Electrode stability can be controlled to a large extent by constructing suitable composite structures, in which the heterojunction structure can affect the transport of electrons and ions through the effect of the interface state, changed band gap width, and the electric field at the interface. As a promising electrode material, the Ga-based material has a conversion between solid and liquid phases in the electrochemical reaction process, which endows it with self-healing properties with the structure and morphology. Based on these, the Ga2O3/MnCO3 composite was successfully synthesized with a heterogeneous structure by introducing a Ga source in the hydrothermal process. Benefitting from the acceleration effect of the internal electric field and the narrower band gap at the interface, a high-capacity Ga2O3/MnCO3 composite electrode (1112 mAh·g-1 after 225 cycles at 0.1 A·g-1 and 457.1 mAh·g-1 after 400 cycles at 1 A·g-1) can be achieved for lithium-ion batteries. The results can provide a reference for the research and preparation of electrode materials with high performance.
Extracellular vesicles are nano- to microscale, membrane-bound particles released by cells into extracellular space, and act as carriers of biomarkers and therapeutics, holding promising potential in translational medicine. However, the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment. Here, we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles. We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies. We discuss the acoustic-assisted diagnostic methods including the purification, manipulation, biosensing, and bioimaging of extracellular vesicles. Then, we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles. Finally, we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.
AIMS: To investigate the prevalence of anxiety and depression symptoms in intensive care unit (ICU) patients with cardiovascular disease (CVD) and to explore which elements are risk factors for the development of anxiety and depression symptoms. DESIGN: A cross-sectional study. METHODS: A total of 1028 ICU patients with CVD were enrolled in this cross-sectional study. Logistic regression was used to assess risk factors and associations between anxiety and depression symptoms, and mediation analysis was used to explore the effect of risk factors on the association between anxiety and depression symptoms. Reporting of the study followed the STROBE checklist. RESULTS: The results showed that among ICU patients with CVD, 38.1% had anxiety symptoms, 28.7% had depression symptoms and 19.3% had both anxiety and depression symptoms, and there was a significant association between anxiety and depression symptoms. We also identified female gender, hypertension, hyperlipidemia and cardiac function class IV as independent risk factors for anxiety and depression symptoms. Importantly, these factors also mediated the association between anxiety and depression symptoms, emphasising their role in the psychological well-being of this patient group. CONCLUSION: ICU patients with CVD were prone to anxiety and depression symptoms. Female gender, hypertension, hyperlipidemia and cardiac function class IV were identified as independent risk factors that also served as mediators in the relationship between anxiety and depression symptoms. Especially, cardiac function class IV emerged as a critical factor in this association. RELEVANCE TO CLINICAL PRACTICE: It is imperative for critical care professionals to recognize the elevated risk of depression and anxiety among ICU patients with severe CVD, especially those with cardiac function class IV, hypertension, hyperlipidemia and females. Proactive and supportive measures are essential for this vulnerable group during their ICU stay to safeguard their mental health and prevent negative outcomes. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
Typically, in the manufacturing of GH4169 superalloy forgings, the multi-process hot forming that consists of pre-deformation, heat treatment and final deformation is required. This study focuses on the microstructural evolution throughout hot working processes. Considering that δ phase can promote nucleation and limit the growth of grains, a process route was designed, including pre-deformation, aging treatment (AT) to precipitate sufficient δ phases, high temperature holding (HTH) to uniformly heat the forging, and final deformation. The results show that the uneven strain distribution after pre-deformation has a significant impact on the subsequent refinement of the grain microstructure due to the complex coupling relationship between the evolution of the δ phase and recrystallization behavior. After the final deformation, the fine-grain microstructure with short rod-like δ phases as boundaries is easy to form in the region with a large strain of the pre-forging. However, necklace-like mixed grain microstructure is formed in the region with a small strain of the pre-forging. In addition, when the microstructure before final deformation consists of mixed grains, dynamic recrystallization (DRX) nucleation behavior preferentially depends on kernel average misorientation (KAM) values. A large KAM can promote the formation of DRX nuclei. When the KAM values are close, a smaller average grain size of mixed-grain microstructure is more conductive to promote the DRX nucleation. Finally, the interaction mechanisms between δ phase and DRX nucleation are revealed.
Alzheimer's disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/µL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aß EVs at different time courses, and compared them with intraneuronal Aß cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer's and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.
Sodium-ion batteries (SIBs) are potential candidates for large energy storage usage because of the natural abundance and cheap sodium. Nevertheless, improving the energy density and cycling steadiness of SIB cathodes remains a challenge. In this work, F-doping Na3 Al2/3 V4/3 (PO4 )3 (NAVP) microspheres (Na3 Al2/3 V4/3 (PO4 )2.9 F0.3 (NAVPF)) are synthesized via spray drying and investigated as SIB cathodes. XRD and Rietveld refinement reveal expanded lattice parameters for NAVPF compared to the undoped sample, and the successful cation doping into the Na superionic conductor (NASICON) framework improves Na+ diffusion channels. The NAVPF delivers an ultrahigh capacity of 148 mAh g-1 at 100 mA g-1 with 90.8% retention after 200 cycles, enabled by the activation of V2+ /V5+ multielectron reaction. Notably, NAVPF delivers an ultrahigh rate performance, with a discharge capacity of 83.6 mAh g-1 at 5000 mA g-1 . In situ XRD demonstrates solid-solution reactions occurred during charge-discharge of NAVPF without two-phase reactions, indicating enhanced structural stability after F-doped. The full cell with NAVPF cathode and Na+ preintercalated hard carbon anode shows a large discharge capacity of 100 mAh g-1 at 100 mA g-1 with 80.2% retention after 100 cycles. This anion doping strategy creates a promising SIB cathode candidate for future high-energy-density energy storage applications.
Nitrogen (N) is an important nutrient for crop growth. However, the overuse of N fertilizers has led to a series of devastating global environmental issues. Recent studies show that multiple datasets have been created for agricultural N fertilizer application with varied temporal or spatial resolutions, nevertheless, how to synchronize and use these datasets becomes problematic due to the inconsistent temporal coverages, spatial resolutions, and crop-specific allocations. Here we reconstructed a comprehensive dataset for crop-specific N fertilization at 5-arc-min resolution (~10 km by 10 km) during 1961-2020, including N application rate, types, and placements. The N fertilization data was segmented by 21 crop groups, 13 fertilizer types, and 2 fertilization placements. Comparison analysis showed that our dataset is aligned with previous estimates. Our spatiotemporal N fertilization dataset could be used for the land surface models to quantify the effects of agricultural N fertilization practices on food security, climate change, and environmental sustainability.
Acute lung injury (ALI) is a common lung disease with increasing morbidity and mortality rates due to the lack of specific drugs. Impaired alveolar fluid clearance (AFC) is a primary pathological feature of ALI. Epithelial sodium channel (ENaC) is a primary determinant in regulating the transport of Na+ and the clearance of alveolar edema fluid. Therefore, ENaC is an important target for the development of drugs for ALI therapy. However, the role of ENaC in the progression of ALI remains unclear. Inhibition of early growth response factor (EGR-1) expression has been reported to induce a protective effect on ALI; therefore, we evaluated whether EGR-1 participates in the progression of ALI by regulating ENaC-α in alveolar epithelium. We investigated the potential mechanism of EGR-1-mediated regulation of ENaC in ALI. We investigated whether EGR-1 aggravates the pulmonary edema response in ALI by regulating ENaC. ALI mouse models were established by intrabronchial injection of lipopolysaccharides (LPS). Lentiviruses with EGR-1 knockdown were transfected into LPS-stimulated A549 cells. We found that EGR-1 expression was upregulated in the lung tissues of ALI mice and in LPS-induced A549 cells, and was negatively correlated with ENaC-α expression. Knockdown of EGR-1 increased ENaC-α expression and relieved cellular edema in ALI. Moreover, EGR-1 regulated ENaC-α expression at the transcriptional level, and correspondingly promoted pulmonary edema and aggravated ALI symptoms. In conclusion, our study demonstrated that EGR-1 could promote pulmonary edema by downregulating ENaC-α at the transcriptional level in ALI. Our study provides a new potential therapeutic strategy for treatment of ALI.
EGR-1 expression was increased in LPS-induced ALI mice and associated with aggravated pulmonary edemaEGR-1 induced pulmonary edema relying on regulating the expression of ENaC-α at the transcriptional level by manipulating the promoter.
Acute Lung Injury , Pulmonary Edema , Animals , Humans , Mice , A549 Cells , Acute Lung Injury/chemically induced , Epithelial Sodium Channels/genetics , Lipopolysaccharides
Manganese hexacyanoferrate (MnHCF) is one of the most promising cathode materials for aqueous battery because of its non-toxicity, high energy density, and low cost. But the phase transition from MnHCF to Zinc hexacyanoferrate (ZnHCF) and the larger Stokes radius of Zn2+ cause rapid capacity decay and poor rate performance in aqueous Zn battery. Hence, to overcome this challenge, a solvation structure of propylene carbonate (PC)-trifluoromethanesulfonate (Otf)-H2 O is designed and constructed. A K+ /Zn2+ hybrid battery is prepared using MnHCF as cathode, zinc metal as anode, KOTf/Zn(OTf)2 as the electrolyte, and PC as the co-solvent. It is revealed that the addition of PC inhabits the phase transition from MnHCF to ZnHCF, broaden the electrochemical stability window, and inhibits the dendrite growth of zinc metal. Hence, the MnHCF/Zn hybrid co-solvent battery exhibits a reversible capacity of 118 mAh g-1 and high cycling performance, with a capacity retention of 65.6% after 1000 cycles with condition of 1 A g-1 . This work highlights the significance of rationally designing the solvation structure of the electrolyte and promotes the development of high-energy-density of aqueous hybrid ion batteries.
AIMS: Cardiovascular disease is a prevalent worldwide disease, and cardiometabolic risk factors (CMRFs) include hyperlipidemia, hypertension, diabetes, and adiposity. Healthy diets are the critical factor in controlling these CMRFs risks, especially cereal bran which contains many beneficial substances. However, there are still contradictions in the indicators of improving CMRFs by bran from different grain sources or even the same grain source. Therefore, this study aimed to investigate the effects of cereal bran consumption on CMRFs. DATA SYNTHESIS: Eligible randomized controlled studies were searched in PubMed, Embase, Scopus, the Cochrane Library and Web of Science until February 2023. The random-effects model was used to calculate overall effect sizes of weighted mean difference (WMD) and 95% confidence interval (CI). Finally, 22 studies were included in the present meta-analysis. Compared to the control, cereal bran consumption had no significant effect on high-density lipoprotein cholesterol, triglycerides, waist circumference, and body mass index, but could reduce systolic blood pressure (WMD: -1.59; 95% CI: -2.45 to -0.72), diastolic blood pressure (WMD: -1.96; 95% CI: -3.89 to -0.04), total cholesterol (WMD: -0.19; 95% CI: -0.34 to -0.04), low-density lipoprotein cholesterol (WMD: -0.21; 95% CI: -0.38 to -0.04), and fasting blood glucose (WMD: -0.13; 95% CI: -0.24 to -0.01). Additionally, oat bran can lower blood lipids in individuals with lipid diseases and blood pressure in obese or hypertensive patients. CONCLUSIONS: Cereal bran could significantly reduce blood pressure, total cholesterol, low-density lipoprotein cholesterol, and fasting blood glucose in individuals with CMRFs, and oat bran had the most obvious effect.
Cardiovascular Diseases , Edible Grain , Humans , Blood Glucose , Obesity , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cholesterol, LDL , Risk Factors
Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly investigated. It showed that although L-threonine was a main compound of the hexapeptide scaffold of ECB, exogenous addition of L-threonine had no significant effect on the increase of ECB fermentation titer. Meanwhile, the ECB fermentation titer with methyl oleate showed two times higher than that of the other carbon sources. Transcription level analysis of the key genes for ECB biosynthesis indicated that the gene an655543 related to L-threonine biosynthesis showed higher value during the fermentation process, therefore, the exogenous addition of L-threonine had no obvious affection. Furthermore, it indicated that the transcription level of gene ecdA might be the main restriction factor for the ECB biosynthesis. The study provided the research foundation for the modification of the ECB producing strains in the following work.
Antifungal Agents , Echinocandins , Fermentation , Echinocandins/genetics , Echinocandins/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry
Metallic zinc is an ideal anode for aqueous energy storage; however, Zn anodes suffer from nonhomogeneous deposition, low reversibility, and dendrite formation; these lead to an overprovision of zinc metal in full cells. Herein, oriented-attachment-regulated Zn stacking initiated through a trapping-then-planting process with a high zinc utilization rate (ZUR) is reported. Due to the isometric topology features of cubic-type Prussian blue analog (PBA), the initial Zn plating occurs at specific sites with equal spacing of ≈5 Å in the direction perpendicular to the substrate; the trace amount of zinc ions trapped in tunnel matrix provides nuclei for the oriented attachment of Zn (002) deposits. As a result, the PBA-decorated substrate delivers high reversibility of dendrite-free zinc plating/stripping for more than 6600 cycles (1320 h) and achieves an average Coulombic efficiency (CE) of 99.5% at 5 mA cm-2 with 100% ZUR. Moreover, the anode-limited full cell with a low negative-positive electrode ratio (N/P) of 1.2 can be operated stably for 360 cycles, displaying an energy density of 214 Wh kg-1 ; this greatly exceeds commercial aqueous batteries. This work provides a proof of concept design of metal anodes with a high utilization ratio and a practical method for developing high-energy-density batteries.
BACKGROUND: Growing evidence suggests a link between depression and nonalcoholic fatty liver disease (NAFLD). Recently, a change from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. The aim of this study was to determine whether depression scores are associated with newly defined MAFLD as well as liver fibrosis in the US general population. METHODS: This cross-sectional study utilized data from the 2017-March 2020 cycle of the National Health and Nutrition Examination Survey (NHANES) in the US. The depression score was assessed with the Patient Health Questionnaire-9 (PHQ-9). Transient elastography was utilized to evaluate hepatic steatosis and fibrosis with controlled attenuation parameters and liver stiffness measurements, respectively. All the analyses accounted for the complex design parameters and sampling weights of the survey. RESULTS: A total of 3263 eligible subjects aged 20 years and older were included. The estimated prevalence of mild and major depression was 17.0 % (95 % confidence interval [CI]: 14.8-19.3 %) and 7.1 % (6.1-8.1 %), respectively. For every one-unit increase in depression score, a subject was 1.05 (1.02-1.08) times more likely to have MAFLD. Compared to the minimal depression group, those with mild depression had an odds ratio (OR) of 1.54 (1.06-2.25) for MAFLD. The depression score was not associated with clinically significant liver fibrosis. CONCLUSION: The depression score measured by PHQ-9 was independently associated with MAFLD among US adults. LIMITATIONS: Causal relationship is not available due to the cross-sectional nature of the survey design.
Depressive Disorder, Major , Non-alcoholic Fatty Liver Disease , Adult , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Cross-Sectional Studies , Nutrition Surveys , Depression/epidemiology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology
Brain-inspired hardware emulates the structure and working principles of a biological brain and may address the hardware bottleneck for fast-growing artificial intelligence (AI). Current brain-inspired silicon chips are promising but still limit their power to fully mimic brain function for AI computing. Here, we develop Brainoware , living AI hardware that harnesses the computation power of 3D biological neural networks in a brain organoid. Brain-like 3D in vitro cultures compute by receiving and sending information via a multielectrode array. Applying spatiotemporal electrical stimulation, this approach not only exhibits nonlinear dynamics and fading memory properties but also learns from training data. Further experiments demonstrate real-world applications in solving non-linear equations. This approach may provide new insights into AI hardware.
AIMS: The aim was to investigate the effect of mood disorders on parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor disability, substantia nigra pars compacta (SNc) dopaminergic (DA) neurons loss. Also, the neural circuit mechanism was elucidated. METHODS: The depression-like (physical stress, PS) and anxiety-like (emotional stress, ES) mouse models were established by the three-chamber social defeat stress (SDS). The features of Parkinson's disease were reproduced by MPTP injection. Viral-based whole-brain mapping was utilized to resolve the stress-induced global changes in direct inputs onto SNc DA neurons. Calcium imaging and chemogenetic techniques were applied to verify the function of the related neural pathway. RESULTS: We found that PS mice, but not ES mice, showed worse movement performance and more SNc DA neuronal loss than control mice after MPTP administration. The projection from the central amygdala (CeA) to the SNcDA was significantly increased in PS mice. The activity of SNc-projected CeA neurons was enhanced in PS mice. Activating or inhibiting the CeA-SNcDA pathway could mimic or block PS-induced vulnerability to MPTP. CONCLUSIONS: These results indicated that projections from CeA to SNc DA neurons contribute to SDS-induced vulnerability to MPTP in mice.
Disabled Persons , Motor Disorders , Animals , Mice , Humans , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Substantia Nigra , Dopaminergic Neurons/metabolism , Mice, Inbred C57BL , Disease Models, Animal
Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient's response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.
Breast Neoplasms , Humans , Female , Breast Neoplasms/therapy , Immunotherapy/methods
Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.
Drug Delivery Systems , Skin , Animals , Mice , Female , Acute Disease , Drug Delivery Systems/methods , Administration, Cutaneous , Acoustics
OBJECTIVES: The purpose of this study was to systematically analyze the studies of hypertension associated with obstructive sleep apnea to assess the current status and hot spots in this field. METHODS: We searched the Web of Science Core Collection for publications related to hypertension associated with obstructive sleep apnea published before July 3, 2021. Bibliometric analyses and science mappings were carried out using the CiteSpace 5.8.R1 and Microsoft Office Excel 2019. CiteSpace 5.8.R1 was used to visualize the distribution of research fields, analyze co-occurring keywords and burst terms to detect trends and frontiers, and identify leading collaborations among countries, authors, and institutions. Microsoft Office Excel 2019 was used to make bar graphs, histograms and line graphs. RESULTS: According to the search strategy, a total of 7263 published articles and reviews were retrieved. The research on hypertension associated with obstructive sleep apnea has been developing quickly at present. Sleep and Breathing was the most productive journal. The USA was a major producing country and Harvard Medical School was the most productive institution in this field. In the field of hypertension associated with obstructive sleep apnea, the main research hotspots were continuous positive airway pressure, cardiovascular disease, and obesity. CONCLUSIONS: The present study provides a new perspective for the study of hypertension associated with obstructive sleep apnea and valuable information for researchers to find potential partners and cooperative institutions, hot issues and research frontiers.
Cardiovascular Diseases , Hypertension , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Respiration , Bibliometrics
A process accumulated record solar to hydrogen (STH) conversion efficiency of 8% is achieved on the Cu2 ZnSnS4 -BiVO4 tandem cell by the synergistic coupling effect of solar thermal and photoelectrochemical (PEC) water splitting with the dynamic balance of solar energy storage and conversion of the greenhouse system. This is the first report of a Cu2 ZnSnS4 -BiVO4 tandem cell with a high unbiased STH efficiency of over 8% for solar water splitting due to the greenhouse device system. The greenhouse acts as a solar thermal energy storage cell, which absorbs infrared solar light and storage as thermal energy with the solar light illumination time, while thermoelectric device (TD) converts thermal energy into electric power, electric power is also recycled and added onto Cu2 ZnSnS4 -BiVO4 tandem cell for enhanced overall water splitting. Finally, the solar water splitting properties of the TD-Cu2 ZnSnS4 -BiVO4 integrated tandem cell in pure natural seawater are demonstrated, and a champion STH efficiency of 2.46% is presented, while a large area (25 cm2 ) TD-Cu2 ZnSnS4 -BiVO4 integrated tandem device with superior long-term stability is investigated for 1 week, which provides new insight into photoelectrochemical solar water splitting devices.
pioids are commonly used for treating chronic pain. However, with continued use, they may induce tolerance and/or hyperalgesia, which limits therapeutic efficacy. The human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied, in part, because current models cannot fully recapitulate human pathology. Here, we engineered novel human spinal microphysiological systems (MPSs) integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced tolerance. Each spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity measurement. We found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids, but also promotes their neuron maturation, neural activity, and functional development. We further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia, as measured by altered neural activity, and downregulation of µ-opioid receptor expression of human spinal MPSs. The MPSs are scalable, cost-effective, easy-to-use, and compatible with commonly-used well-plates, thus allowing plug-and-play measurements of neural activity. We believe the MPSs hold a promising translational potential for studying human pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.
