Ultrahigh-Pressure Magnesium Hydrosilicates as Reservoirs of Water in Early Earth.

The origin of water on the Earth is a long-standing mystery, requiring a comprehensive search for hydrous compounds, stable at conditions of the deep Earth and made of Earth-abundant elements. Previous studies usually focused on the current range of pressure-temperature conditions in the Earth's mantle and ignored a possible difference in the past, such as the stage of the core-mantle separation. Here, using ab initio evolutionary structure prediction, we find that only two magnesium hydrosilicate phases are stable at megabar pressures, α-Mg_{2}SiO_{5}H_{2} and ß-Mg_{2}SiO_{5}H_{2}, stable at 262-338 GPa and >338 GPa, respectively (all these pressures now lie within the Earth's iron core). Both are superionic conductors with quasi-one-dimensional proton diffusion at relevant conditions. In the first 30 million years of Earth's history, before the Earth's core was formed, these must have existed in the Earth, hosting much of Earth's water. As dense iron alloys segregated to form the Earth's core, Mg_{2}SiO_{5}H_{2} phases decomposed and released water. Thus, now-extinct Mg_{2}SiO_{5}H_{2} phases have likely contributed in a major way to the evolution of our planet.

Analysis of Raman Spectra by Using Deep Learning Methods in the Identification of Marine Pathogens.

The need for efficient and accurate identification of pathogens in seafood and the environment has become increasingly urgent, given the current global pandemic. Traditional methods are not only time consuming but also lead to sample wastage. Here, we have proposed two new methods that involve Raman spectroscopy combined with a long short-term memory (LSTM) neural network and compared them with a method using a normal convolutional neural network (CNN). We used eight strains isolated from the marine organism Urechis unicinctus, including four kinds of pathogens. After the models were configured and trained, the LSTM methods that we proposed achieved average isolation-level accuracies exceeding 94%, not only meeting the requirement for identification but also indicating that the proposed methods were faster and more accurate than the normal CNN models. Finally, through a computational approach, we designed a loss function to explore the mechanism reflected by the Raman data, finding the Raman segments that most likely exhibited the characteristics of nucleic acids. These novel experimental results provide insights for developing additional deep learning methods to accurately analyze complex Raman data.

Combination of an Artificial Intelligence Approach and Laser Tweezers Raman Spectroscopy for Microbial Identification.

Raman spectroscopy is a nondestructive, label-free, highly specific approach that provides the chemical information on materials. Thus, it is suitable to be used as an effective analytical tool to characterize biological samples. Here we introduce a novel method that uses artificial intelligence to analyze biological Raman spectra and identify the microbes at a single-cell level. The combination of a framework of convolutional neural network (ConvNet) and Raman spectroscopy allows the extraction of the Raman spectral features of a single microbial cell and then categorizes cells according to their spectral features. As the proof of concept, we measured Raman spectra of 14 microbial species at a single-cell level and constructed an optimal ConvNet model using the Raman data. The average accuracy of classification by ConvNet is 95.64 ± 5.46%. Meanwhile, we introduced an occlusion-based Raman spectra feature extraction to visualize the weights of Raman features for distinguishing different species.

Treatment and nursing care of a patient diagnosed with malignant hyperthermia after general anesthesia: a case report.

Malignant hyperthermia (MH), characterized by severe myoclonus, pyrexia, tachycardia, hypertension, elevated muscle enzymes, and hypercapnia, often occurs in patients with congenital deformities or genetic disorders. Although the reported incidence rate is as low as 1:5000 to 1:100,000, patients with MH exhibit rapid aggravation and an elevated mortality rate. Thus, MH is associated with substantial perioperative risk. Successful treatment of patients with MH largely depends on early diagnosis and timely effective treatment. This clinical report provides a detailed description of a patient with newly diagnosed MH who developed a rapid rise in body temperature, end-tidal carbon dioxide, and heart rate during maxillary osteotomy. After successful rescue, the patient recovered smoothly during the postoperative period, indicating the importance of intraoperative monitoring, early diagnosis, effective treatment, and postoperative monitoring. This case is expected to serve as a reference for future interventions and healthcare practices in managing other patients with MH.

Flexible and stretchable implantable devices for peripheral neuromuscular electrophysiology.

The peripheral nervous and muscular system, a cornerstone of human physiology, plays a pivotal role in ensuring the seamless functioning of the human body. This intricate network, comprising nerves and muscles extending throughout the body, is essential for motor control, sensory feedback, and the regulation of autonomic bodily functions. The qualified implantable peripheral interface can accurately monitor the biopotential of the target tissue and conduct treatment with stimulation, enhancing the human-machine interaction and new achievements in disease cure. Implantable electrodes have revolutionized the field of neuromuscular interfaces, offering precise bidirectional communication between the neuromuscular system and external devices. They enable natural control for individuals with limb loss, bridging the gap between mind and machine and aiding neuromuscular rehabilitation. In research and medical diagnostics, implantable electrodes provide invaluable tools for studying neuromuscular function and the development of therapies. However, traditional rigid electrodes face challenges due to the dynamic nature of the peripheral neuromuscular system. Flexible and stretchable devices show immense promise in accommodating dynamic alterations, offering adaptability, and accurate monitoring of electrophysiological signals. This review delves into the challenges associated with the peripheral interface, primarily focusing on monitoring and stimulation. It then provides a summary of common materials and structural design optimizations, discusses technologies for enhancing interface adhesion and surface functionalization, and explores encapsulation methods for implanted devices. Recent advancements in energy supply and the applications of implantable, flexible, and stretchable devices are also comprehensively reviewed, with due consideration given to ethical concerns and signal analysis. The promising directions are finally presented to provide enlightenment for high-performance sensor-tissue interfaces in the future, which will promote profound progress in clinical and human-machine interaction research. Flexible and stretchable devices are at the forefront of healthcare, with the potential to transform the treatment of neuromuscular disorders and enhance human augmentation, blurring the lines between natural and artificial limbs. They represent a promising avenue for the future, with exciting applications in healthcare, science, and technology, promising to bring us closer to the seamless integration of human and machine in the realm of neuromuscular interfaces.

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting purine metabolism and polyamine synthesis-associated vascular remodeling.

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.

Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.

A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Living Synthelectronics: A New Era for Bioelectronics Powered by Synthetic Biology.

Bioelectronics, which converges biology and electronics, has attracted great attention due to their vital applications in human-machine interfaces. While traditional bioelectronic devices utilize nonliving organic and/or inorganic materials to achieve flexibility and stretchability, a biological mismatch is often encountered because human tissues are characterized not only by softness and stretchability but also by biodynamic and adaptive properties. Recently, a notable paradigm shift has emerged in bioelectronics, where living cells, and even viruses, modified via gene editing within synthetic biology, are used as core components in a new hybrid electronics paradigm. These devices are defined as "living synthelectronics," and they offer enhanced potential for interfacing with human tissues at informational and substance exchange levels. In this Perspective, the recent advances in living synthelectronics are summarized. First, opportunities brought to electronics by synthetic biology are briefly introduced. Then, strategic approaches to designing and making electronic devices using living cells/viruses as the building blocks, sensing components, or power sources are reviewed. Finally, the challenges faced by living synthelectronics are raised. It is believed that this paradigm shift will significantly contribute to the real integration of bioelectronics with human tissues.

Identification of Zip8-correlated hub genes in pulmonary hypertension by informatic analysis.

Background: Pulmonary hypertension (PH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and increased pulmonary vascular resistance, ultimately leading to right heart failure and even death. The localization of Zrt/Irt-like Protein 8 (ZIP8, a metal ion transporter, encoded by SLC39A8) was abundantly in microvasculature endothelium and its pivotal role in the lung has been demonstrated. However, the role of Zip8 in PH remains unclear. Methods: Bioinformatics analysis was employed to identify SLC39A8 expression patterns and differentially expressed genes (DEGs) between PH patients and normal controls (NC), based on four datasets (GSE24988, GSE113439, GSE117261, and GSE15197) from the Biotechnology Gene Expression Omnibus (NCBI GEO) database. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways enriched for DEGs. Hub genes were identified by cytoHubba analysis in Cytoscape. Reverse transcriptase-polymerase chain reaction was used to validate SLC39A8 and its correlated metabolic DEGs expression in PH (SU5416/Hypoxia) mice. Results: SLC39A8 expression was downregulated in PH patients, and this expression pattern was validated in PH (SU5416/Hypoxia) mouse lung tissue. SLC39A8-correlated genes were mainly enriched in the metabolic pathways. Within these SLC39A8-correlated genes, 202 SLC39A8-correlated metabolic genes were screened out, and seven genes were identified as SLC39A8-correlated metabolic hub genes. The expression patterns of hub genes were analyzed between PH patients and controls and further validated in PH mice. Finally, four genes (Fasn, Nsdhl, Acat2, and Acly) were downregulated in PH mice. However, there were no significant differences in the expression of the other three hub genes between PH mice and controls. Of the four genes, Fasn and Acly are key enzymes in fatty acids synthesis, Nsdhl is involved in cholesterol synthesis, and Acat2 is implicated in cholesterol metabolic transformation. Taken together, these results provide novel insight into the role of Zip8 in PH.

Progressively Oriented Attachment-Enabled Ultralong Single-Crystalline Upconversion Nanowires for Multidirectional Strain Sensing.

Fabricating one-dimensional (1D) single-crystalline nanostructures with the necessary characteristics for interconnects and functional units in nanodevices poses a major challenge. Traditional solution-based synthesis methods, driven by oriented attachment mechanisms, have limited the growth of either ultrathin crystalline nanowires or short rod-like nanocrystals due to stringent orientation requirements. The construction of single-crystalline ultralong nanowires with both an elongated length and moderate thickness has remained elusive. Here we introduce a growth mechanism based on progressively oriented attachment that enables the attachment of larger crystals while preserving the alignment of the crystal lattice. Using this mechanism, we achieve 1D single-crystalline lanthanide-doped nanowires (K2YF5:Yb/Er) with lengths up to 9 µm and a moderate thickness of approximately 20 nm. These nanowires can be integrated into a flexible film that exhibits stretching-dependent upconverted luminescence behavior. The mechanical toughness and elongated morphology of the nanowires facilitate the development of a wearable device dedicated to multidirectional strain sensing with high responsivity and excellent stability, withstanding repeated stretching and releasing for up to 1000 cycles.

A ring N(CH3)2-based derivative of resveratrol inhibits pulmonary vascular remodeling in hypoxia pulmonary hypertension.

Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH3)2-based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O2). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O2). Res4 (10 µM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR.

Erratum: A crack compensation strategy for highly stretchable conductors based on liquid metal inclusions.

[This corrects the article DOI: 10.1016/j.isci.2022.105495.].

Regulatory of miRNAs in tri-lineage differentiation of C3H10T1/2.

MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which play a vital role in cell generation, metabolism, apoptosis and stem cell differentiation. C3H10T1/2, a mesenchymal cell extracted from mouse embryos, is capable of osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation. Extensive studies have shown that not only miRNAs can directly trigger targeted genes to regulate the tri-lineage differentiation of C3H10T1/2, but it also can indirectly regulate the differentiation by triggering different signaling pathways or various downstream molecules. This paper aims to clarify the regulatory roles of different miRNAs on C3H10T1/2 differentiation, and discussing their balance effect among osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation of C3H10T1/2. We also review the biogenesis of miRNAs, Wnt signaling pathways, MAPK signaling pathways and BMP signaling pathways and provide some specific examples of how these signaling pathways act on C3H10T1/2 tri-lineage differentiation. On this basis, we hope that a deeper understanding of the differentiation and regulation mechanism of miRNAs in C3H10T1/2 can provide a promising therapeutic method for the clinical treatment of bone defects, osteoporosis, osteoarthritis and other diseases.

Recent advances in flexible and wearable sensors for monitoring chemical molecules.

In recent years, real-time health management has received increasing attention, benefiting from the rapid development of flexible and wearable devices. Conventionally, flexible and wearable devices are used for collecting health data such as electrophysiological signals, blood pressure, heart rate, etc. The monitoring of chemical factors has shown growing significance, providing the basis for the screening, diagnosis, and treatment of many diseases. Nowadays, in order to understand the health status of the human body more comprehensively and accurately, researchers in the community have started putting effort into developing wearable devices for monitoring chemical factors. Progressively, more flexible chemical sensors with wearable real-time health-monitoring functionality have been developed thanks to advances relating to wireless communications and flexible electronics. In this review, we describe the variety of chemical molecules and information that can currently be monitored, including pH levels, glucose, lactate, uric acid, ion levels, cytokines, nutrients, and other biomarkers. This review analyzes the pros and cons of the most advanced wearable chemical sensors in terms of wearability. At the end of this review, we discuss the current challenges and development trends relating to flexible and wearable chemical sensors from the aspects of materials, electrode designs, and soft-hard interface connections.

A crack compensation strategy for highly stretchable conductors based on liquid metal inclusions.

Crack control strategies have been proven very useful for enhancing the stretchability of metal film-based stretchable conductors. However, existing strategies often suffer from the drawbacks of complicated preparation and predefined effective directions. Here, we propose a crack compensation strategy for preparing conductors featured with high stretchability by using liquid metal microparticles (LMMPs)-embedded polydimethylsiloxane (PDMS) as the substrate with a thin film of gold (Au) sputtered on the surface. LMMPs can be elongated to connect the cracked Au film upon stretching, which can form a conductive "island-tunnel" (IT) architecture to compensate for the cracks and maintain the conductivity. The high performance of the stretchable conductor is demonstrated by using it as electrodes to record surface electromyography of human brachioradialis and monitor electrocorticography signals of a rat in normal and epileptic states. The developed strategy shows the potential to provide a new perspective for the fabrication of flexible electronics.

Effects of Cognitive Load on the Categorical Perception of Mandarin Tones.

Purpose This study investigated the effect of cognitive load (CL) on the categorical perception (CP) of Mandarin lexical tones to discuss the application of the generalized pulse-skipping hypothesis. This hypothesis assumes that listeners might miss/skip temporal pulses and lose essential speech information due to CL, which consequently affects both the temporal and spectral dimensions of speech perception. Should CL decrease listeners' pitch sensitivity and impair the distinction of tone categories, this study would support the generalized pulse-skipping hypothesis. Method Twenty-four native Mandarin-speaking listeners were recruited to complete a dual-task experiment where they were required to identify or discriminate tone stimuli while concurrently memorizing six Chinese characters or graphic symbols. A no-load condition without a memory recall task was also included as a baseline condition. The position of categorical boundary, identification slope, between- and within-category discrimination, and discrimination peakedness were compared across the three conditions to measure the impact of CL on tone perception. The recall accuracy of Chinese characters and graphic symbols was used to assess the difficulty of memory recall. Results Compared with the no-load condition, both load conditions showed a boundary shift to Tone 3, shallower identification slope, poorer between-category discrimination, and lower discrimination peakedness. Within-category discrimination was negatively affected by CL in the graphic symbol condition only, not in the Chinese character condition. Conclusions CL degraded listeners' sensitivity to subtle fundamental frequency changes and impaired CP of Mandarin lexical tones. This provides support for the generalized pulse-skipping hypothesis. Besides, the involvement of lexical information modulated the effect of CL.

Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced enteropathy.

In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate the unexplored role of CRAMP in celiac disease. By applying a mouse model of gluten-induced enteropathy (GIE) recapitulating small intestinal enteropathy of celiac disease, we observed defective CRAMP production in duodenal epithelium during GIE. CRAMP-deficient mice were susceptible to the development of GIE. Exogenous CRAMP corrected gliadin-triggered epithelial dysfunction and promoted regulatory immune responses at the intestinal mucosa. Additionally, GIE-associated gut dysbiosis with enriched Pseudomonas aeruginosa and production of the protease LasB contributed to defective intestinal CRAMP production. These results highlight microbiota-CRAMP axis in the modulation of barrier function and immune responses in GIE. Hence, modulating CRAMP may represent a therapeutic strategy for celiac disease.

Classification of pathogens by Raman spectroscopy combined with generative adversarial networks.

Rapid identification of marine pathogens is very important in marine ecology. Artificial intelligence combined with Raman spectroscopy is a promising choice for identifying marine pathogens due to its rapidity and efficiency. However, considering the cost of sample collection and the challenging nature of the experimental environment, only limited spectra are typically available to build a classification model, which hinders qualitative analysis. In this paper, we propose a novel method to classify marine pathogens by means of Raman spectroscopy combined with generative adversarial networks (GANs). Three marine strains, namely, Staphylococcus hominis, Vibrio alginolyticus, and Bacillus licheniformis, were cultured. Using Raman spectroscopy, we acquired 100 spectra of each strain, and we fitted them into GAN models for training. After 30,000 training iterations, the spectra generated by G were similar to the actual spectra, and D was used to test the accuracy of the spectra. Our results demonstrate that our method not only improves the accuracy of machine learning classification but also solves the problem of requiring a large amount of training data. Moreover, we have attempted to find potential identifying regions in the Raman spectra that can be used for reference in subsequent related work in this field. Therefore, this method has tremendous potential to be developed as a tool for pathogen identification.

Fine-tuning the expression of target genes using a DDI2 promoter gene switch in budding yeast.

Tuned gene expression is crucial to the proper growth and response to the environmental changes of an organism. To enable tunable gene expression as designed is desirable in both scientific research and industrial application. Here, we introduce a novel promoter switching method based on the DDI2 promoter (PDDI2) that can fine tune the expression of target genes. We constructed a recyclable cassette (PDDI2-URA3-PDDI2) and integrated it upstream of yeast target genes to replace the native promoters by DDI2 promoter without introducing any junk sequence. We found that the presence or absence of cyanamide as an inducer could turn on or off the expression of target genes. In addition, we showed that PDDI2 could act as a gene switch to linearly regulate the expression levels of target genes in vivo. We switched the original promoters of RAD18, TUP1, and CDC6 with PDDI2 as a proof-of-concept.