Herein we find that the pixel level non-uniformity, also known as fixed pattern noise, is the chief culprit affecting the signal-to-noise ratio and reducing the resolution of perovskite detectors. We report a synergistic strategy of rheological engineering the perovskite suspensions to achieve X-ray flat panel detectors with pixel-level high uniformity and near-to-limit spatial resolution. Our approach includes the addition of methylammonium iodide and polyacrylonitrile to the perovskite suspension, to synergistically enhance the flowability and particle stability of the oversaturated solution. The obtained suspension perfectly suits for the blade-coating process, avoiding the uneven distribution of solutes and particles within perovskite films. The assembled perovskite panel detector exhibits greatly improved fixed pattern noise value (1.39%), high sensitivity (2.24 × 104 µC Gyair-1 cm-2), low detection limit (28.57 nGyair·s-1) as well as good working stability, close to the performance of single crystal detectors. Moreover, the detector achieves a near-to-limit resolution of 0.51 lp/pix.

One-dimensional scintillator film with benign grain boundaries for high-resolution and fast x-ray imaging.

Fast and high-resolution x-ray imaging demands scintillator films with negligible afterglow, high scintillation yield, and minimized cross-talk. However, grain boundaries (GBs) are abundant in polycrystalline scintillator film, and, for current inorganic scintillators, detrimental dangling bonds at GBs inevitably extend radioluminescence lifetime and increase nonradiative recombination loss, deteriorating afterglow and scintillation yield. Here, we demonstrate that scintillators with one-dimensional (1D) crystal structure, Cs5Cu3Cl6I2 explored here, possess benign GBs without dangling bonds, yielding nearly identical afterglow and scintillation yield for single crystals and polycrystalline films. Because of its 1D crystal structure, Cs5Cu3Cl6I2 films with desired columnar morphology are easily obtained via close space sublimation, exhibit negligible afterglow (0.1% at 10 ms) and high scintillation yield (1.2 times of CsI:Tl). We have also demonstrated fast x-ray imaging with 27 line pairs mm-1 resolution and frame rate up to 33 fps, surpassing most existing scintillators. We believe that the 1D scintillators can greatly boost x-ray imaging performance.

An effector of 'Candidatus Liberibacter asiaticus' manipulates autophagy to promote bacterial infection.

Autophagy functions in plant host immunity responses to pathogen infection. The molecular mechanisms and functions used by the citrus Huanglongbing (HLB)-associated intracellular bacterium 'Candidatus Liberibacter asiaticus' (CLas) to manipulate autophagy are unknown. We identified a CLas effector, SDE4405 (CLIBASIA_04405), which contributes to HLB progression. 'Wanjincheng' orange (Citrus sinensis) transgenic plants expressing SDE4405 promotes CLas proliferation and symptom expression via suppressing host immunity responses. SDE4405 interacts with the ATG8-family of proteins (ATG8s), and their interactions activate autophagy in Nicotiana benthamiana. The occurrence of autophagy is also significantly enhanced in SDE4405-transgenic citrus plants. Interrupting NbATG8s-SDE4405 interaction by silencing of NbATG8c reduces Pseudomonas syringae pv. tomato strain DC3000ΔhopQ1-1 (Pst DC3000ΔhopQ1-1) proliferation in N. benthamiana, and transient overexpression of CsATG8c and SDE4405 in citrus promotes Xanthomonas citri subsp. citri (Xcc) multiplication, suggesting that SDE4405-ATG8s interaction negatively regulates plant defense. These results demonstrate the role of the CLas effector protein in manipulating autophagy, and provide new molecular insights into the interaction between CLas and citrus hosts.

Self-wavelength shifting in two-dimensional perovskite for sensitive and fast gamma-ray detection.

Lead halide perovskites have recently emerged as promising X/γ-ray scintillators. However, the small Stokes shift of exciton luminescence in perovskite scintillators creates problems for the light extraction efficiency and severely impedes their applications in hard X/γ-ray detection. Dopants have been used to shift the emission wavelength, but the radioluminescence lifetime has also been unwantedly extended. Herein, we demonstrate the intrinsic strain in 2D perovskite crystals as a general phenomenon, which could be utilized as self-wavelength shifting to reduce the self-absorption effect without sacrificing the radiation response speed. Furthermore, we successfully demonstrated the first imaging reconstruction by perovskites for application of positron emission tomography. The coincidence time resolution for the optimized perovskite single crystals (4 × 4 × 0.8 mm3) reached 119 ± 3 ps. This work provides a new paradigm for suppressing the self-absorption effect in scintillators and may facilitate the application of perovskite scintillators in practical hard X/γ-ray detections.

Solution-Processed Hybrid Europium (II) Iodide Scintillator for Sensitive X-Ray Detection.

Lead halide perovskite nanocrystals have recently demonstrated great potential as x-ray scintillators, yet they still suffer toxicity issues, inferior light yield (LY) caused by severe self-absorption. Nontoxic bivalent europium ions (Eu2+) with intrinsically efficient and self-absorption-free d-f transition are a prospective replacement for the toxic Pb2+. Here, we demonstrated solution-processed organic-inorganic hybrid halide BA10EuI12 (BA denotes C4H9NH4+) single crystals for the first time. BA10EuI12 was crystallized in a monoclinic space group of P21/c, with photoactive sites of [EuI6]4- octahedra isolated by BA+ cations, which exhibited high photoluminescence quantum yield of 72.5% and large Stokes shift of 97 nm. These properties enable an appreciable LY value of 79.6% of LYSO (equivalent to ~27,000 photons per MeV) for BA10EuI12. Moreover, BA10EuI12 shows a short excited-state lifetime (151 ns) due to the parity-allowed d-f transition, which boosts the potential of BA10EuI12 for use in real-time dynamic imaging and computer tomography applications. In addition, BA10EuI12 demonstrates a decent linear scintillation response ranging from 9.21 µGyair s-1 to 145 µGyair s-1 and a detection limit as low as 5.83 nGyair s-1. The x-ray imaging measurement was performed using BA10EuI12 polystyrene (PS) composite film as a scintillation screen, which exhibited clear images of objects under x-ray irradiation. The spatial resolution was determined to be 8.95 lp mm-1 at modulation transfer function = 0.2 for BA10EuI12/PS composite scintillation screen. We anticipate that this work will stimulate the exploration of d-f transition lanthanide metal halides for sensitive x-ray scintillators.

Mechanochemical Synthesis of High-Entropy Perovskite toward Highly Sensitive and Stable X-ray Flat-Panel Detectors.

Perovskites are attracting attention for optoelectronic devices. Despite their promise, the large-scale synthesis of perovskite materials with exact stoichiometry, especially high-entropy perovskites, has been a major challenge. Moreover, the difficulty in stoichiometry control also hinders the development of perovskite X-ray flat-panel detectors. Previous reports all employed simple MAPbI3 as the active layer, while the performance still falls short of optimized single-crystal-based single-pixel detectors. Herein, a scalable and universal strategy of a mechanochemical method is adopted to synthesize stoichiometric high-entropy perovskite powders with high quality and high quantity (>1 kg per batch). By utilizing these stoichiometric perovskites, the first FA0.9 MA0.05 Cs0.05 Pb(I0.9 Br0.1 )3 -based X-ray flat-panel detector with low trap density and large mobility-lifetime product (7.5 × 10-3 cm2 V-1 ) is reported. The assembled panel detector exhibits close-to-single-crystal performance (high sensitivity of 2.1 × 104 µC Gyair -1 cm-2 and ultralow detection limit of 1.25 nGyair s-1 ), high spatial resolution of 0.46 lp/pixel, as well as excellent thermal robustness under industrial standards. The high performance in the high-entropy perovskite-based X-ray FPDs has the potential to facilitate the development of new-generation X-ray-detection systems.

Ectopic expression of SARS-CoV-2 S and ORF-9B proteins alters metabolic profiles and impairs contractile function in cardiomyocytes.

Coronavirus disease 2019 (COVID-19) is associated with adverse impacts in the cardiovascular system, but the mechanisms driving this response remain unclear. In this study, we conducted "pseudoviral infection" of SARS-CoV-2 subunits to evaluate their toxic effects in cardiomyocytes (CMs), that were derived from human induced pluripotent stem cells (hiPSCs). We found that the ectopic expression of S and ORF-9B subunits significantly impaired the contractile function and altered the metabolic profiles in human cardiomyocytes. Further mechanistic study has shown that the mitochondrial oxidative phosphorylation (OXPHOS), membrane potential, and ATP production were significantly decreased two days after the overexpression of S and ORF-9B subunits, while S subunits induced higher level of reactive oxygen species (ROS). Two weeks after overexpression, glycolysis was elevated in the ORF-9B group. Based on the transcriptomic analysis, both S and ORF-9B subunits dysregulated signaling pathways associated with metabolism and cardiomyopathy, including upregulated genes involved in HIF-signaling and downregulated genes involved in cholesterol biosynthetic processes. The ORF-9B subunit also enhanced glycolysis in the CMs. Our results collectively provide an insight into the molecular mechanisms underlying SARS-CoV-2 subunits-induced metabolic alterations and cardiac dysfunctions in the hearts of COVID-19 patients.

Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma.

Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. Chelerythrine (CHE), a natural benzophenanthridine alkaloid, has been reported to exhibit the anti-tumor effects in a variety of cancer cells. However, the molecular target and the signaling process of CHE in glioma remain elusive. Here we investigated the underlying mechanisms of CHE in glioma cell lines and glioma xenograft mice model. Our results found that CHE-induced cell death is associated with RIP1/RIP3-dependent necroptosis rather than apoptotic cell death in glioma cells at the early time. Mechanism investigation revealed the cross-talking between necroptosis and mitochondria dysfunction that CHE triggered generation of mitochondrial ROS, mitochondrial depolarization, reduction of ATP level and mitochondrial fragmentation, which was the important trigger for RIP1-dependent necroptosis activation. Meanwhile, PINK1 and parkin-dependent mitophagy promoted clearance of impaired mitochondria in CHE-incubated glioma cells, and inhibition of mitophagy with CQ selectively enhanced CHE-induced necroptosis. Furthermore, early cytosolic calcium from the influx of extracellular Ca2+ induced by CHE acted as important "priming signals" for impairment of mitochondrial dysfunction and necroptosis. Suppression of mitochondrial ROS contributed to interrupting positive feedback between mitochondrial damage and RIPK1/RIPK3 necrosome. Lastly, subcutaneous tumor growth in U87 xenograft was suppressed by CHE without significant body weight loss and multi-organ toxicities. In summary, the present study helped to elucidate necroptosis was induced by CHE via mtROS-mediated formation of the RIP1-RIP3-Drp1 complex that promoted Drp1 mitochondrial translocation to enhance necroptosis. Our findings indicated that CHE could potentially be further developed as a novel therapeutic strategy for treatment of glioma.

Progress on the Effects of Microplastics on Aquatic Crustaceans: A Review.

It is impossible to overlook the effects of microplastics on aquatic life as they continuously accumulate in aquatic environments. Aquatic crustaceans, as both predator and prey, play an important role in the food web and energy transmission. It is of great practical significance to pay attention to the toxic effects of microplastics on aquatic crustaceans. This review finds that most studies have shown that microplastics negatively affect the life history, behaviors and physiological functions of aquatic crustaceans under experimental conditions. The effects of microplastics of different sizes, shapes or types on aquatic crustaceans are different. Generally, smaller microplastics have more negative effects on aquatic crustaceans. Irregular microplastics have more negative effects on aquatic crustaceans than regular microplastics. When microplastics co-exist with other contaminants, they have a greater negative impact on aquatic crustaceans than single contaminants. This review contributes to rapidly understanding the effects of microplastics on aquatic crustaceans, providing a basic framework for the ecological threat of microplastics to aquatic crustaceans.

A review of microplastic pollution in aquaculture: Sources, effects, removal strategies and prospects.

As microplastic pollution has become an emerging environmental issue of global concern, microplastics in aquaculture have become a research hotspot. For environmental safety, economic efficiency and food safety considerations, a comprehensive understanding of microplastic pollution in aquaculture is necessary. This review outlines an overview of sources and effects of microplastics in aquaculture. External environmental inputs and aquaculture processes are sources of microplastics in aquaculture. Microplastics may release harmful additives and adsorb pollutants in aquaculture environment, cause deterioration of aquaculture environment, as well as cause toxicological effects, affect the behavior, growth and reproduction of aquaculture products, ultimately reducing the economic benefits of aquaculture. Microplastics entering the human body through aquaculture products also pose potential health risks at multiple levels. Microplastic pollution removal strategies used in aquaculture in various countries are also reviewed. Ecological interception and purification are considered to be effective methods. In addition, strengthening aquaculture management and improving fishing gear and packaging are also currently feasible solutions. As proactive measures, new portable microplastic monitoring system and remote sensing technology are considered to have broad application prospects. And it was encouraged to comprehensively strengthen the supervision of microplastic pollution in aquaculture through talent exchange and strengthening the construction of laws and regulations.

Contractility and Calcium Transient Maturation in the Human iPSC-Derived Cardiac Microfibers.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are considered immature in the sarcomere organization, contractile machinery, calcium transient, and transcriptome profile, which prevent them from further applications in modeling and studying cardiac development and disease. To improve the maturity of hiPSC-CMs, here, we engineered the hiPSC-CMs into cardiac microfibers (iCMFs) by a stencil-based micropatterning method, which enables the hiPSC-CMs to be aligned in an end-to-end connection for prolonged culture on the hydrogel of physiological stiffness. A series of characterization approaches were performed to evaluate the maturation in iCMFs on both structural and functional levels, including immunohistochemistry, calcium transient, reverse-transcription quantitative PCR, cardiac contractility, and electrical pacing analysis. Our results demonstrate an improved cardiac maturation of hiPSC-CMs in iCMFs compared to micropatterned or random single hiPSC-CMs and hiPSC-CMs in a random cluster at the same cell number of iCMFs. We found an increased sarcomere length, better regularity and alignment of sarcomeres, enhanced contractility, matured calcium transient, and T-tubule formation and improved adherens junction and gap junction formation. The hiPSC-CMs in iCMFs showed a robust calcium cycling in response to the programmed and continuous electrical pacing from 0.5 to 7 Hz. Moreover, we generated the iCMFs with hiPSC-CMs with mutations in myosin-binding protein C (MYBPC3) to have a proof-of-concept of iCMFs in modeling cardiac hypertrophic phenotype. These findings suggest that the multipatterned iCMF connection of hiPSC-CMs boosts the cardiac maturation structurally and functionally, which will reveal the full potential of the application of hiPSC-CM models in disease modeling of cardiomyopathy and cardiac regenerative medicine.

Vertical matrix perovskite X-ray detector for effective multi-energy discrimination.

Multi-energy X-ray detection is sought after for a wide range of applications including medical imaging, security checking and industrial flaw inspection. Perovskite X-ray detectors are superior in terms of high sensitivity and low detection limit, which lays a foundation for multi-energy discrimination. However, the extended capability of the perovskite detector for multi-energy X-ray detection is challenging and has never been reported. Herein we report the design of vertical matrix perovskite X-ray detectors for multi-energy detection, based on the attenuation behavior of X-ray within the detector and machine learning algorithm. This platform is independent of the complex X-ray source components that constrain the energy discrimination capability. We show that the incident X-ray spectra could be accurately reconstructed from the conversion matrix and measured photocurrent response. Moreover, the detector could produce a set of images containing the density-graded information under single exposure, and locate the concealed position for all low-, medium- and high-density substances. Our findings suggest a new generation of X-ray detectors with features of multi-energy discrimination, density differentiation, and contrast-enhanced imaging.