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OBJECTIVES: To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom, and to determine its sequence and structure. METHODS: Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom, and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording. The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry; its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry; its structure was established based on iterative thread assembly refinement online analysis. RESULTS: A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8, and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSGDSRLKD-OH. Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell, with 1.0 µmol/L SsTx-P2 suppressing 95% current of Kv4.1 channel. Its structure showed that SsTx-P2 shared a conserved helical structure. CONCLUSIONS: The study has isolated a novel peptide SsTx-P2 from centipede venom, which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.
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Secuencia de Aminoácidos , Venenos de Artrópodos , Canales de Potasio Shal , Animales , Humanos , Venenos de Artrópodos/química , Venenos de Artrópodos/farmacología , Datos de Secuencia Molecular , Péptidos/farmacología , Péptidos/aislamiento & purificación , Péptidos/química , Bloqueadores de los Canales de Potasio/farmacología , Bloqueadores de los Canales de Potasio/aislamiento & purificación , Bloqueadores de los Canales de Potasio/química , Canales de Potasio Shal/antagonistas & inhibidores , Quilópodos/químicaRESUMEN
In the vertebrate brain, sensory experience plays a crucial role in shaping thalamocortical connections for visual processing. However, it is still not clear how visual experience influences tissue homeostasis and neurogenesis in the developing thalamus. Here, we reported that the majority of SOX2-positive cells in the thalamus are differentiated neurons that receive visual inputs as early as stage 47 Xenopus. Visual deprivation (VD) for 2 days shifts the neurogenic balance toward proliferation at the expense of differentiation, which is accompanied by a reduction in nuclear-accumulated ß-catenin in SOX2-positive neurons. The knockdown of ß-catenin decreases the expression of SOX2 and increases the number of progenitor cells. Coimmunoprecipitation studies reveal the evolutionary conservation of strong interactions between ß-catenin and SOX2. These findings indicate that ß-catenin interacts with SOX2 to maintain homeostatic neurogenesis during thalamus development.
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Evolución Biológica , beta Catenina , Animales , Homeostasis , Tálamo , Xenopus laevisRESUMEN
Decades of intensifying human activities have caused dramatic changes in land use and land cover (LULC) in the ecologically fragile areas of the Qinghai-Tibet Plateau, which have led to significant changes in ecosystem service value (ESV). Taking the ecologically fragile Sanjiangyuan region of the Qinghai-Tibet Plateau as the research object, we focused on understanding the impact of LULC changes on the Sanjiangyuan's landscape pattern and its corresponding ESV, which was combined with a Markov-Plus model to predict LULC changes in 2030. The results showed: (1) from 2000 to 2020, the LULC of Sanjiangyuan has changed to varying degrees, respectively. In the central and southern regions where animal husbandry is the mainstay activity, the area of grass land converted to bareland had expanded; (2) from 2000 to 2010, the total regional ESV increased sharply. However, the total amount of ESV decreased from 2010 to 2020; (3) the overall ESV in the study area was observed to be trending down and is expected to decrease by approximately 4.25 billion CNY by 2030; (4) the fragmentation and complexity of regional landscape patterns will negatively affect local ecosystem stability and biodiversity. Overall, there is a strong temporal and spatial correlation between LULC and ESV. This study will provide a reference for the local government to provide targeted and sustainable land management policies, thereby promoting the improvement of the Qinghai-Tibet Plateau regional ecology value.
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Conservación de los Recursos Naturales , Ecosistema , Humanos , Tibet , Ecología , Biodiversidad , ChinaRESUMEN
Microplastics (MPs) may interfere with the primary ecological processes of soil, which has become a growing global environmental issue. In terrestrial ecosystems, litter decomposition is the main process of nutrient cycling, particularly for carbon (C) and nitrogen (N). However, how microplastic pollution could alter wetland litter decomposition has barely been investigated. Therefore, a 100-day lab-scale litter decomposition experiment was conducted using Shengjin Lake wetland soil, which was treated with two types of MPs (polyethylene, PE and polyvinyl chloride, PVC) at three concentrations (0.1%, 0.5%, and 2.5%, w/w), to explore if and how MPs accumulation could affect wetland litter decomposition processes. According to our research, the PE and PVC greatly slowed the decomposition rate of wetland litter. Compared with control treatments, the addition of MPs decreased litter quality (high C:N), reduced litter decomposition-related soil enzyme activity, decreased the diversity of bacteria, and altered microbial community structure and potential functional gene abundance linked to litter decomposition. These findings revealed that MPs could affect the main process of C and N cycling in wetland ecosystems, providing important cues for further research on the wetland ecosystem function.
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Ecosistema , Humedales , Microplásticos , Plásticos , Suelo/química , Microbiología del SueloRESUMEN
Understanding the nonequilibrium transformation of nanocatalysts under reaction conditions is important because metastable atomic structures may be created during the process, which offers unique activities in reactions. Although reshaping of metal nanoparticles (NPs) under reaction conditions has been widely recognized, the dynamic reshaping process has been less studied at the atomic scale. Here, we develop an atomistic kinetic Monte Carlo model to simulate the complete reshaping process of Pt nanoparticles in a CO environment and reveal the in situ formation of atomic clusters on the NP surface, a new type of active site beyond conventional understanding, boosting the reactivities in the CO oxidation reaction. Interestingly, highly active peninsula and inactive island clusters both form on the (111) facets and interchange in varying states of dynamic equilibrium, which influences the catalytic activities significantly. This study provides new fundamental knowledge of nanocatalysis and new guidance for the rational design of nanocatalysts.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is emerging as one of the fastest-growing causes of liver-related deaths worldwide. It is necessary to find strategies to effectively prevent and treat NAFLD, as no definitive drug has been approved. Nobiletin (NOB) is the critical active ingredient of Chinese herbal medicines such as Citrus aurantium and Citri Reticulatae Pericarpium, which have anti-inflammatory, antioxidant, lipid regulating, and insulin resistance regulating effects. Numerous studies have demonstrated that NOB can prevent and treat the onset and progression of NAFLD. In this review, the mechanisms of NOB for treating NAFLD have been summarized, hoping to provide a basis for subsequent studies of NOB and to provide a research ground for the development of therapeutic drugs for NAFLD.
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Medicamentos Herbarios Chinos , Flavonas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Flavonas/farmacología , Flavonas/uso terapéutico , Hígado , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Manufacturing of copper micro-patterns is crucial in electronics for its utilization as high conductivity transparent conductive films (TCFs) and circuits. In the preparation process of current TCFs, a plethora of materials have emerged that can replace traditional indium tin oxide (ITO). However, even for the most promising metal-based nanowire materials, there are issues such as high cost, complex welding, and high contact resistance. To address these problems, this paper proposes a printable and filament-drawable polydimethylsiloxane (PDMS)-based adhesive, which, through a novel additive patterning technology, efficiently and economically manufactures self-welding copper micro-meshes and circuits. The adhesive can be processed into micro-patterns through printing and filament drawing, on which ionic Ag can be in situ reduced and anchored, thereby eliminating the need for tedious pre- and post-treatment steps. The fully exposed Ag particles dramatically minimize the usage of precious metal catalyst, thus efficiently catalyzing electroless copper deposition (ECD) reaction. Highly conductive (1.03 × 107 S m-1) copper circuits can be fabricated on the printed adhesive patterns, exhibiting versatile applicability to diverse substrates. Highly precise copper micro-meshes (â¼50 µm) can be fabricated on the filament networks drawn by the adhesive. The copper meshes undergo complete self-welding at junctions during the ECD process, thus exhibiting ultra-low square resistance of 0.45 Ω sq-1 while maintaining a high transmittance of 82.2 %. This is far superior to most of TCFs in published literature.
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The catalytic activity of metal nanoparticles (NPs) is highly dependent on the coordination environment of the surface sites. Understanding the role of different sites in reactions is essential for gaining insights into catalytic activity and the precise design of catalysts. Herein, we used first-principles calculation-based kinetic Monte Carlo simulations to investigate correlations between different sites on Pt NPs in CO oxidation reactions. Low-coordinated (LC) sites favor the CO adsorption and reaction, whereas the oxygen mainly adsorbs on high-coordinated (HC) sites and diffuses to LC sites for reaction at low temperatures. Compared with step-dominated and terrace-dominated structures, the step-terrace structures exhibit higher activities. This reveals that the catalytic performance is not simply determined by the sites where the reaction occurs but is dramatically affected by the kinetic synergies between different sites. A proper way to optimize the activity of Pt catalysts is to balance the LC and HC sites.
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BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated demyelinating disease of the central nervous system (CNS). There is a lack of reports of sick sinus syndrome (SSS) associated with NMOSD; thus, we hereby report two cases of patients with NMOSD who developed SSS. CASES PRESENTATION: The patients were both male and presented with area postrema syndrome. Brain MRI showed lesions in the dorsal part of their medulla oblongata. They were diagnosed with NMOSD when aquaporin-4 antibodies were found in their serum. Slow heart rates and several episodes of syncope were also observed in case 1 during hospitalization, while Holter monitoring showed sinus pauses (10-11 s) and SSS was diagnosed. A pacemaker was fitted. Case 2 had a respiratory arrest followed by a subsequent cardiac arrest. He was successfully resuscitated with epinephrine injection and cardiopulmonary resuscitation. Through immunotherapy, their neurological functions became stable and heart rate and blood pressure returned to the baseline. CONCLUSIONS: Since sick sinus syndrome is a life-threatening complication, serious heart arrhythmias should be considered as a potential result of area postrema syndrome associated with NMOSD.
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Objective: The Omicron BA.5.2 variant of SARS-CoV-2 has undergone several evolutionary adaptations, leading to multiple subvariants. Rapid and accurate characterization of these subvariants is essential for effective treatment, particularly in critically ill patients. This study leverages Next-Generation Sequencing (NGS) to elucidate the clinical and immunological features across different Omicron BA.5.2 subvariants. Methods: We enrolled 28 patients infected with the Omicron variant, hospitalized in Zhangjiajie People's Hospital, Hunan, China, between January 20, 2023, and March 31, 2023. Throat swabs were collected upon admission for NGS-based identification of Omicron subvariants. Clinical data, including qSOFA scores and key laboratory tests, were collated. A detailed analysis of lymphocyte subsets was conducted to ascertain the extent of immune cell damage and disease severity. Results: Patients were infected with various Omicron subvariants, including BA.5.2.48, BA.5.2.49, BA.5.2.6, BF.7.14, DY.1, DY.2, DY.3, and DY.4. Despite having 43 identical mutation sites, each subvariant exhibited unique marker mutations. Critically ill patients demonstrated significant depletion in total lymphocyte count, T cells, CD4, CD8, B cells, and NK cells (P < 0.05). However, there were no significant differences in clinical and immunological markers across the subvariants. Conclusion: This study reveals that critically ill patients infected with different Omicron BA.5.2 subvariants experience similar levels of cellular immune dysfunction and inflammatory response. Four mutations - ORF1a:K3353R, ORF1a:L3667F, ORF1b:S997P, S:T883I showed correlation with immunological responses although this conclusion suffers from the small sample size. Our findings underscore the utility of NGS in the comprehensive assessment of infectious diseases, contributing to more effective clinical decision-making.
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COVID-19 , SARS-CoV-2 , Humanos , Enfermedad Crítica , Pueblos del Este de Asia , Secuenciación de Nucleótidos de Alto Rendimiento , SARS-CoV-2/genética , COVID-19/inmunología , COVID-19/virologíaRESUMEN
The morphology of nanoparticles (NPs) is crucial for determining their catalytic performance. The dramatic changes in the morphology of metal NPs during reactions observed in many in situ experiments pose great challenges for the identification of the geometry for optimal catalytic activities, which arouses the controversial understanding of the reaction mechanism. In this work, taking CO oxidation as a model reaction, we coupled a multiscale structure reconstruction model with kinetic Monte Carlo simulations to study the catalytic performance of the Pt NPs with changing morphology and reaction conditions. Through the quantitative analysis of contour plots for turnover frequencies, we show that the NPs with more well-coordinated sites exhibit optimal activity under CO-rich conditions at higher temperatures, while the reactivity of NPs with more low-coordination sites is optimal under O2-rich conditions at lower temperatures. Further analysis indicates that the competitive adsorption of CO and O2 plays the key role, in which the structure with optimal activity has a closer CO and O coverage. This work not only reconciles the controversy of the active geometry in the experiments, but offers an efficient method to guide the rational design of high-performance catalysts.
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BACKGROUND: Enteromorpha prolifera (E. prolifera) polysaccharide has become a promising feed additive with a variety of physiological activities, such as anti-oxidant, anti-cancer, anti-diabetic, immunomodulatory, hypolipidemic, and cation chelating ability. However, whether Enteromorpha polysaccharide-trace element complex supplementation regulates amino acid and fatty acid metabolism in chicken is largely unknown. This study was conducted to investigate the effects of E. prolifera polysaccharide (EP)-Zn supplementation on growth performance, amino acid, and fatty acid metabolism in chicken. METHODS: A total of 184 one-day-old Ross-308 broiler chickens were randomly divided into two treatment groups with 8 replicates, 12 chickens per replicate, and fed either the basal diet (control group) or basal diet plus E. prolifera polysaccharide-Zinc (400 mg EP-Zn/kg diet). RESULTS: Dietary EP-Zn supplementation significantly increased (P < 0.05) the body weight, average daily gain, muscle antioxidant activity, serum HDL level, and reduced serum TG and LDL concentration. In addition, dietary EP-Zn supplementation could modulate ileal amino acid digestibility and upregulate the mRNA expression of amino acid transporter genes in the jejunum, ileum, breast muscle, and liver tissues (P < 0.05). Compared with the control group, breast meat from chickens fed EP-Zn had higher (P < 0.05) Pro and Asp content, and lower (P < 0.05) Val, Phe, Gly, and Cys free amino acid content. Furthermore, EP-Zn supplementation upregulated (P < 0.05) the mRNA expressions of mTOR and anti-oxidant related genes, while down-regulated protein degradation related genes in the breast muscle. Breast meat from EP-Zn supplemented group had significantly lower (P < 0.05) proportions of Σn-3 PUFA, and a higher percentage of Σn-6 PUFA and the ratio of n-6/n-3 PUFA. Besides, EP-Zn supplementation regulated lipid metabolism by inhibiting the gene expression of key enzymes involved in the fatty acid synthesis and activating genes that participated in fatty acid oxidation in the liver tissue. CONCLUSIONS: It is concluded that EP-Zn complex supplementation regulates apparent ileal amino acid digestibility, enhances amino acid metabolism, and decreases oxidative stress-associated protein breakdown, thereby improving the growth performance. Furthermore, it promotes fatty acid oxidation and restrains fat synthesis through modulating lipid metabolism-related gene expression.
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Enteromorpha prolifera polysaccharide-zinc (EP-Zn), a kind of polysaccharide-zinc complex, has been shown to improve the immune response and reduce the inflammatory factors in weaned piglets. Yet, the molecular mechanism remains unclear. The present study was conducted to investigate the immunomodulating activity and anti-inflammatory mechanism of EP-Zn in mice. Different doses (350 mg kg-1, 700 mg kg-1, 1050 mg kg-1 and 1400 mg kg-1) of EP-Zn were administered to C57BL/6J mice for 28 days. The results showed that under physiological conditions, 350 mg kg-1 EP-Zn stimulated cytokine (TNF-α, IL-1ß, IL-6 and IL-10) secrection, regulated the intestinal microbiota, and reduced the levels of short-chain fatty acids (SCFAs) (acetic acid and propionic acid). In addition, in the LPS-induced inflammation model, EP-Zn pretreatment effectively alleviated LPS-induced shortening of colonic length and increased MPO and DAO contents, improved intestinal physical barrier function by modulating mucosal structure, and attenuated intestinal inflammation via inhibiting the TLR4/NF-κB signaling pathway. These findings suggested that EP-Zn exerted immunomodulatory and anti-inflammatory activities under physiological and inflammatory conditions, respectively.
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Antiinflamatorios , Polisacáridos , Ulva/química , Zinc , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Colon/efectos de los fármacos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Zinc/química , Zinc/farmacologíaRESUMEN
Water, even at trace concentrations, strongly increases the CO oxidation activities of the reducible metal oxide supported noble-metal catalysts, where the transfer of proton plays a key role. In this paper, we performed a thorough investigation of the interplay between water molecules and the reduced CeO2(111) surface. It was found that water molecules can induce the migration of oxygen vacancies which in turn results in the formation of surface protons. The proton then entangles with the near-surface polaron to form polaron-proton pair due to their mutual attractive interactions. The hopping of the polaron can easily trigger the long-range or short-range diffusion of protons mediated by water molecules at the CeO2(111) surface. These findings provide new insights into the key roles of oxygen vacancies and polarons in reducible oxide based heterogeneous catalysis, which is beneficial for the understanding of the increased activity of reducible oxide supported metal nanoparticles in the presence of water.
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Marine algae polysaccharides have been shown to regulate various biological activities, such as immune modulation, antioxidant, antidiabetic, and hypolipidemic. However, litter is known about the interaction of these polysaccharides with the gut microbiota. This study aimed to evaluate the effects of marine algae Enteromorpha (Ulva) prolifera polysaccharide (EP) supplementation on growth performance, immune response, and caecal microbiota of broiler chickens. A total of 200 1-day-old Ross-308 broiler chickens were randomly divided into two treatment groups with ten replications of ten chickens in each replication. The dietary treatments consisted of the control group (fed basal diet), and EP group (received diet supplemented with 400 mg EP/kg diet). Results showed that chickens fed EP exhibited significantly higher (P < 0.05) body weight and average daily gain than the chicken-fed basal diet. In addition, significantly longer villus height, shorter crypt depth, and higher villus height to crypt depth ratio were observed in the jejunal and ileal tissues of chickens fed EP. EP supplementation upregulated the mRNA expression of NF-κB, TLR4, MyD88, IL-2, IFN-α, and IL-1ß in the ileal and jejunal tissues (P < 0.05). Besides, we observed significantly higher (P < 0.05) short-chain volatile fatty acids (SCFAs) levels in the caecal contents of the EP group than in the control group. Furthermore, 16S-rRNA analysis revealed that EP supplementation altered gut microbiota and caused an abundance shift at the phylum and genus level in broiler chicken. Interestingly, we observed an association between microbiota and SCFAs production. Overall, this study demonstrated that supplementation of diet with EP promotes growth performance, improves intestinal immune response and integrity, and modulates the caecal microbiota of broiler chickens. This study highlighted the application of marine algae polysaccharides as an antibiotic alternative for chickens. Furthermore, it provides insight to develop marine algae polysaccharide-based functional food and therapeutic agent.
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The present study was conducted to evaluate the effects of 3 meals administered daily with varying dietary crude protein (CP) contents on hepatic lipid metabolism with a pig model. Pigs were divided into 3 groups according to the following feeding patterns: feeding a basal CP diet 3 times daily (3C); feeding a high CP diet for breakfast, the basal CP diet for lunch, and a low CP diet for dinner (HCL); and feeding the low CP diet for breakfast, the basal CP diet for lunch, and the high protein diet for dinner (LCH). Three groups took equivalent diet per meal ensuring that every pig was fed with similar dietary formulae daily. Results showed that HCL feeding pattern reduced the relative kidney weight (P < 0.05), and LCH feeding pattern increased the relative liver weight of pigs (P < 0.05) when compared with those in the 3C group. Plasma urea nitrogen (P < 0.01) and lipase (P < 0.05) decreased in the HCL group but increased in the LCH group. Both HCL and LCH feeding patterns reduced plasma triglycerides (P < 0.01), non-esterified fatty acids (NEFA) (P < 0.01), and hepatic crude fat (0.05 < P < 0.10) of pigs. Real-time quantitative PCR (RT-qPCR) results showed that dynamic feeding patterns down-regulated (P < 0.05) the mRNA level of lipid metabolism related genes, including adipose triglyceride lipase (ATGL), acetyl-CoA carboxylase (ACCα), liver X receptor (LXRα) in the liver, and negatively regulate elements of circadian clock, including period 1 (Per1), period 2 (Per2), cryptochrome (Cry2), which in turn, upregulated (P < 0.05) the protein expression of positive regulate element brain and muscle Arnt-like 1 (BMAL1) when compared with 3C group. Overall, our findings suggested that dynamic feeding patterns may affect hepatic lipid metabolism via regulation of the circadian clock.