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1.
Cell ; 187(11): 2855-2874.e19, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38657603

RESUMEN

Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.


Asunto(s)
Embrión de Mamíferos , Gastrulación , Regulación del Desarrollo de la Expresión Génica , Imagenología Tridimensional , Humanos , Embrión de Mamíferos/metabolismo , Transcriptoma/genética , Gástrula/metabolismo , Gástrula/embriología , Transducción de Señal , Linaje de la Célula , Perfilación de la Expresión Génica , Tipificación del Cuerpo/genética
2.
Cell ; 187(3): 764-781.e14, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38306985

RESUMEN

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.


Asunto(s)
Metabolómica , Embarazo , Animales , Femenino , Humanos , Embarazo/metabolismo , Corticosterona/metabolismo , Metaboloma/fisiología , Placenta/metabolismo , Preeclampsia , Primates/metabolismo
3.
Nature ; 612(7941): 732-738, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36517595

RESUMEN

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.


Asunto(s)
Gastrulación , Macaca fascicularis , Organogénesis , Análisis de la Célula Individual , Animales , Humanos , Ratones , Gastrulación/genética , Macaca fascicularis/embriología , Macaca fascicularis/genética , Organogénesis/genética , Cuerpos Embrioides , Perfilación de la Expresión Génica , Línea Primitiva/citología , Línea Primitiva/embriología , Tubo Neural/citología , Tubo Neural/embriología , Cresta Neural/citología , Cresta Neural/embriología , Vía de Señalización Hippo , Mesodermo/citología , Mesodermo/embriología , Células Madre
4.
Cell Mol Life Sci ; 81(1): 187, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38635081

RESUMEN

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.


Asunto(s)
Fibrosis Pulmonar Idiopática , Macrófagos , Canal Catiónico TRPA1 , Animales , Ratones , Acetanilidas , Bleomicina , Colágeno , Proteínas del Citoesqueleto , Ratones Endogámicos C57BL , Purinas , Canal Catiónico TRPA1/metabolismo
5.
J Transl Med ; 22(1): 771, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148053

RESUMEN

BACKGROUND: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown. METHODS: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker® probes, mitochondrial stress, real-time ATP rate and western blotting. RESULTS: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3ß signaling pathway to inhibit mitochondria-dependent neuronal apoptosis. CONCLUSION: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis.


Asunto(s)
Apoptosis , Supervivencia Celular , Metilhidrazinas , Mitocondrias , Neuronas , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Fármacos Neuroprotectores/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Daño por Reperfusión/patología , Daño por Reperfusión/tratamiento farmacológico , Masculino , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Metilhidrazinas/farmacología , Metilhidrazinas/uso terapéutico , Isquemia Encefálica/patología , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas
6.
Cell Commun Signal ; 22(1): 383, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075489

RESUMEN

BACKGROUND: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. METHODS: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. RESULTS: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. CONCLUSION: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.


Asunto(s)
Lesiones Encefálicas , Fosfoglicerato Quinasa , Animales , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Quinasa/genética , Ratones , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Hipoxia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo
7.
Inorg Chem ; 63(17): 7926-7936, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38621361

RESUMEN

Heteroatom doping and heterostructure construction are the key methods to improve the performance of electrocatalysts. However, developing such catalysts remains a challenging task. Herein, we designed two comparable polymers, phytic acid/thiourea polymer (PATP) and phytic acid/urea polymer (PAUP), as precursors, which contain C, N, S/O, and P by microwave heating. To pinpoint how the introduction of sulfur would affect the electronic structure and catalytic activity, these two polymers were physically blended with CoCo-Prussian blue analogue (CoCo-PBA) and further calcination, respectively. The highly dispersed CoP/Co2P-rich interfacial catalysts anchored on the N,S-codoped or N-doped carbon support were successfully prepared (CoP/Co2P@CNS and CoP/Co2P@CN). The prepared CoP/Co2P@CNS catalyst showed good ORR properties (E1/2 = 0.856 V vs RHE) and OER properties (Ej10 = 1.54 V vs RHE), which were superior to the commercial Pt/C and RuO2 catalysts. The reversible oxygen electrode index (ΔE = Ej10 - E1/2) can reach ∼0.684 V. Meanwhile, the rechargeable zinc-air battery assembled with a CoP/Co2P@CNS catalyst as the air cathode also showed excellent performance, with a charge-discharge cycle stability of up to 900 h. DFT calculations further confirm that the introduction of S atoms can affect the electronic structure and enhance the catalytic activity of C and N atoms on carbon support.

8.
Inorg Chem ; 63(33): 15477-15484, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39105705

RESUMEN

Transition-metal phosphides (TMPs) have attracted extensive attention in energy-related fields, especially for electrocatalytic hydrogen evolution reaction (HER). However, it is imperative to develop a facile and time-consuming approach to prepare metal phosphides with satisfactory catalytic performance. Herein, nitrogen-doped CoP-Co2P decorated with Ru (Ru/N-CoP-Co2P) is synthesized (Ru/N-CoP-Co2P) through a hydrothermal route and following an ultrafast and simple microwave avenue within 20 s. The achieved Ru/N-CoP-Co2P possesses an interconnected porous morphology to expose abundant active sites and accelerate the mass transport. Moreover, N doping and Ru-supported decorated Ru/N-CoP-Co2P also play a key role in promoting the electrocatalytic activity. Therefore, the as-designed Ru/N-CoP-Co2P presents good catalytic performance for the HER in a wide pH range. Ru/N-CoP-Co2P merely needs overpotentials of 63, 100, and 65 mV to obtain 10 mA cm-2 in acidic, alkaline, and seawater electrolytes. This research provides a novel and efficient strategy for the synthesis of TMPs with highly efficient catalytic activity.

9.
Bioorg Chem ; 148: 107475, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38772293

RESUMEN

The applications of antisense oligonucleotides (ASOs) in rare or common diseases treatment have garnered great attention in recent years. Nevertheless, challenges associated with stability and bioavailability still persist, hampering the efficiency of ASOs. This work presents an ASO prodrug with parallel G-quadruplex assembly and lysosome escape capabilities for oncotherapy. Our findings revealed that the end-assembled quadruplex structure effectively shielded the ASO from enzymatic degradation. Meanwhile, the conjugation of maleimide within the quadruplex enhanced cellular uptake, potentially offering an alternative cell entry mechanism that circumvents lysosome involvement. Notably, an optimized molecule, Mal2-G4-ASO, exhibited remarkable therapeutic effects both in vitro and in vivo. This work presents a promising avenue for enhancing the activity of nucleic acid drugs in oncotherapy and potentially other disease contexts.


Asunto(s)
G-Cuádruplex , Lisosomas , Oligonucleótidos Antisentido , Profármacos , Profármacos/química , Profármacos/farmacología , Profármacos/síntesis química , G-Cuádruplex/efectos de los fármacos , Humanos , Oligonucleótidos Antisentido/química , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/síntesis química , Lisosomas/metabolismo , Animales , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ratones , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Línea Celular Tumoral , Ratones Desnudos , Ratones Endogámicos BALB C
10.
Sensors (Basel) ; 24(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38894072

RESUMEN

The large amount of sampled data in coherent phase-sensitive optical time-domain reflectometry (Φ-OTDR) brings heavy data transmission, processing, and storage burdens. By using the comparator combined with undersampling, we achieve simultaneous reduction of sampling rate and sampling resolution in hardware, thus greatly decreasing the sampled data volume. But this way will inevitably cause the deterioration of detection signal-to-noise ratio (SNR) due to the quantization noise's dramatic increase. To address this problem, denoising the demodulated phase signals using compressed sensing, which exploits the sparsity of spectrally sparse vibration, is proposed, thereby effectively enhancing the detection SNR. In experiments, the comparator with a sampling parameter of 62.5 MS/s and 1 bit successfully captures the 80 MHz beat signal, where the sampled data volume per second is only 7.45 MB. Then, when the piezoelectric transducer's driving voltage is 1 Vpp, 300 mVpp, and 100 mVpp respectively, the SNRs of the reconstructed 200 Hz sinusoidal signals are respectively enhanced by 23.7 dB, 26.1 dB, and 28.7 dB by using compressed sensing. Moreover, multi-frequency vibrations can also be accurately reconstructed with a high SNR. Therefore, the proposed technique can effectively enhance the system's performance while greatly reducing its hardware burden.

11.
HPB (Oxford) ; 26(6): 753-763, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38485565

RESUMEN

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Puntaje de Propensión , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Masculino , Femenino , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estimación de Kaplan-Meier
12.
Phys Rev Lett ; 131(5): 056301, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37595207

RESUMEN

We study quantum phase transitions of three-dimensional disordered systems in the chiral classes (AIII and BDI) with and without weak topological indices. We show that the systems with a nontrivial weak topological index universally exhibit an emergent thermodynamic phase where wave functions are delocalized along one spatial direction but exponentially localized in the other two spatial directions, which we call the quasilocalized phase. Our extensive numerical study clarifies that the critical exponent of the Anderson transition between the metallic and quasilocalized phases, as well as that between the quasilocalized and localized phases, are different from that with no weak topological index, signaling the new universality classes induced by topology. The quasilocalized phase and concomitant topological Anderson transition manifest themselves in the anisotropic transport phenomena of disordered weak topological insulators and nodal-line semimetals, which exhibit the metallic behavior in one direction but the insulating behavior in the other directions.

13.
Am J Hematol ; 98(9): 1407-1414, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37421604

RESUMEN

The Phase 3 single-arm COMMODORE 3 study (ClinicalTrials.gov, NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor-naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every-4-weeks subcutaneous maintenance doses per weight-based tiered-dosing schedule. Co-primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15-58 years old) were enrolled; all received treatment. At primary analysis, both co-primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8-86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant (p < .0001). No adverse events led to treatment discontinuation. One treatment-unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every-4-weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor-naive patients with PNH.


Asunto(s)
Hemoglobinuria Paroxística , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/efectos adversos , Inactivadores del Complemento/efectos adversos , Hemólisis , Anticuerpos Monoclonales/uso terapéutico , Complemento C5
14.
Inorg Chem ; 62(24): 9687-9694, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37267518

RESUMEN

Molybdenum phosphide (MoP) has received increasing attention for the hydrogen evolution reaction (HER) due to its Pt-like electronic structure and high electrical conductivity. In this work, a flake-like Ru-doped MoP with phosphorus vacancy (Ru-MoP-PV) electrocatalyst is synthesized for the first time by a simple and rapid room-temperature microwave approach within 30 s. The created abundant phosphorus vacancies provide rich active sites and favor rapid electron transfer. The introduced Ru also enhances the catalytic activity of the synthesized electrocatalyst efficiently. Then, the designed Ru-MoP-PV possesses low overpotentials for HER with 79, 100, and 161 mV in 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline to obtain 10 mA cm-2. The Ru-MoP-PV and NiFe-layered double hydroxide are used as the cathode and the anode, respectively, to drive water splitting and just need a low cell voltage of 1.6 V to achieve 10 mA cm-2. This work provides a feasible way for the rapid production of metal phosphides for energy conversion and storage applications.

15.
J Chem Phys ; 159(13)2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37787139

RESUMEN

Developing bifunctional catalysts for overall water splitting with high activity and durability at high current density remains a challenge. In an attempt to overcome this bottleneck, in this work, unique CoNiFe-layered double hydroxide nanoflowers are in situ grown on nickel-iron (NiFe) foam through a corrosive approach and following a chemical vapor deposition process to generate nitrogen-doped carbon nanotubes at the presence of melamine (CoNiFe@NCNTs). The coupling effects between various metal species act a key role in accelerating the reaction kinetics. Moreover, the in situ formed NCNTs also favor promoting electrocatalytic activity and stability. For oxygen evolution reaction it requires low overpotentials of 330 and 341 mV in 1M KOH and 1M KOH + seawater to drive 500 mA cm-2. Moreover, water electrolysis can be operated with CoNiFe@NCNTs as both anode and cathode with small voltages of 1.95 and 1.93 V to achieve 500 mA cm-2 in 1M KOH and 1M KOH + seawater, respectively.

16.
Sensors (Basel) ; 23(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37896707

RESUMEN

In the domain of optical fiber distributed acoustic sensing, the persistent challenge of extending sensing distances while concurrently improving spatial resolution and frequency response range has been a complex endeavor. The amalgamation of pulse compression and frequency division multiplexing methodologies has provided certain advantages. Nevertheless, this approach is accompanied by the drawback of significant bandwidth utilization and amplified hardware investments. This study introduces an innovative distributed optical fiber acoustic sensing system aimed at optimizing the efficient utilization of spectral resources by combining compressed pulses and frequency division multiplexing. The system continuously injects non-linear frequency modulation detection pulses spanning various frequency ranges. The incorporation of non-uniform frequency division multiplexing augments the vibration frequency response spectrum. Additionally, nonlinear frequency modulation adeptly reduces crosstalk and enhances sidelobe suppression, all while maintaining a favorable signal-to-noise ratio. Consequently, this methodology substantially advances the spatial resolution of the sensing system. Experimental validation encompassed the multiplexing of eight frequencies within a 120 MHz bandwidth. The results illustrate a spatial resolution of approximately 5 m and an expanded frequency response range extending from 1 to 20 kHz across a 16.3 km optical fiber. This achievement not only enhances spectral resource utilization but also reduces hardware costs, making the system even more suitable for practical engineering applications.

17.
Mol Cancer ; 21(1): 2, 2022 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-34980132

RESUMEN

BACKGROUND: In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them. METHODS: In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses. RESULTS: We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined. CONCLUSION: Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.


Asunto(s)
Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Pruebas Genéticas/métodos , Genómica/métodos , Oncología Médica , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Toma de Decisiones Clínicas , Biología Computacional/métodos , Manejo de la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Oncología Médica/métodos , Oncología Médica/normas , Pronóstico , Transcriptoma , Resultado del Tratamiento
18.
Small ; 15(49): e1904663, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31631530

RESUMEN

Nickel/cobalt hydroxide is a promising battery-type electrode material for supercapacitors. However, its low cycle stability hinders further applications. Herein, Ni0.7 Co0.3 (OH)2 core-shell microspheres exhibiting extreme-prolonged cycling life are successfully synthesized, employing Ni-Co-metal-organic framework (MOF) as the precursor/template and a specific hydrolysis strategy. The Ni-Co-MOF and KOH aqueous solution are separated and heated to 120 °C before mixing, rather than mixing before heating. Through this hydrolysis strategy, no MOF residual exists in the product, contributing to close stacking of the hydroxide nanoflakes to generate Ni0.7 Co0.3 (OH)2 microspheres with a robust core-shell structure. The electrode material exhibits high specific capacity (945 C g-1 at 0.5 A g-1 ) and unprecedented cycling performance (100% after 10 000 cycles). The fabricated asymmetric supercapacitor delivers an energy density of 40.14 Wh kg-1 at a power density of 400.56 W kg-1 and excellent cycling stability (100% after 20 000 cycles). As far as is known, it is the best cycling performance for pure Ni/Co(OH)2 .

19.
Chemistry ; 24(9): 2137-2143, 2018 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-29064590

RESUMEN

A barium(II) metal-organic framework (MOF) based on a predesigned amino-functionalized ligand, namely [Ba2 (L)(DMF)(H2 O)(NO3 )1/3 ]⋅DMF⋅EtOH⋅2 H2 O (UPC-33) [H3 L=4,4'-((2-amino-5-carboxy-1,3-phenylene)bis(ethyne-2,1-diyl))dibenzoic acid] has been synthesized. UPC-33 is a 3-dimensional 3,18-connected network with fcu topology with a rare twelve-nuclear Ba12 (COO)18 (NO3 )2 cluster. UPC-33 shows permanent porosity and a high adsorption heat of CO2 (49.92 kJ mol-1 ), which can be used as a platform for selective adsorption of CO2 /CH4 (8.09). In addition, UPC-33 exhibits high separation selectivity for C3 light hydrocarbons with respect to CH4 (228.34, 151.40 for C3 H6 /CH4 , C3 H8 /CH4 at 273k and 1 bar), as shown by single component gas sorption and selectivity calculations. Due to the existence of -NH2 groups in the channels, UPC-33 can effectively catalyze Knoevenagel condensation reactions with high yield, and substrate size and electron dependency.

20.
Inorg Chem ; 57(17): 10953-10960, 2018 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-30137967

RESUMEN

Supercapacitors are regarded to be highly probable candidates for next-generation energy storage devices. Herein, a bimetallic Co/Ni MOF is used as a sacrificial template through an alkaline hydrolysis and selective oxidation process to prepare an accordion-like ternary NiCo2O4/ß-Ni xCo1- x(OH)2/α-Ni xCo1- x(OH)2 composite, which is composed of Co/Ni(OH)2 nanosheets with large specific surface as the frame and NiCo2O4 nanoparticles with high conductivity as the insertion, for supercapacitor application. This material exhibits both high specific capacitance (1315 F·g-1 at 5 A·g-1) and excellent cycle performance (retained 90.7% after 10 000 cycles). This hydrolysis-oxidation process, alkali hydrolysis followed by oxidation with H2O2, offers a novel approach to fabricate the Ni/Co-based electrode materials with enhanced supercapacitor performance.

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