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1.
Sensors (Basel) ; 24(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38931613

ABSTRACT

In the autonomous driving industry, there is a growing trend to employ long-wave infrared (LWIR)-based uncooled thermal-imaging cameras, capable of robustly collecting data even in extreme environments. Consequently, both industry and academia are actively researching contrast-enhancement techniques to improve the quality of LWIR-based thermal-imaging cameras. However, most research results only showcase experimental outcomes using mass-produced products that already incorporate contrast-enhancement techniques. Put differently, there is a lack of experimental data on contrast enhancement post-non-uniformity (NUC) and temperature compensation (TC) processes, which generate the images seen in the final products. To bridge this gap, we propose a histogram equalization (HE)-based contrast enhancement method that incorporates a region-based clipping technique. Furthermore, we present experimental results on the images obtained after applying NUC and TC processes. We simultaneously conducted visual and qualitative performance evaluations on images acquired after NUC and TC processes. In the visual evaluation, it was confirmed that the proposed method improves image clarity and contrast ratio compared to conventional HE-based methods, even in challenging driving scenarios such as tunnels. In the qualitative evaluation, the proposed method demonstrated upper-middle-class rankings in both image quality and processing speed metrics. Therefore, our proposed method proves to be effective for the essential contrast enhancement process in LWIR-based uncooled thermal-imaging cameras intended for autonomous driving platforms.

2.
Biomimetics (Basel) ; 9(6)2024 May 22.
Article in English | MEDLINE | ID: mdl-38921191

ABSTRACT

This study investigated the locomotion mechanism of foxtail robots, focusing on the frictional anisotropy of tilted bristles under the same friction coefficient and propulsion strategy using bristle diversity. Through dynamic analysis and simulations, we confirmed the frictional anisotropy of tilted bristles and elucidated the role of bristle diversity in generating propulsive force. The interaction between contact nonuniformity and frictional anisotropy was identified as the core principle enabling foxtail locomotion. Simulations of foxtail robots with multiple bristles demonstrated that variations in bristle length, angle, and deformation contribute to propulsive force generation and environmental adaptability. In addition, this study analyzed the influence of major design parameters on frictional anisotropy, highlighting the critical roles of body height, bristle length, stiffness, reference angle, and friction coefficient. The proposed guidelines for designing foxtail robots emphasize securing bristle nonuniformity and inducing contact nonuniformity. The simulation framework presented enables the quantitative prediction and optimization of foxtail robot performance. This research provides valuable insights into foxtail robot locomotion and lays a foundation for the development of efficient and adaptive next-generation robots for diverse environments.

3.
Nat Commun ; 15(1): 4349, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834548

ABSTRACT

Stretchable organic light-emitting diodes (OLEDs) have emerged as promising optoelectronic devices with exceptional degree of freedom in form factors. However, stretching OLEDs often results in a reduction in the geometrical fill factor (FF), that is the ratio of an active area to the total area, thereby limiting their potential for a broad range of applications. To overcome these challenges, we propose a three-dimensional (3D) architecture adopting a hidden active area that serves a dual role as both an emitting area and an interconnector. For this purpose, an ultrathin OLED is first attached to a 3D rigid island array structure through quadaxial stretching for precise, deformation-free alignment. A portion of the ultrathin OLED is concealed by letting it 'fold in' between the adjacent islands in the initial, non-stretched condition and gradually surfaces to the top upon stretching. This design enables the proposed stretchable OLEDs to exhibit a relatively high FF not only in the initial state but also after substantial deformation corresponding to a 30% biaxial system strain. Moreover, passive-matrix OLED displays that utilize this architecture are shown to be configurable for compensation of post-stretch resolution loss, demonstrating the efficacy of the proposed approach in realizing the full potential of stretchable OLEDs.

4.
Medicine (Baltimore) ; 103(19): e38168, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728455

ABSTRACT

BACKGROUND: Supplementation with leucine-enriched essential amino acids (LEAAs) has shown efficacy in the recovery of muscle injury and activation of muscle synthesis. Muscle function in knee osteoarthritis is a crucial factor for managing pain and preserving ambulatory function. However, the efficacy and safety of LEAAs supplementation in patients with knee osteoarthritis have not been evaluated. METHODS: In this prospective analysis, we evaluated the efficacy and safety of supplementation with 12 g of LEAAs daily for 8 weeks in knee-symptomatic osteoarthritis patients. For assessing the efficacy, clinical pain, calf circumference, and disability were assessed using questionnaires (visual analog scale, Knee Society Score, and 36-item short form survey [SF-36]), laboratory analyses (total protein and albumin), and radiologic study (dual-energy X-ray absorptiometry [DEXA]) for muscle and bone density. To evaluate safety, generalized or localized protein allergic reactions, complete blood count, liver and kidney function, and serum glucose were measured. RESULTS: Sixty-five participants, categorized into the experimental (n = 32) and control (n = 33) groups, were included in this 8-week trial from March 2022 to July 2022. A significantly higher efficacy was observed in the experimental group than in the control group, as indicated by muscle density in the DEXA scan (P = .001) and SF-36 (P < .001). The safety evaluation revealed no related generalized or local protein allergy. Hematological findings, serum glucose, and kidney and liver toxicity were not significantly different between the groups. CONCLUSION: Supplementation with leucine-enriched proteins is safe and efficacious in the improvement of muscle density and quality of life.


Subject(s)
Amino Acids, Essential , Dietary Supplements , Leucine , Osteoarthritis, Knee , Humans , Female , Osteoarthritis, Knee/drug therapy , Leucine/therapeutic use , Leucine/administration & dosage , Male , Middle Aged , Amino Acids, Essential/therapeutic use , Amino Acids, Essential/administration & dosage , Prospective Studies , Aged , Treatment Outcome , Pain Measurement
5.
Sci Adv ; 10(20): eadn8465, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758786

ABSTRACT

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

6.
Front Microbiol ; 15: 1355599, 2024.
Article in English | MEDLINE | ID: mdl-38706966

ABSTRACT

The emergence of anti-influenza drug-resistant strains poses a challenge for influenza therapy due to mutations in the virus's surface protein. Recently, there has been increasing interest in combination therapy consisting of two or more drugs as a potential alternative approach, aiming to enhance therapeutic efficacy. In this study, we investigated a novel synergistic therapy with a vertical effect using a single-domain VL-HA1-specific antibody against H1N1/PR8 and a horizontal effect using an RNA catalytic antibody with broad-spectrum influenza antiviral drug. We isolated a single-domain VL-HA1-specific (NVLH8) antibody binding to the virus particles showing a neutralizing activity against influenza virus A, specifically H1N1/PR8, as determined by the reduction in plaque number and lower viral HA protein expression in vitro. The neutralizing antibody likely prevented the viral entry, specifically at the viral genome-releasing step. Additionally, the 3D8 scFv hydrolyzed viral RNAs in the cytoplasm, including mRNA, vRNA, and cRNA in MDCK cells. The combined treatment of neutralizing antibodies for a vertical effect and 3D8 scFv for a horizontal effect produced a synergistic effect providing a novel approach against viral diseases when compared with a single treatment. Our results indicated that combining treatment, in particular two proteins exhibiting different mechanisms of action increased the antiviral activity against the influenza virus.

7.
Sensors (Basel) ; 24(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732934

ABSTRACT

In the field of robotics and autonomous driving, dynamic occupancy grid maps (DOGMs) are typically used to represent the position and velocity information of objects. Although three-dimensional light detection and ranging (LiDAR) sensor-based DOGMs have been actively researched, they have limitations, as they cannot classify types of objects. Therefore, in this study, a deep learning-based camera-LiDAR sensor fusion technique is employed as input to DOGMs. Consequently, not only the position and velocity information of objects but also their class information can be updated, expanding the application areas of DOGMs. Moreover, unclassified LiDAR point measurements contribute to the formation of a map of the surrounding environment, improving the reliability of perception by registering objects that were not classified by deep learning. To achieve this, we developed update rules on the basis of the Dempster-Shafer evidence theory, incorporating class information and the uncertainty of objects occupying grid cells. Furthermore, we analyzed the accuracy of the velocity estimation using two update models. One assigns the occupancy probability only to the edges of the oriented bounding box, whereas the other assigns the occupancy probability to the entire area of the box. The performance of the developed perception technique is evaluated using the public nuScenes dataset. The developed DOGM with object class information will help autonomous vehicles to navigate in complex urban driving environments by providing them with rich information, such as the class and velocity of nearby obstacles.

8.
Sci Rep ; 14(1): 6847, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38514797

ABSTRACT

Entangled coherent states play pivotal roles in various fields such as quantum computation, quantum communication, and quantum sensing. We experimentally demonstrate the generation of entangled coherent states with the two-dimensional motion of a trapped ion system. Using Raman transitions with appropriate detunings, we simultaneously drive the red and blue sidebands of the two transverse axes of a single trapped ion and observe multi-periodic entanglement and disentanglement of its spin and two-dimensional motion. Then, by measuring the spin state, we herald entangled coherent states of the transverse motions of the trapped ion and observe the corresponding modulation in the parity of the phonon distribution of one of the harmonic oscillators. Lastly, we trap two ions in a linear chain and realize Mølmer-Sørensen gate using two-dimensional motion.

9.
NPJ Vaccines ; 9(1): 68, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38555379

ABSTRACT

Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.

10.
Sci Transl Med ; 16(737): eadf4601, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38446899

ABSTRACT

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or "chemobrain," which can persist for the remainder of their lives. Despite the growing prevalence of chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics with neurodegenerative diseases, including chronic neuroinflammation, DNA damage, and synaptic loss. We investigated whether a noninvasive sensory stimulation treatment we term gamma entrainment using sensory stimuli (GENUS), which has been shown to alleviate aberrant immune and synaptic pathologies in mouse models of neurodegeneration, could also mitigate chemobrain phenotypes in mice administered a chemotherapeutic drug. When administered concurrently with the chemotherapeutic agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, and improved cognitive function in a mouse model of chemobrain. These effects persisted for up to 105 days after GENUS treatment, suggesting the potential for long-lasting benefits. However, when administered to mice 90 days after chemotherapy, GENUS treatment only provided limited benefits, indicating that it was most effective when used to prevent the progression of chemobrain pathology. Furthermore, we demonstrated that the effects of GENUS in mice were not limited to cisplatin-induced chemobrain but also extended to methotrexate-induced chemobrain. Collectively, these findings suggest that GENUS may represent a versatile approach for treating chemobrain induced by different chemotherapy agents.


Subject(s)
Chemotherapy-Related Cognitive Impairment , Cognitive Dysfunction , Humans , Animals , Mice , Cisplatin/adverse effects , Cognition , DNA Damage , Disease Models, Animal
11.
Nature ; 627(8002): 149-156, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38418876

ABSTRACT

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.


Subject(s)
Alzheimer Disease , Amyloid , Brain , Cerebrospinal Fluid , Extracellular Fluid , Gamma Rhythm , Glymphatic System , Animals , Mice , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/prevention & control , Amyloid/metabolism , Aquaporin 4/metabolism , Astrocytes/metabolism , Brain/cytology , Brain/metabolism , Brain/pathology , Cerebrospinal Fluid/metabolism , Disease Models, Animal , Extracellular Fluid/metabolism , Glymphatic System/physiology , Interneurons/metabolism , Vasoactive Intestinal Peptide/metabolism , Cerebral Cortex/cytology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Electric Stimulation
12.
J Gynecol Oncol ; 35(2): e66, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38330382

ABSTRACT

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.


Subject(s)
Endometrial Neoplasms , Genital Neoplasms, Female , Ovarian Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Genital Neoplasms, Female/drug therapy , Ovarian Neoplasms/pathology , Endometrial Neoplasms/drug therapy
13.
Commun Med (Lond) ; 4(1): 19, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38366141

ABSTRACT

BACKGROUND: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. METHODS: We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. RESULTS: COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. CONCLUSIONS: These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.


Mpox is an ilness caused by the mpox virus (MPXV) that belongs to the poxvirus family. The 2022-2023 mpox outbreak highlights the need to develop effective vaccines against MPXV. We have developed a COVID-19 vaccine using as scaffold chemically synthesized genetic material of a highly attenuated and safe poxvirus vector. This scaffold is the same present in a vaccine that has been approved and is given to prevent mpox. Here, we show that healthy human volunteers or monkeys vaccinated with this COVID-19 vaccine generated a robust immune response against MPXV, similar to that generated by the mpox vaccine with the same scaffold. This COVID-19 vaccine is also able to protect mice from infection caused by the MPXV strain isolated from the recent mpox outbreak. This COVID-19 vaccine in a poxvirus scaffold might be an additional tool to curtail mpox outbreaks.

14.
Cell Host Microbe ; 32(2): 244-260.e11, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38198924

ABSTRACT

Although early life colonization of commensal microbes contributes to long-lasting immune imprinting in host tissues, little is known regarding the pathophysiological consequences of postnatal microbial tuning of cutaneous immunity. Here, we show that postnatal exposure to specific skin commensal Staphylococcus lentus (S. lentus) promotes the extent of atopic dermatitis (AD)-like inflammation in adults through priming of group 2 innate lymphoid cells (ILC2s). Early postnatal skin is dynamically populated by discrete subset of primed ILC2s driven by microbiota-dependent induction of thymic stromal lymphopoietin (TSLP) in keratinocytes. Specifically, the indole-3-aldehyde-producing tryptophan metabolic pathway, shared across Staphylococcus species, is involved in TSLP-mediated ILC2 priming. Furthermore, we demonstrate a critical contribution of the early postnatal S. lentus-TSLP-ILC2 priming axis in facilitating AD-like inflammation that is not replicated by later microbial exposure. Thus, our findings highlight the fundamental role of time-dependent neonatal microbial-skin crosstalk in shaping the threshold of innate type 2 immunity co-opted in adulthood.


Subject(s)
Dermatitis, Atopic , Thymic Stromal Lymphopoietin , Humans , Adult , Infant, Newborn , Immunity, Innate , Lymphocytes , Cytokines/metabolism , Skin/metabolism , Inflammation
15.
J Gynecol Oncol ; 35(2): e18, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37921602

ABSTRACT

OBJECTIVE: To assess the frequency of regular uptake of national cervical cancer screening (CCS) program and identify associated factors among Korean women. METHODS: This study is a fundamental investigation that employs openly accessible public data of Korea through secondary data analysis. A cohort of 4,663 women from the 2007-2012 Korean National Health and Nutrition Examination Survey, was followed up for up to 12 years (2007-2018) to obtain the frequency of national CCS. Compliance level with CCS was categorized, and an ordinal logistic regression model was employed to investigate the contributing factors. RESULTS: The regular uptake of CCS in South Korea was low at 18.9%. The trend of regular screening showed significant association with various factors, including age (40-59 years), household income (100%-150% bracket), occupation (service workers), place of residence (small to medium sized cities), education level (middle school graduates), marital status (married), and possession of private insurance. Moreover, individuals with a history of non-cervical cancer or carcinoma in situ of the cervix, a family history of cervical cancer, or a higher frequency of general check-ups demonstrated a stronger adherence to regular CCS uptake. CONCLUSION: Our findings revealed that regular participation in CCS in Korea was lower than anticipated, with factors such as socioeconomic status, personal history of gynecologic issue, and frequency of general health check-ups playing influential roles. However, further research, including an exploration of unexamined psychological barriers to screening, is necessary to gain a better understanding the reasons behind the reduced rates of regular CCS among Korean women.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Nutrition Surveys , Early Detection of Cancer , Mass Screening , Republic of Korea/epidemiology
16.
Neuron ; 112(2): 201-208.e4, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-37944516

ABSTRACT

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA). These neurons are activated during fear memory formation and exhibit a preference for forming synapses with excitatory engram neurons. Post-activation, these SOM neurons displayed varying excitability based on fear memory retrieval. Furthermore, when we modulated these SOM neurons chemogenetically, we observed changes in the expression of fear-related behaviors, both in a fear-associated context and in a novel setting. Our findings suggest that these activated SOM interneurons play a pivotal role in modulating engram cell activity. They influence the expression of fear-related behaviors through a mechanism that is dependent on memory cues.


Subject(s)
Basolateral Nuclear Complex , Interneurons , Mice , Animals , Interneurons/physiology , Memory/physiology , Neurons/physiology , Basolateral Nuclear Complex/physiology , Somatostatin/metabolism
17.
J Control Release ; 365: 703-715, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38016489

ABSTRACT

Recently, CRISPR proteins have been recognized as promising candidates for drug development. However, there is still a lack of substances with the appropriate sensitivity and stability for targeted drug delivery systems. 89Zr is a radioactive isotope that emits positrons, allowing real-time in vivo tracking with proven safety. In this study, we confirmed that labeling with 89Zr did not compromise the functionality of CRISPR proteins during in vivo behavioral imaging. Furthermore, we demonstrated the therapeutic efficacy of the CRISPR interference system in a mouse model of liver fibrosis, highlighting the theragnostic potential of isotope-labeled CRISPR proteins. The findings of this research could contribute to various aspects of ongoing clinical studies exploring the in vivo applications of CRISPR proteins.


Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , Positron-Emission Tomography , Mice , Animals , Positron-Emission Tomography/methods , Zirconium , Radioisotopes , Tissue Distribution , Isotope Labeling
18.
Proc Natl Acad Sci U S A ; 120(52): e2309786120, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38109550

ABSTRACT

Many sub-Neptune exoplanets have been believed to be composed of a thick hydrogen-dominated atmosphere and a high-temperature heavier-element-dominant core. From an assumption that there is no chemical reaction between hydrogen and silicates/metals at the atmosphere-interior boundary, the cores of sub-Neptunes have been modeled with molten silicates and metals (magma) in previous studies. In large sub-Neptunes, pressure at the atmosphere-magma boundary can reach tens of gigapascals where hydrogen is a dense liquid. A recent experiment showed that hydrogen can induce the reduction of Fe[Formula: see text] in (Mg,Fe)O to Fe[Formula: see text] metal at the pressure-temperature conditions relevant to the atmosphere-interior boundary. However, it is unclear whether Mg, one of the abundant heavy elements in the planetary interiors, remains oxidized or can be reduced by H. Our experiments in the laser-heated diamond-anvil cell found that heating of MgO + Fe to 3,500 to 4,900 K (close to or above their melting temperatures) in an H medium leads to the formation of Mg[Formula: see text]FeH[Formula: see text] and H[Formula: see text]O at 8 to 13 GPa. At 26 to 29 GPa, the behavior of the system changes, and Mg-H in an H fluid and H[Formula: see text]O were detected with separate FeH[Formula: see text]. The observations indicate the dissociation of the Mg-O bond by H and subsequent production of hydride and water. Therefore, the atmosphere-magma interaction can lead to a fundamentally different mineralogy for sub-Neptune exoplanets compared with rocky planets. The change in the chemical reaction at the higher pressures can also affect the size demographics (i.e., "radius cliff") and the atmosphere chemistry of sub-Neptune exoplanets.

19.
Sci Adv ; 9(50): eadi6096, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38100581

ABSTRACT

Giant impact-driven redox processes in the atmosphere and magma ocean played crucial roles in the evolution of Earth. However, because of the absence of rock records from that time, understanding these processes has proven challenging. Here, we present experimental results that simulate the giant impact-driven reactions between iron and volatiles (H2O and CO2) using x-ray free electron laser (XFEL) as fast heat pump and structural probe. Under XFEL pump, iron is oxidized to wüstite (FeO), while volatiles are reduced to H2 and CO. Furthermore, iron oxidation proceeds into formation of hydrides (γ-FeHx) and siderite (FeCO3), implying redox boundary near 300-km depth. Through quantitative analysis on reaction products, we estimate the volatile and FeO budgets in bulk silicate Earth, supporting the Theia hypothesis. Our findings shed light on the fast and short-lived process that led to reduced atmosphere, required for the emergence of prebiotic organic molecules in the early Earth.

20.
Exp Mol Med ; 55(11): 2461-2472, 2023 11.
Article in English | MEDLINE | ID: mdl-37919422

ABSTRACT

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.


Subject(s)
Caveolin 1 , Stomach Neoplasms , Humans , Caveolin 1/genetics , Caveolin 1/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Down-Regulation , Endocytosis
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