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Aqueous aluminum ion batteries (AAIBs) hold significant potential for grid-scale energy storage owing to their intrinsic safety, high theoretical capacity, and abundance of aluminum. However, the strong electrostatic interactions and delayed charge compensation between high-charge-density aluminum ions and the fixed lattice in conventional cathodes impede the development of high-performance AAIBs. To address this issue, this work introduces, for the first time, high-entropy Prussian blue analogs (HEPBAs) as cathodes in AAIBs with unique lattice tolerance and efficient multipath electron transfer. Benefiting from the intrinsic long-range disorder and robust lattice strain field, HEPBAs enable the manifestation of the lattice respiration effect and minimize lattice volume changes, thereby achieving one of the best long-term stabilities (91.2% capacity retention after 10 000 cycles at 5.0 A g-1) in AAIBs. Additionally, the interaction between the diverse metal atoms generates a broadened d-band and reduced degeneracy compared with conventional Prussian blue and its analogs (PBAs), which enhances the electron transfer efficiency with one of the best rate performance (79.2 mAh g-1 at 5.0 A g-1) in AAIBs. Furthermore, exceptional element selectivity in HEPBAs with unique cocktail effect can facile tune electrochemical behavior. Overall, the newly developed HEPBAs with a high-entropy effect exhibit promising solutions for advancing AAIBs and multivalent-ion batteries.
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PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.
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A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.
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Sistemas de Liberación de Medicamentos , Endosomas , Preparaciones Farmacéuticas , Endosomas/metabolismo , Péptidos/metabolismo , Concentración de Iones de HidrógenoRESUMEN
Rechargeable aqueous aluminum batteries (AABs) are promising energy storage technologies owing to their high safety and ultra-high energy-to-price ratio. However, either the strong electrostatic forces between high-charge-density Al3+ and host lattice, or sluggish large carrier-ion diffusion toward the conventional inorganic cathodes generates inferior cycling stability and low rate-capacity. To overcome these inherent confinements, a series of promising redox-active organic materials (ROMs) are investigated and a π-conjugated structure ROMs with synergistic CâO and CâN groups is optimized as the new cathode in AABs. Benefiting from the joint utilization of multi-redox centers and rich π-π intermolecular interactions, the optimized ROMs with unique ion coordination storage mechanism facilely accommodate complex active ions with mitigated coulombic repulsion and robust lattice structure, which is further validated via theoretical simulations. Thus, the cathode achieves enhanced rate performance (153.9 mAh g-1 at 2.0 A g-1) and one of the best long-term stabilities (125.7 mAh g-1 after 4,000 cycles at 1.0 A g-1) in AABs. Via molecular exploitation, this work paves the new direction toward high-performance cathode materials in aqueous multivalent-ion battery systems.
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The strong electrostatic interaction between high-charge-density zinc ions (112 C mm-3 ) and the fixed crystallinity of traditional oxide cathodes with delayed charge compensation hinders the development of high-performance aqueous zinc-ion batteries (AZIBs). Herein, to intrinsically promote electron transfer efficiency and improve lattice tolerance, a revolutionary family of high-entropy oxides (HEOs) materials with multipath electron transfer and remarkable structural stability as cathodes for AZIBs is proposed. Benefiting from the unique "cock-tail" effect, the interaction of diverse type metal-atoms in HEOs achieves essentially broadened d-band and lower degeneracy than monometallic oxides, which contribute to convenient electron transfer and one of the best rate-performances (136.2 mAh g-1 at 10.0 A g-1 ) in AZIBs. In addition, the intense lattice strain field of HEOs is highly tolerant to the electrostatic repulsion of high-charge-density Zn2+ , leading to the outstanding cycling stability in AZIBs. Moreover, the super selectability of elements in HEOs exhibits significant potential for AZIBs.
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The tumor microenvironment is a very complex and dynamic ecosystem. Although a variety of pH-responsive peptides have been reported to deliver nucleic acid drugs for cancer treatment, these responses typically only target the acidic microenvironment of the tumor or the lysosome, and the carrier suffers from issues such as low transfection efficiency and poor lysosomal escape within the cell. To address this problem, we have developed an ultra pH-responsive peptide nanocarrier that can efficiently deliver siRNA, pDNA, and mRNA into cancer cells by performing progressive dynamic assembly in response to pH changes in the acidic tumor microenvironment (pH 6.5-6.8) and the acidic intracellular lysosomal environment (pH 5.0-6.0). The maximum transfection efficiency was 87.1% for pDNA and 74.9% for mRNA, which is higher than that of peptide-based nanocarrier reported to date. In addition, the targeting sequence on the surface allows the peptide@siRNA complex to efficiently enter cancer cells, causing 96% of cancer cell mortality. The carrier has high biocompatibility and low cytotoxicity, making it highly promising for application in immunotherapy and gene therapy of tumors.
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Neoplasias , Microambiente Tumoral , Genes Relacionados con las Neoplasias , Concentración de Iones de Hidrógeno , Neoplasias/tratamiento farmacológico , Péptidos , ARN Mensajero , ARN Interferente Pequeño/farmacologíaRESUMEN
AIM: To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. METHOD: A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. RESULTS: The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p < 0.01). INTERPRETATION: Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. WHAT THIS PAPER ADDS: The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.
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Toxinas Botulínicas Tipo A , Parálisis Cerebral , Niño , Masculino , Femenino , Humanos , Lactante , Preescolar , Estudios Retrospectivos , Inyecciones , Incidencia , Índice de Severidad de la EnfermedadRESUMEN
Rechargeable aluminum batteries (RABs), with abundant aluminum reserves, low cost, and high safety, give them outstanding advantages in the postlithium batteries era. However, the high charge density (364 C mm-3 ) and large binding energy of three-electron-charge aluminum ions (Al3+ ) de-intercalation usually lead to irreversible structural deterioration and decayed battery performance. Herein, to mitigate these inherent defects from Al3+ , an unexplored family of superlattice-type tungsten selenide-sodium dodecylbenzene sulfonate (SDBS) (S-WSe2 ) cathode in RABs with a stably crystal structure, expanded interlayer, and enhanced Al-ion diffusion kinetic process is proposed. Benefiting from the unique advantage of superlattice-type structure, the anionic surfactant SDBS in S-WSe2 can effectively tune the interlayer spacing of WSe2 with released crystal strain from high-charge-density Al3+ and achieve impressively long-term cycle stability (110 mAh g-1 over 1500 cycles at 2.0 A g-1 ). Meanwhile, the optimized S-WSe2 cathode with intrinsic negative attraction of SDBS significantly accelerates the Al3+ diffusion process with one of the best rate performances (165 mAh g-1 at 2.0 A g-1 ) in RABs. The findings of this study pave a new direction toward durable and high-performance electrode materials for RABs.
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This study aimed to evaluate the effects of super-chilled storage (-1.3 °C) combined with starch film packaging containing different contents of sea buckthorn pomace extract (SSF, 0, 1, 2, and 3%, w/w) on the quality of chilled beef. The release kinetics, microstructure, and mechanical properties of the film were also measured to investigate its suitability for super-chilled storage. The results of the meat quality assessment showed that the L*, a*, and sensory evaluation values of the SSF-3% samples were significantly higher (P < 0.05), and the pH, b*, thiobarbituric acid reactive substance (TBARS), total volatile basic nitrogen (TVB-N), and total viable count (TCA) were significantly lower (P < 0.05) than the SSF-0%. The release of SBP from the SSF film was controlled by diffusion. Furthermore, SSF-3% was found to have a compact microstructure and good mechanical properties at the end of the super-chilled storage. The results demonstrated that SSF is an effective packaging material for beef at super-chilling temperatures.
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Embalaje de Alimentos/métodos , Extractos Vegetales , Carne Roja/análisis , Animales , Carga Bacteriana , Bovinos , Microbiología de Alimentos , Almacenamiento de Alimentos/métodos , Hippophae/química , Masculino , Nitrógeno/análisis , Carne Roja/microbiología , Almidón , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
This study investigated the effect of lysosomal iron involvement in the mechanism of mitochondrial apoptosis on bovine muscle protein degradation during postmortem aging. Six crossbred cattle were studied to evaluate intracellular reactive oxygen species (ROS), antioxidant enzyme activity, lysosomal membrane stability, mitochondrial dysfunction-induced apoptosis, desmin and troponin-T degradation in both control and iron chelator desferrioxamine (DFO) groups. Results showed that lysosomal iron induced ROS accumulation and lysosomal membrane destabilization by decreasing the antioxidant enzyme activity (P < 0.05). Subsequently, lysosomal dysfunction mediated by iron increased mitochondrial membrane permeability and decreased mitochondrial membrane potential, thereby enhancing Bid and cytochrome c release and caspase-9/-3 activation (P < 0.05). Ultimately, lysosomal iron mediated lysosomal-mitochondrial apoptosis increased the postmortem bovine muscle desmin and troponin-T degradation (P < 0.05). The results indicated that lysosomal iron contributes to postmortem meat tenderization through the lysosomal-mitochondrial dysfunction-induced apoptosis pathway.
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Hierro/metabolismo , Lisosomas/metabolismo , Proteínas de la Carne/metabolismo , Mitocondrias Musculares/patología , Membranas Mitocondriales/patología , Animales , Apoptosis/efectos de los fármacos , Autopsia , Bovinos , Permeabilidad de la Membrana Celular , Citocromos c/metabolismo , Masculino , Mitocondrias/metabolismo , Mitocondrias Musculares/metabolismo , Membranas Mitocondriales/metabolismo , Proteínas Musculares/metabolismo , Proteolisis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study investigated the activity of adenosine monophosphate-activated protein kinase (AMPK), glycolysis, and meat quality index in three altitude bovines during postmortem aging process. Local cattle (altitude:1,500 m), Gannan yak (3,000 m), and Yushu yak (4,500 m) postmortem Longissimus Dorsi (LD) muscle were used. Results indicated that CaCl2 significantly increased the AMPK activity by increasing the calcium-regulated protein kinase kinase (CaMKKß) activity. Besides, AMPK activation enhanced the activity of lactate dehydrogenase (LDH) and Ca2+ -ATPase and accelerated the rate of muscle maturation during postmortem aging. Moreover, the expression of HIF-1, PRKAA2, and GLUT4 genes in high-altitude Yushu yak was higher than that of low-altitude bovines. CaCl2 activates AMPK by activating CaMKKß cascade and accelerates postmortem glycolysis affecting the intramuscular environment, color, and muscle protein degradation to accelerate postmortem muscle maturation, suggesting that AMPK has essential effects on postmortem muscle glycolysis and quality, and can regulate muscle quality by regulating postmortem muscle AMPK activity. PRACTICAL APPLICATIONS: Insufficient postmortem glycolysis usually leads to DFD (dark, firm, and dry) meat. Beef have relatively high incidences of DFD meat, which has an unattractive dark color and causes significant loss to the meat industry. Therefore, AMPK, which can regulate postmortem glycolysis to affect meat quality, is a valid research target.
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Bovinos/metabolismo , Carne/análisis , Músculo Esquelético/metabolismo , Adenosina Monofosfato/metabolismo , Altitud , Animales , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Bovinos/genética , Glucólisis , Músculo Esquelético/química , Fosforilación , Control de CalidadRESUMEN
This study investigated the apoptosis pathway mediated by apoptosis-inducing factors (AIF) and internal factors that influence the release of AIF. The results indicated that the AIF expression was decreased in mitochondria and increased in nucleus (Pâ¯<â¯0.05). However, no significant differences were observed in the AIF expression in mitochondria with caspase inhibitor treatment. The optical density of nucleus and mitochondrial swelling was significant increased (Pâ¯<â¯0.05). Reactive oxygen species (ROS) fell gradually within the first 6â¯h and increased in the next 24â¯h. Calpain I activity was decreased, Ca2+ concentration, cathepsin B and D activities was increased (Pâ¯<â¯0.05). The results demonstrated that AIF-mediated caspase-dependent pathway was a new mitochondrial apoptosis pathway and that mitochondrial swelling, ROS content, Ca2+ concentration, calpain I, cathepsin B and cathepsin D activities are the key influencing factors in apoptosis in postmortem bovine muscle.
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Envejecimiento/metabolismo , Factor Inductor de la Apoptosis/metabolismo , Apoptosis , Músculos/citología , Músculos/metabolismo , Animales , Bovinos , Humanos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The objective of this study was to investigate the effects of modified atmosphere packaging (MAP) systems on shelf-life and quality of beef steaks with high marbling. Four packaging types were used including 80% O2 MAP (80% O2+20% CO2), 50% O2 MAP (50% O2+30% CO2+20% N2), carbon monoxide MAP (0.4% CO+30% CO2+69.6% N2) and vacuum packaging (VP). Steaks were displayed under simulated retail conditions at 4°C for 12days. Purge loss, pH, color stability, oxidative stability and microbial counts were monitored. Aerobically packaged steaks exhibited a bright-red color at the first 4days. However, discoloration and oxidation became major factors limiting their shelf-life to 8days. Compared with aerobic packaging, anaerobic packaging extended shelf-life of heavily marbled beef steaks, due to better color stability, together with lower oxidation and microbial populations. Among all packaging methods, CO-MAP had the best preservation for steaks, with more red color than other packaging types.