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1.
Plant Sci ; : 112226, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153574

RESUMO

Teosinte is a progenitor species of maize (Zea mays ssp. mays) that retains a significant reservoir of genetic resources unaltered via the domestication process. To harness and explore the genetic reservoirs inherent in teosinte, we used the cultivated publicly inbred line H95 and wild species PI566673 (Zea mays ssp. mexicana) to develop a set of introgression lines (ILs), including 366 BC2F5 lines. Using these lines, 12481 high-quality polymorphic homozygous single nucleotide polymorphisms were converted into 2358 bin markers based on Genotyping by Target Sequencing technology. The homozygous introgression ratio in the ILs was approximately 12.1% and the heterozygous introgression ratio was approximately 5.7%. Based on the population phenotypic data across 21 important agronomic traits collected in Sanya and Beijing, 185 and 156 quantitative trait loci (QTLs) were detected in Sanya and Beijing, respectively, with 64 stable QTLs detected in both locations. We detected 12 QTL clusters spanning 10 chromosomes consisting of diverse QTLs related to yield traits such as grain size and weight. In addition, we identified useful materials in the ILs for further gene cloning of related variations. For example, some heterogeneous inbred families with superior genetic purity, shorter target heterozygotes, and some ILs exhibit clear morphological variation associated with plant growth, development, and domestication, manifesting traits such as white stalks, sharp seeds, and cob shattering. In conclusion, our results provide a robust foundation for delving into the genetic reservoirs of teosinte, presenting a wealth of genetic resources and offering insight into the genetic architecture underlying maize agronomic traits.

2.
Drug Metab Pharmacokinet ; 58: 101031, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39146603

RESUMO

Substance use disorders (SUDs) are complex mental health conditions involving a problematic pattern of substance use. Challenges remain in understanding their neural mechanisms, which are likely to lead to improved SUD treatments. Human brain organoids, brain-like 3D in vitro cultures derived from human stem cells, show unique potential in recapitulating the response of a developing human brain to substances. Here, we review the recent progress in understanding SUDs using human brain organoid models focusing on neurodevelopmental perspectives. We first summarize the background of SUDs in humans. Moreover, we introduce the development of various human brain organoid models and then discuss current progress and findings underlying the abuse of substances like nicotine, alcohol, and other addictive drugs using organoid models. Furthermore, we review efforts to develop organ chips and microphysiological systems to engineer better human brain organoids for advancing SUD studies. Lastly, we conclude by elaborating on the current challenges and future directions of SUD studies using human brain organoids.

3.
Sci Total Environ ; 947: 174478, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38964381

RESUMO

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Mesencéfalo , Organoides , Fluorocarbonos/toxicidade , Humanos , Ácidos Alcanossulfônicos/toxicidade , Organoides/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Gravidez , Feminino , Sistemas Microfisiológicos
4.
Langmuir ; 40(25): 13092-13101, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38872614

RESUMO

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.

5.
J Clin Nurs ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706438

RESUMO

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.

6.
Nano Res ; 17(2): 462-475, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38712329

RESUMO

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.

7.
Materials (Basel) ; 17(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38612209

RESUMO

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.

8.
bioRxiv ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38617279

RESUMO

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.

9.
Small ; 20(29): e2310997, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38353064

RESUMO

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 Na3Al2/3V4/3(PO4)3(NAVP) microspheres (Na3Al2/3V4/3(PO4)2.9F0.3(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.

10.
Immunol Invest ; 52(7): 925-939, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37732637

RESUMO

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.


Assuntos
Lesão Pulmonar Aguda , Edema Pulmonar , Animais , Humanos , Camundongos , Células A549 , Lesão Pulmonar Aguda/induzido quimicamente , Canais Epiteliais de Sódio/genética , Lipopolissacarídeos
11.
Sci Data ; 10(1): 617, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37696817

RESUMO

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.

12.
Small Methods ; : e2300617, 2023 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-37423947

RESUMO

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.

13.
Nutr Metab Cardiovasc Dis ; 33(10): 1849-1865, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37482485

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Grão Comestível , Humanos , Glicemia , Obesidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Fatores de Risco
14.
Bioprocess Biosyst Eng ; 46(7): 1045-1052, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37253987

RESUMO

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.


Assuntos
Antifúngicos , Equinocandinas , Fermentação , Equinocandinas/genética , Equinocandinas/química , Antifúngicos/farmacologia , Antifúngicos/química
15.
Adv Mater ; 35(33): e2302353, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37145988

RESUMO

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.

16.
J Affect Disord ; 334: 332-336, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37142003

RESUMO

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.


Assuntos
Transtorno Depressivo Maior , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Transversais , Inquéritos Nutricionais , Depressão/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia
17.
CNS Neurosci Ther ; 29(7): 1940-1952, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36914579

RESUMO

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.


Assuntos
Pessoas com Deficiência , Transtornos Motores , Animais , Camundongos , Humanos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Substância Negra , Neurônios Dopaminérgicos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
18.
bioRxiv ; 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36909615

RESUMO

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.

19.
Nat Commun ; 14(1): 869, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797284

RESUMO

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.


Assuntos
Sistemas de Liberação de Medicamentos , Pele , Animais , Camundongos , Feminino , Doença Aguda , Sistemas de Liberação de Medicamentos/métodos , Administração Cutânea , Acústica
20.
J Nanobiotechnology ; 21(1): 40, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739414

RESUMO

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.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Imunoterapia/métodos
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