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1.
Fish Shellfish Immunol ; 151: 109690, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866347

RESUMEN

Leucine is an essential amino acid for fish. The ability of leucine to resist stress in fish has not been reported. Nitrite is a common pollutant in the aquatic environment. Therefore, we investigated the effects of dietary leucine on growth performance and nitrite-induced liver damage, mitochondrial dysfunction, autophagy, and apoptosis for sub-adult grass carp. A total of 450 grass carp (615.91 ± 1.15 g) were selected and randomly placed into 18 net cages. The leucine contents of the six diets were 2.91, 5.90, 8.92, 11.91, 14.93, and 17.92 g/kg, respectively. After a 9-week feeding trial, the nitrite exposure experiment was set up for 96 h. These results indicated that dietary leucine significantly promoted FW, WG, PWG, and SGR of sub-adult grass carp (P < 0.05). Appropriate levels of dietary leucine (11.91-17.92 g/kg) decreased the activities of serum parameters (glucose, cortisol, and methemoglobin contents, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase), the contents of reactive oxygen species (ROS), nitric oxide (NO) and peroxynitrite (ONOO-). In addition, appropriate levels of dietary leucine (11.91-17.92 g/kg) increased the mRNA levels of mitochondrial biogenesis genes (PGC-1α, Nrf1/2, TFAM), fusion-related genes (Opa1, Mfn1/2) (P < 0.05), and decreased the mRNA levels of caspase 3, caspase 8, caspase 9, fission-related gene (Drp1), mitophagy-related genes (Pink1, Parkin) and autophagy-related genes (Beclin1, Ulk1, Atg5, Atg7, Atg12) (P < 0.05). Appropriate levels of dietary leucine (8.92-17.92 g/kg) also increased the protein levels of AMP-activated protein kinase (AMPK), prostacyclin (p62) and decreased the protein levels of protein light chain 3 (LC3), E3 ubiquitin ligase (Parkin), and Cytochrome c (Cytc). Appropriate levels of leucine (8.92-17.92 g/kg) could promote growth performance and alleviate nitrite-induced mitochondrial dysfunction, autophagy, apoptosis for sub-adult grass carp. Based on quadratic regression analysis of PWG and serum GPT activity, dietary leucine requirements of sub-adult grass carp were recommended to be 12.47 g/kg diet and 12.55 g/kg diet, respectively.

2.
Int Orthop ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38679689

RESUMEN

PURPOSE: We retrospectively evaluated the characteristics of these patients and the effectiveness of ankle arthrodesis in the treatment of ankle arthritis caused by Kashin-Beck disease (KBD). METHODS: A retrospective study of KBD patients with ankle osteoarthritis who underwent ankle arthrodesis between December 2012 and January 2022 was performed. A total of 46 patients were included. The general characteristics, clinical manifestations and imaging features of the patients were recorded and summarized. measured using the VAS score, and ankle function was assessed by the AOFAS ankle-hindfoot score. RESULTS: Multiple subchondral cystic changes were found in 42(91.3%) patients. The VAS scores for both resting and weight-bearing conditions were 6.28 ± 1.30 vs. 2.09 ± 1.12 (P < .001) and 6.87 ± 1.01 vs. 2.17 ± 0.98 (P < .001), respectively. The AOFAS scores were 59.17 ± 5.50 and 88.39 ± 1.42, respectively (P < .001). CONCLUSIONS: The subchondral multiple cystic transformation of the ankle KBD has a certain suggestive role.Arthrodesis is an effective method to reduce ankle pain and improve ankle function in KBD patients with ankle osteoarthritis.

3.
Org Lett ; 26(18): 3739-3743, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38679883

RESUMEN

An enantioselective Pd-catalyzed intramolecular dearomative reductive Heck reaction of N-(o-bromoaryl) indole-3-carboxamide is developed. By employing Pd(dba)2/SPINOL-based phosphoramidite as the chiral catalyst and HCO2Na as the hydride source, a series of enantioenriched spiro indolines bearing vicinal stereocenters were afforded in moderate to good yields with excellent enantioselectivities. The reductive Heck reaction of formal tetrasubstituted alkene bearing ß-hydrogens is therefore realized by inhibiting ß-H elimination.

4.
Chem Commun (Camb) ; 60(28): 3858-3861, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38497365

RESUMEN

Herein, we describe a copper-catalyzed intramolecular dearomative amination of indoles via a formal aza-Wacker reaction. This protocol provides an efficient method to access aza-polycyclic indoline molecules bearing exocyclic CC bonds in moderate to excellent yields in the presence of molecular oxygen as an oxidant. It is worth noting that indolin-3-ones are achieved when employing C3-non-substituted indoles as substrates.

5.
Hortic Res ; 11(3): uhae016, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38495032

RESUMEN

Artificially enhancing photosynthesis is critical for improving crop yields and fruit qualities. Nanomaterials have demonstrated great potential to enhance photosynthetic efficiency; however, the mechanisms underlying their effects are poorly understood. This study revealed that the electron transfer pathway participated in nitrogen-doped carbon dots (N-CDs)-induced photosynthetic efficiency enhancement (24.29%), resulting in the improvements of apple fruit qualities (soluble sugar content: 11.43%) in the orchard. We also found that N-CDs alleviated mterf5 mutant-modulated photosystem II (PSII) defects, but not psa3 mutant-modulated photosystem I (PSI) defects, suggesting that the N-CDs-targeting sites were located between PSII and PSI. Measurements of chlorophyll fluorescence parameters suggested that plastoquinone (PQ), the mobile electron carrier in the photosynthesis electron transfer chain (PETC), was the photosynthesis component that N-CDs targeted. In vitro experiments demonstrated that plastoquinone-9 (PQ-9) could accept electrons from light-excited N-CDs to produce the reduced plastoquinone 9 (PQH2-9). These findings suggested that N-CDs, as electron donors, offer a PQ-9-involved complement of PETC to improve photosynthesis and thereby fruit quality. Our study uncovered a mechanism by which nanomaterials enhanced plant photosynthesis and provided some insights that will be useful in the design of efficient nanomaterials for agricultural/horticultural applications.

6.
Plant Cell Environ ; 47(5): 1668-1684, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38282271

RESUMEN

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.


Asunto(s)
Sequías , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regiones Promotoras Genéticas , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética
7.
J Fish Biol ; 104(2): 463-472, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36808734

RESUMEN

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.


Asunto(s)
Salmonidae , Contaminantes Químicos del Agua , Animales , Cobre/toxicidad , Larva , Zinc/toxicidad , Acuicultura , Contaminantes Químicos del Agua/toxicidad , Embrión no Mamífero
8.
Aging (Albany NY) ; 15(16): 8433-8443, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37647020

RESUMEN

Adult hippocampal neurogenesis provides a regenerative resource for neural tissue and enhances neural plasticity, which is beneficial for brain functional rehabilitation post stroke. Recently, an increasing number of metabolic drugs have been reported to attenuate behavioral symptoms in neurodegeneration or psychiatric disorders via promoting adult hippocampal neurogenesis. Bioeffects of catapol show its potential as an antidiabetic though it has been previously widely indicated to perform the neuroprotective functions. However, the systematic evidence to support the behavioral effects of catapol to PSD model and what is the role of adult neurogenesis in such effects remains unexplored. In current study, we created the PSD model by combining MCAO procedure and CORT feeding. The treatment of catapol strikingly reduced the depressive/anxiety behavior in PSD model. Moreover, treatment of catapol also improved the cognitive functions. Immunofluorescence indicates that catapol could promote adult hippocampal neurogenesis in PSD model, and TMZ treatment further confirmed the role of the hippocampal neurogenesis in catapol's therapeutic effects to PSD. Cultural neurons also indicates that PI3K is the key signal in regulating catapol mediated neurogenesis. By administrating the PI3K specific inhibitor, we found that PI3K is the key to mediate the behavioral effects of catapol to PSD. In conclusion, catapol could perform as the effective drug to treat PSD via the PI3K mediated adult hippocampal neurogenesis.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Accidente Cerebrovascular , Animales , Ratones , Depresión , Neurogénesis , Cognición , Inhibidores de las Quinasa Fosfoinosítidos-3
9.
J Clin Lab Anal ; 37(5): e24858, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36916770

RESUMEN

The most prevalent viruses currently causing diarrhea are norovirus and rotavirus, and rapid and sensitive detection methods are essential for the early diagnosis of disease. The purpose of this study was to establish a sensitive single-tube two-stage nucleic acid amplification method-reverse transcription recombinase-assisted PCR (RT-RAP)-for simultaneous detection of norovirus GII and group A Rotavirus, with the first stage consisting of isothermal reverse transcription recombinase-aided amplification (RT-RAA) and the second stage consisting of qPCR (quantitative PCR). RT-RAP is more sensitive than either RT-RAA or qRT-PCR (quantitative RT-PCR) alone. And the addition of a barrier that can be disassembled after heating enabled the detection of samples within 1 h in a single closed tube. Sensitivity was 10 copies/reaction of norovirus (Novs) GII and group A rotavirus (RVA). In parallel, two hundred fecal specimens were used to evaluate the method and compare it with a commercial fluorescent quantitative RT-PCR. The data showed kappa values of 0.957 and 0.98 (p < 0.05) for detecting Novs GII and RVA by the two methods, indicating the potential of the newly established assay to be applied to clinical and laboratory testing.


Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Rotavirus , Humanos , Rotavirus/genética , Norovirus/genética , Gastroenteritis/diagnóstico , Infecciones por Caliciviridae/diagnóstico , Heces , Recombinasas , Sensibilidad y Especificidad
10.
CNS Neurosci Ther ; 29(1): 168-180, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36217678

RESUMEN

AIMS: Efficiency of neural stem cells (NSCs) therapy for brain injury is restricted by astrogliosis around the damaged region, in which JAK2/STAT3 signaling plays a key role. The SOCS3 that can directly inhibit JAK/STAT3 pathway. Here, we investigated the effects of a fusion peptide that combined kinase inhibitory region (KIR) of SOCS3 and virus trans-activator of transcription (TAT) on biological behavior of cultured NSCs under inflammatory conditions. METHODS: NSCs were isolated from embryonic brain of SD rats, TAT-KIR was synthesized, and penetration rate was evaluated by flow cytometry (FACS). CCK8, immunostaining, and FACS were used to detected of TAT-KIR on the proliferation of NSCs. The expressions of GFAP and ß tubulin III positive cells induced by IL6 with/without TAT-KIR were examined by immunostaining and Western blotting to observe the NSCs differentiation, and the effect of TAT-KIR on signaling cross talk was observed by Western blotting. RESULTS: Penetration rate of TAT-KIR into primary cultured NSCs was up to 94%. TAT-KIR did not affect the growth and viability of NSCs. It significantly reduced the NSCs proliferation that enhanced by IL-6 stimulation via blocking the cell cycle progression from the G0/G1 to S phase. In addition, TAT-KIR attenuated astrocytic differentiation and kept high level of neuronal differentiation derived from IL-6-induced NSCs. The fate of NSCs differentiation under inflammatory conditions was affected by TAT-KIR, which was associated with synchronous inhibition of STAT3 and AKT, while promoting JNK expression. CONCLUSION: TAT-KIR mimetic of SOCS3 could be a promising approach for brain repair via regulating the biological behaviors of exogenous NSCs.


Asunto(s)
Interleucina-6 , Células-Madre Neurales , Animales , Ratas , Diferenciación Celular , Proliferación Celular , Interleucina-6/metabolismo , Células-Madre Neurales/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo
11.
Br J Neurosurg ; 37(5): 1371-1374, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32924632

RESUMEN

PURPOSE: Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine is usually progressive and responds poorly to conservative therapy, making surgery the only effective treatment option. A variety of surgical procedures have been developed to treat thoracic OPLL. However, the optimal surgical approach for removal of thoracic OPLL remains unclear. In the present study, we described a newly modified posterior approach for the removal of OPLL: circular decompression via dural approach, and complete removal of OPLL can be achieved under direct vision and without neurological deficit. MATERIALS AND METHODS: Three patients with beak-type thoracic OPLL presented with progressive thoracic myelopathy and leg weakness. Magnetic resonance imaging showed the spinal cord severely compressed. The surgical management of the three patients involved the 'cave-in' circular decompression and transdural resection of OPLL. RESULTS: Transdural circumferential decompression was successfully performed in all three patients. Clinical outcome measures, including pre- and postoperative radiographic parameters, were assessed. All of the patients were followed up for an average of 12 months (ranging from 10 to 15 months), and no surgery-related complications occurred. Weakness relief and neural function recovery were satisfactorily achieved in all patients by the final follow-up. CONCLUSIONS: Transdural circumferential decompression was an effective method for thoracic spinal stenosis caused by concurrent beak-type OPLL, by which OPLL could be safely removed. It is especially useful when there is a severe adhesion between the dura OPLL.


Asunto(s)
Osificación del Ligamento Longitudinal Posterior , Enfermedades de la Médula Espinal , Fusión Vertebral , Estenosis Espinal , Animales , Humanos , Ligamentos Longitudinales/cirugía , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/etiología , Estenosis Espinal/cirugía , Osteogénesis , Descompresión Quirúrgica/métodos , Pico/cirugía , Fusión Vertebral/métodos , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Osificación del Ligamento Longitudinal Posterior/complicaciones , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Osificación del Ligamento Longitudinal Posterior/cirugía , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/cirugía , Resultado del Tratamiento
13.
Proteins ; 91(1): 3-15, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36053994

RESUMEN

Despite differences in behaviors and living conditions, vertebrate organisms share the great majority of proteins, often with subtle differences in amino acid sequence. Here, we present a simple way to analyze the difference in amino acid occurrence by comparing highly homologous proteins on a subproteome level between several vertebrate model organisms. Specifically, we use this method to identify a pattern of amino acid conservation as well as a shift in amino acid occurrence between homeotherms (warm-blooded species) and poikilotherms (cold-blooded species). Importantly, this general analysis and a specific example further establish a broad correlation, if not likely connection between the thermal adaptation of protein sequences and two of their physical features: on average a change in their protein dynamics and, even more strongly, in their solvation. For poikilotherms, such as frog and fish, the lower body temperature is expected to increase the protein-protein interaction due to a decrease in protein internal dynamics. In order to counteract the tendency for enhanced binding caused by low temperatures, poikilotherms enhance the solvation of their proteins by favoring polar amino acids. This feature appears to dominate over possible changes in dynamics for some proteins. The results suggest that a general trend for amino acid choice is part of the mechanism for thermoadaptation of vertebrate organisms at the molecular level.


Asunto(s)
Proteoma , Vertebrados , Animales , Proteoma/metabolismo , Vertebrados/metabolismo , Secuencia de Aminoácidos , Frío , Aminoácidos/metabolismo
14.
Expert Syst Appl ; 214: 119145, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36339965

RESUMEN

During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.

15.
Chinese Journal of Biotechnology ; (12): 4335-4357, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1008029

RESUMEN

Biomanufacturing uses biological systems, including cells, microorganisms, and enzymes, to produce natural or synthetic molecules with biological activities for use in various industries, such as pharmaceuticals, cosmetics, and agriculture. These bioactive compounds are expected to play important roles in improving the quality of life and prolonging its length. Fortunately, recent advances in synthetic biology and automation technologies have accelerated the development of biomanufacturing, enabling us to create new products and replace conventional methods in a more sustainable manner. As of now, the role of biomanufacturing in the growth and innovation of bioeconomy is steadily increasing, and this techbology becomes a prevalent technology in global markets. To gain a comprehensive understanding of this field, this article presents a retrospective review of Bloomage Biotechnology's Research and Development and briefly reviews the developments of biomanufacturing and offers insights into the futre prospects. In conclusion, biomanufacturing will continue to be an important, environmentally friendly, and sustainable production mode in the ongoing development of bioeconomy.


Asunto(s)
Calidad de Vida , Biotecnología , Agricultura , Biología Sintética , Industrias
16.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1009852

RESUMEN

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.


Asunto(s)
Lactante , Recién Nacido , Humanos , Masculino , Lavado Broncoalveolar/efectos adversos , Proteinosis Alveolar Pulmonar/patología , Disnea/etiología , Insuficiencia Respiratoria
17.
Comput Struct Biotechnol J ; 20: 6078-6086, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36373151

RESUMEN

SARS-CoV-2 variants often include surface mutations in the Spike protein that are important for viruses to recognize host receptors and evade antibody neutralization. The Spike protein also has mutations in the interior of the protein likely to affect the Spike protein S1 - S2 subunit's separation propensity, the most important of which is the D614G mutation. Remarkably, the Omicron variant contains a large number of internal mutations at the S2: S1 interface, which have not been investigated yet. In this study, we examined the effects of such interfacial mutations on the S2: S1 and subunit domain interactions and on the subunit's dissociation process. We found that the interaction with S2 is mainly contributed by the three encapsulation domains, named INT, ED1 and ED2 of S1, which are sandwiched between the S1 RBD and N-terminal NTD domain. We found that D614 is the strongest contributor for the S2: S1 interaction which is greatly weakened by the D614G mutation. Surprisingly, we found that, mutations T547K, H655Y, N764K, N856K, N969K, L981F in the Omicron variant largely enhance the S2: ED1 interaction, partially compensating the loss of S2: ED2 interaction due to the D614G mutation. Lastly, these results, together with biological considerations, allow us to suggest that in addition to the binding strength of between the RBD and ACE2, the stability of the Spike protein and the propensity of Spike protein S2: S1 separation are critical factors which likely exist in a balance for a particular infectivity and pathogenicity of the virus.

18.
Pharmaceutics ; 14(8)2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-36015311

RESUMEN

As a malignant tumor, liver cancer is mainly treated with chemotherapy, while chemotherapeutic drugs, such as doxorubicin (DOX), may lead to toxicity, drug resistance and poor prognosis. The targeted delivery systems of combining natural products and chemotherapeutic drugs are useful to eliminate cancers with reduced toxicity and increased efficiency. In this study, a diosgenin-based liposome loaded with DOX (Dios-DOX-LP) was developed for synergistic treatment of liver cancer, in which Dios not only replaced cholesterol as the membrane regulator to keep stability of liposomes, but also became the chemotherapy adjuvant of DOX for synergistic treatment. Dios-DOX-LP was characterized by particle size (99.4 ± 6.2 nm), zeta potential (-33.3 ± 2.5 mV), and entrapment efficiency (DOX: 98.77 ± 2.04%, Dios: 87.75 ± 2.93%), which had a good stability and slow-release effect. Compared with commercial DOX liposome (CHOL-DOX-LP), Dios-DOX-LP had an improved anti-tumor effect in vitro and in vivo by inducing the apoptosis and inhibiting the proliferation of the tumor cell, which was 1.6 times better than CHOL-DOX-LP in cytotoxicity, and had 78% of the tumor inhibition rate on tumor-bearing nude mice. Dios-DOX-LP provided a novel idea to achieve synergistic tumor treatment using diosgenin as a liposome material.

19.
Anal Methods ; 14(22): 2147-2152, 2022 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-35611957

RESUMEN

It is of great necessity to exploit a real-time, highly selective and sensitive method for hypochlorite (ClO-) detection in both the environment and living systems because of the complex influence of ClO- on health. In this paper, based on the intramolecular charge transfer (ICT) effect, a NIR fluorescent probe (probe DAB) was designed for the accurate detection of ClO-, which produced a fluorescence response to ClO- with high selectivity and rapid response (within 1 min). The probe DAB could determine ClO- over the linear range of 0-80 µM with a low detection limit of 1.46 µM. And the sensing mechanism between the probe and ClO- was verified using HPLC and MS. To further prove its practicability, the probe was applied for detecting ClO- in actual water samples. In addition, owing to its good sensing properties and low cytotoxicity, probe DAB could be expediently applied to visualize ClO- in living cells and zebrafish, and it is expected to be a useful tool for investigating the detailed functions and mechanisms of ClO- in living systems.


Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Animales , Límite de Detección , Microscopía Fluorescente/métodos , Pez Cebra
20.
Structure ; 30(6): 909-916.e2, 2022 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-35381186

RESUMEN

Dynamic allostery emphasizes a role of entropy change manifested as a sole change in protein fluctuations without structural changes. This kind of entropy-driven effect remains largely understudied. The most significant examples involve protein-ligand interactions, leaving protein-protein interactions, which are critical in signaling and other cellular events, largely unexplored. Here we study an example of how protein-protein interaction (binding of Ras to the Ras binding domain [RBD] of the effector protein Raf) affects a subsequent protein association process (Ras dimerization) by quenching Ras internal motions through dynamic allostery. We also investigate the influence of point mutations or ambient temperature, respectively, on the protein dynamics and interaction of two other systems: in adenylate kinase (ADK) and in the EphA2 SAM:Ship2 SAM complex. Based on these examples, we postulate that there are different ways in which dynamic-change-driven protein interactions are manifested and that it is likely a general biological phenomenon.


Asunto(s)
Proteínas , Dimerización , Ligandos , Unión Proteica
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