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Summary: X-ray detection is crucial across various sectors, but traditional techniques face challenges such as inefficient data transmission, redundant sensing, high power consumption, and complexity. The innovative idea of a retinomorphic X-ray detector shows great potential. However, its implementation has been hindered by the absence of active layers capable of both detecting X-rays and serving as memory storage. In response to this critical gap, our study integrates hybrid perovskite with hydrion-conductive organic cations to develop a groundbreaking retinomorphic X-ray detector. This novel device stands at the nexus of technological innovation, utilizing X-ray detection, memory, and preprocessing capabilities within a single hardware platform. The core mechanism underlying this innovation lies in the transport of electrons and holes within the metal halide octahedral frameworks, enabling precise X-ray detection. Concurrently, the hydrion movement through organic cations endows the device with short-term resistive memory, facilitating rapid data processing and retrieval. Notably, our retinomorphic X-ray detector boasts an array of formidable features, including reconfigurable short-term memory, a linear response curve, and an extended retention time. In practical terms, this translates into the efficient capture of motion projections with minimal redundant data, achieving a compression ratio of 18.06% and an impressive recognition accuracy of up to 98.6%. In essence, our prototype represents a paradigm shift in X-ray detection technology. With its transformative capabilities, this retinomorphic hardware is poised to revolutionize the existing X-ray detection landscape.

Abstract 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.

Respiratory-induced tumor motion presents a critical challenge in lung cancer radiotherapy, potentially impacting treatment precision and efficacy. This study introduces an innovative, deep learning-based approach for real-time, markerless lung tumor tracking utilizing orthogonal X-ray projection images. It incorporates three key components: (1) a sophisticated data augmentation technique combining a hybrid deformable model with 3D thin-plate spline transformation, (2) a state-of-the-art Transformer-based segmentation network for precise tumor boundary delineation, and (3) a CNN regression network for accurate 3D tumor position estimation. We rigorously evaluated this approach using both patient data from The Cancer Imaging Archive and dynamic thorax phantom data, assessing performance across various noise levels and comparing it with current leading algorithms. For TCIA patient data, the average DSC and HD95 values were 0.9789 and 1.8423 mm, respectively, with an average centroid localization deviation of 0.5441 mm. On CIRS phantoms, DSCs were 0.9671 (large tumor) and 0.9438 (small tumor) with corresponding HD95 values of 1.8178 mm and 1.9679 mm. The 3D centroid localization accuracy was consistently below 0.33 mm. The processing time averaged 90 ms/frame. Even under high noise conditions (S2 = 25), errors for all data remained within 1 mm with tracking success rates mostly at 100%. In conclusion, the proposed markerless tracking method demonstrates superior accuracy, noise robustness, and real-time performance for lung tumor localization during radiotherapy. Its potential to enhance treatment precision, especially for small tumors, represents a significant step toward improving radiotherapy efficacy and personalizing cancer treatment.

Abstract 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.

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.

Abstract 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.

Summary: 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.

Abstract Metal halide perovskites (MHPs) have demonstrated excellent performances in detection of X-rays and gamma-rays. Most studies focus on improving the sensitivity of single-pixel MHP detectors. However, little work pays attention to the dark current, which is crucial for the back-end circuit integration. Herein, the requirement of dark current is quantitatively evaluated as low as 10−9 A/cm2 for X-ray imagers integrated on pixel circuits. Moreover, through the semiconductor device analysis and simulation, we reveal that the main current compositions of thick perovskite X-ray detectors are the thermionic-emission current (J T) and the generation-recombination current (J g-r). The typical observed failures of p–n junctions in thick detectors are caused by the high generation-recombination current due to the band mismatch and interface defects. This work provides a deep insight into the design of high sensitivity and low dark current perovskite X-ray detectors. Graphical Abstract

The vertical matrix perovskite X-ray detectors for multi-energy detection is reported, providing a new generation of X-ray detectors with features of multi-energy discrimination, density differentiation and contrast-enhanced.

A human cardiac organoid system, coupled with single cell RNA sequencing and machine learning for transcriptional phenotyping, was developed. This allowed investigation of a genetic variant associated with Ebstein’s Anomaly, a congenital heart disease with chamber defects.

Abstract A ratiometric genetically encoded voltage indicator (GEVI) would be desirable for tracking transmembrane voltage changes in the presence of sample motion. We performed combinatorial multi-site mutagenesis on a cyan-excitable red fluorescent protein to create the bright and monomeric mCyRFP3, which proved to be uniquely non-perturbing when fused to the GEVI ASAP3. The green/red ratio from ASAP3-mCyRFP3 (ASAP3-R3) reported voltage while correcting for motion artifacts, allowing the visualization of membrane voltage changes in contracting cardiomyocytes and throughout the cell cycle of motile cells.

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.

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.

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.

Abstract Sensitive and fast detection of neutrons and gamma rays is vital for homeland security, high‐energy physics, and proton therapy. Fast‐neutron detectors rely on light organic scintillators, and γ‐ray detectors use heavy inorganic scintillators and semiconductors. Efficient mixed‐field detection using a single material is highly challenging due to their contradictory requirements. Here we report hybrid perovskites (C8H12N)2Pb(Br1−xClx)4 that combine light organic cations and heavy inorganic skeletons at a molecular level to achieve unprecedented performance for mixed‐field radiation detection. High neutron absorption due to a high density of hydrogen, strong radiative recombination within the highly confined [PbX6]4− layer, and sub‐nanometer distance between absorption sites and radiative centers, enable a light yield of 41 000 photons/MeV, detection pulse width of 2.97 ns and extraordinary linearity response toward both fast neutrons and γ‐rays, outperforming commonly used fast‐neutron scintillators. Neutron energy spectrum, time‐of‐flight based fast‐neutron/γ‐ray discrimination and neutron yield monitoring were all successfully achieved using (C8H12N)2Pb(Br0.95Cl0.05)4 detectors. We further demonstrate the monitoring of reaction kinetics and total power of a nuclear fusion reaction. We envision that molecular hybridized scintillators open a new avenue for mixed‐field radiation detection and imaging.

Abstract Generating cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) has represented a significant advance in our ability to model cardiac disease. Current differentiation protocols, however, have limited use due to their production of heterogenous cell populations, primarily consisting of ventricular-like CMs. Here we describe the creation of two chamber-specific reporter hiPSC lines by site-directed genomic integration using CRISPR-Cas9 technology. In the MYL2-tdTomato reporter, the red fluorescent tdTomato was inserted upstream of the 3′ untranslated region of the Myosin Light Chain 2 (MYL2) gene in order faithfully label hiPSC-derived ventricular-like CMs while avoiding disruption of endogenous gene expression. Similarly, in the SLN-CFP reporter, Cyan Fluorescent Protein (CFP) was integrated downstream of the coding region of the atrial-specific gene, Sarcolipin (SLN). Purification of tdTomato+ and CFP+ CMs using flow cytometry coupled with transcriptional and functional characterization validated these genetic tools for their use in the isolation of bona fide ventricular-like and atrial-like CMs, respectively. Finally, we successfully generated a double reporter system allowing for the isolation of both ventricular and atrial CM subtypes within a single hiPSC line. These tools provide a platform for chamber-specific hiPSC-derived CM purification and analysis in the context of atrial- or ventricular-specific disease and therapeutic opportunities.

Citrus Huanglongbing (HLB) is the most devastating disease of citrus caused by the Gram-negative phloem-limited bacterium “Candidatus Liberibacter asiaticus” (CLas). It can be transmitted by the Asian citrus psyllid “Diaphorina citri,” by grafting, and by the holoparasitic dodder. In this study, the non-natural host periwinkle (Catharanthus roseus) was infected via dodder (Cuscuta campestris) from CLas-infected citrus plants, and the asymptomatic leaves (AS) were subjected to transcriptomic and small-RNA profiling. The results were analyzed together with a transcriptome dataset from the NCBI repository that included leaves for which symptoms had just occurred (S) and yellowing leaves (Y). There were 3,675 differentially expressed genes (DEGs) identified in AS, and 6,390 more DEGs in S and further 2109 DEGs in Y. These DEGs were commonly enriched in photosystem, chloroplast, membrane, oxidation-reduction process, metal/zinc ion binding on GO. A total of 14,974 DEGs and 336 DE miRNAs (30 conserved and 301 novel) were identified. Through weighted gene co-expression network and nested network analyses, two critical nested miRNA–mRNA regulatory networks were identified with four conserved miRNAs. The primary miR164-NAC1 network is potentially involved in plant defense responses against CLas from the early infection stage to symptom development. The secondary network revealed the regulation of secondary metabolism and nutrient homeostasis through miR828-MYB94/miR1134-HSF4 and miR827-ATG8 regulatory networks, respectively. The findings discovered new potential mechanisms in periwinkle–CLas interactions, and its confirmation can be done in citrus–CLas system later on. The advantages of periwinkle plants in facilitating the quick establishment and greater multiplication of CLas, and shortening latency for disease symptom development make it a great surrogate for further studies, which could expedite our understanding of CLas pathogenesis.

As the most common cause of heart failure, dilated cardiomyopathy (DCM) is characterized by dilated ventricles and weakened contractile force. Mutations in the calcium handling protein phospholamban (PLN) are known to cause inherited DCM. Here, we introduced a PLN-R9C mutation in a healthy control induced pluripotent stem cell (iPSC) line using CRISPR/Cas9. The genome-edited iPSC line showed typical pluripotent cell morphology, robust expression of pluripotency markers, normal karyotype, and the capacity to differentiate into all three germ layers in vitro. The PLN-R9C iPSC line provides a valuable resource to dissect the molecular mechanisms underlying PLN mutation-related DCM.

Summary: With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function. : In this article, Wu and colleagues demonstrate that human cardiomyocytes, like the whole heart, change their contractile properties in microgravity and compensate for the apparent loss of gravity by altering their gene-expression patterns. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function at the cellular level. Keywords: cardiomyocytes, cardiology, induced pluripotent stem cells, microgravity, spaceflight, heart, stem cell, calcium imaging, modeling, metabolism

Abstract Background Hfq is a widely conserved bacterial RNA-binding protein which generally mediates the global regulatory activities involv ed in physiological process and virulence. The goal of this study was to characterize the biological function of hfq gene in Xanthomonas axonpodis pv. citri (Xac), the causal agent of citrus canker disease. Results An hfq mutant in Xac was generated by plasmid integration. The loss of hfq resulted in attenuation of bacterial growth, motility and biofilm formation. In addition, the hfq mutation impaired Xac resistance to H2O2 and both high and low pH environments, but did not affect the virulence to citrus. RNA-Seq analyses indicated that Hfq played roles in regulating the expression of 746 genes. In hfq mutant, gene expression related to chemotaxis, secretion system, two-component system, quorum sensing and flagellar assembly were repressed, whereas expression of ribosomal genes were significantly up-regulated. The down-regulated expression of three bacterial chemotaxis related genes and seven flagella genes, which involved in cell growth and biofilm formation, were further validated by RT-qPCR. Conclusions The study demonstrated that hfq was involved in multiple biological processes in Xac. The results could serve as initiate points for identifying regulatory sRNAs and genes controlled by Hfq-sRNA interactions in Xac.

Ionic migration degrades not only the characteristics of halide perovskite solar cells, but also those of perovskite X-ray detectors. Here Yang et al. employ heteroepitaxial BiOBr to passivate Cs2AgBiBr6 double perovskite, which suppresses ionic migration and obtain high performance X-ray detectors.

Danon disease (DD) is caused by mutations of the gene encoding lysosomal-associated membrane protein type 2 (LAMP2), which lead to impaired autophagy, glycogen accumulation, and cardiac hypertrophy. However, it is not well understood why a large portion of DD patients develop arrhythmia and sudden cardiac death. In the current study, we generated LAMP2 knockout (KO) human iPSC-derived cardiomyocytes (CM), which mimic the LAMP2 dysfunction in DD heart. Morphologic analysis demonstrated the sarcomere disarrangement in LAMP2 KO CMs. In functional studies, LAMP2 KO CMs showed near-normal calcium handling at base level. However, treatment of pro-maturation medium (MM) exaggerated the disease phenotype in the KO cells as they exhibited impaired calcium recycling and increased irregular beating events, which recapitulates the pro-arrhythmia phenotypes of DD patients. Further mechanistic study confirmed that MM treatment significantly enhanced the autophagic stress in the LAMP2 KO CMs, which was accompanied by an increase of both cellular and mitochondrial reactive oxygen species (ROS) levels. Excess ROS accumulation in LAMP2 KO CMs resulted in the over-activation of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and arrhythmogenesis, which was partially rescued by the treatment of ROS scavenger. In summary, our study has revealed ROS induced CaMKIIδ overactivation as a key mechanism that promotes cardiac arrhythmia in DD patients.

Human induced pluripotent stem cell derived cardiomyocytes are a powerful model for cardiogenesis and disease in vitro. Here the authors comprehensively map cardiac differentiation using multiple modalities, including single-cell RNA seq and CyTOF, in cells with a gain or loss of function in key cardiac transcription factors.

Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity. By imaging ASAP2s using random-access multi-photon microscopy, we demonstrate robust single-trial detection of action potentials in organotypic slice cultures. We also show that ASAP2s enables two-photon imaging of graded potentials in organotypic slice cultures and in Drosophila. These results demonstrate that the combination of ASAP2s and fast two-photon imaging methods enables detection of neural electrical activity with subcellular spatial resolution and millisecond-timescale precision.