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To study the interspecific differentiation characteristics of species originating from recent radiation, the genotyping-by-sequencing (GBS) technique was used to explore the kinship, population structure, gene flow, genetic variability, genotype-environment association and selective sweeps of Picea asperata complex with similar phenotypes from a genome-wide perspective. The following results were obtained: 14 populations of P. asperata complex could be divided into 5 clades; P. wilsonii and P. neoveitchii diverged earlier and were more distantly related to the remaining 6 spruce species. Various geological events have promoted the species differentiation of P. asperata complex. There were four instances of gene flow among P. koraiensis, P. meyeri, P. asperata, P. crassifolia and P. mongolica. The population of P. mongolica had the highest level of nucleotide diversity, and P. neoveitchii may have experienced a bottleneck recently. Genotype-environment association found that a total of 20,808 genes were related to the environmental variables, which enhanced the adaptability of spruce in different environments. Genes that were selectively swept in the P. asperata complex were primarily associated with plant stress resistance. Among them were some genes involved in plant growth and development, heat stress, circadian rhythms and flowering. In addition to the commonly selected genes, different spruce species also displayed unique genes subjected to selective sweeps that improved their adaptability to different habitats. Understanding the interspecific gene flow and adaptive evolution of Picea species is beneficial to further understanding the species relationships of spruce and can provide a basis for studying spruce introgression and functional genomics.
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Ethane, the second most abundant gaseous hydrocarbon in vast anoxic environments, is an overlooked greenhouse gas. Microbial anaerobic oxidation of ethane can be driven by available electron acceptors such as sulfate and nitrate. However, despite nitrite being a more thermodynamically feasible electron acceptor than sulfate or nitrate, little is known about nitrite-driven anaerobic ethane oxidation. In this study, a microbial culture capable of nitrite-driven anaerobic ethane oxidation was enriched through the long-term operation of a nitrite-and-ethane-fed bioreactor. During continuous operation, the nitrite removal rate and the theoretical ethane oxidation rate remained stable at approximately 25.0 mg NO2 -N L-1 d-1 and 11.48 mg C2H6 L-1 d-1, respectively. Batch tests demonstrated that ethane is essential for nitrite removal in this microbial culture. Metabolic function analysis revealed that a species affiliated with a novel genus within the family Rhodocyclaceae, designated as 'Candidatus Alkanivoras nitrosoreducens', may perform the nitrite-driven anaerobic ethane oxidation. In the proposed metabolic model, despite the absence of known genes for ethane conversion to ethyl-succinate and succinate-CoA ligase, 'Ca. A. nitrosoreducens' encodes a prospective fumarate addition pathway for anaerobic ethane oxidation and a complete denitrification pathway for nitrite reduction to nitrogen. These findings advance our understanding of nitrite-driven anaerobic ethane oxidation, highlighting the previously overlooked impact of anaerobic ethane oxidation in natural ecosystems.
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High-permeability sand cannot control the water that is stored behind an embankment. In addition, if clay cannot be provided within a reasonable distance of the embankment construction site, an alternative method must be found. The study proposes using a polyurethane foam-sand mixture to construct an impermeable embankment. The main purpose of the paper was to predict the seismic stability of the embankment. The nonlinear finite element models (FEMs) are applied along with artificial neural networks (ANNs), and this research method applied was performed to investigate the main objectives of the research. Catastrophe theory was used to predict the mechanism of differential displacement in the Y direction at selected points of the embankment model. For model smooth functions, the basis spline (B-spline) method was applied to simulate the catastrophe progression index value. Results revealed that the suitability of the polyurethane foam-sand mixture controls the acceleration, displacement, strain, and stress of the model at points selected in different parts of the embankment. Moreover, it was found that the deformation pattern of the model was related to the polyurethane foam-sand mixture ratios. Furthermore, the main contribution was that the seismic response of the embankment model could be improved with the right percentage of polyurethane foam added to the sand. Results were validated by referencing those available in the literature.
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OBJECTIVES: To investigate the neurodevelopmental characteristics of children with autism spectrum disorder (ASD), analyze the correlation between neurodevelopmental indicators and cerebral blood flow (CBF), and explore the potential mechanisms of neurodevelopment in ASD children. METHODS: A retrospective study was conducted on 145 children aged 2-6 years with newly-diagnosed ASD. Scores from the Gesell Developmental Diagnosis Scale and the Autism Behavior Checklist (ABC) and CBF results were collected to compare gender differences in the development of children with ASD and analyze the correlation between CBF and neurodevelopmental indicators. RESULTS: Fine motor and personal-social development quotient in boys with ASD were lower than those in girls with ASD (P<0.05). Gross motor development quotient in ASD children was negatively correlated with CBF in the left frontal lobe (r=-0.200, P=0.016), right frontal lobe (r=-0.279, P=0.001), left parietal lobe (r=-0.208, P=0.012), and right parietal lobe (r=-0.187, P=0.025). The total ABC score was positively correlated with CBF in the left amygdala (r=0.295, P<0.001). CONCLUSIONS: Early intervention training should pay attention to gender and developmental structural characteristics for precise intervention in ASD children. CBF has the potential to become a biological marker for assessing the severity of ASD.
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Trastorno del Espectro Autista , Circulación Cerebrovascular , Humanos , Masculino , Trastorno del Espectro Autista/fisiopatología , Femenino , Preescolar , Niño , Estudios Retrospectivos , Desarrollo InfantilRESUMEN
Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME. It can cause high expression of IFN-γ, which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells. Therefore, combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense, leading to a collaborative anti-tumor outcome. Thus, utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites, thereby reshaping immunosuppressive TME for cancer treatment, has great potential as an immunogene therapy in clinical applications.
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To control the diffusion of high concentrations of coal dust during tunnel boring and minimize the threat to the life and health of coal miners, theoretical analysis, numerical simulations, and field measurements were combined in this study. First, computational fluid dynamic simulation software was used to simulate the generation of dust particles and their transport pattern in the tunnel. Subsequently, an innovative orthogonal test was performed to study the effect of four ventilation parameters [the pressure airflow rate (Q), distance between the air duct center and heading face (LA), distance between the air duct center and tunnel floor (LB), and distance between the air duct center and nearest coal wall (LC)] on dust diffusion. According to the orthogonal test results, the optimal ventilation parameters for effective dust control are as follows: Q = 1400 m3/min, LA = 7 m, LB = 2.8 m, and LC = 1 m. The optimized set of ventilation parameters was applied to the Wangpo 3206 working face. The results show that dust diffusion in the tunnel was effectively controlled and that the air quality was sufficiently improved.
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Carbón Mineral , Polvo , Ventilación , Contaminación del Aire/prevención & control , Hidrodinámica , Simulación por Computador , Minas de Carbón , HumanosRESUMEN
Heavy metal pollution is a global environmental problem, and Quercus variabilis has a stronger tolerance to Cd stress than do other species. We aimed to explore the physiological response and molecular mechanisms of Q. variabilis to Cd stress. In this study, the antioxidant enzyme activities of leaves were determined, while the photosynthetic parameters of leaves were measured using Handy PEA, and ion fluxes and DEGs in the roots were investigated using noninvasive microtest technology (NMT) and RNA sequencing techniques, respectively. Cd stress at different concentrations and for different durations affected the uptake patterns of Cd2+ and H+ by Q. variabilis and affected the photosynthetic efficiency of leaves. Moreover, there was a positive relationship between antioxidant enzyme (CAT and POD) activity and Cd concentration. Transcriptome analysis revealed that many genes, including genes related to the cell wall, glutathione metabolism, ion uptake and transport, were significantly upregulated in response to cadmium stress in Q. variabilis roots. WGCNA showed that these DEGs could be divided into eight modules. The turquoise and blue modules exhibited the strongest correlations, and the most significantly enriched pathways were the phytohormone signaling pathway and the phenylpropanoid biosynthesis pathway, respectively. These findings suggest that Q. variabilis can bolster plant tolerance by modulating signal transduction and increasing the synthesis of compounds, such as lignin, under Cd stress. In summary, Q. variabilis can adapt to Cd stress by increasing the activity of antioxidant enzymes, and regulating the fluxes of Cd2+ and H+ ions and the expression of Cd stress-related genes.
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Cadmio , Regulación de la Expresión Génica de las Plantas , Quercus , Estrés Fisiológico , Quercus/metabolismo , Quercus/efectos de los fármacos , Quercus/genética , Cadmio/toxicidad , Cadmio/metabolismo , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Fotosíntesis/efectos de los fármacos , Antioxidantes/metabolismoRESUMEN
The coupling between anammox and nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) has been considered a sustainable technology for nitrogen removal from sidestream wastewater and can be implemented in both membrane biofilm reactor (MBfR) and granular bioreactor. However, the potential influence of the accompanying hydrogen sulfide (H2S) in the anaerobic digestion (AD)-related methane-containing mixture on anammox/n-DAMO remains unknown. To fill this gap, this work first constructed a model incorporating the C/N/S-related bioprocesses and evaluated/calibrated/validated the model using experimental data. The model was then used to explore the impact of H2S on the MBfR and granular bioreactor designed to perform anammox/n-DAMO at practical levels (i.e., 0â¼5% (v/v) and 0â¼40 g/S m3, respectively). The simulation results indicated that H2S in inflow gas did not significantly affect the total nitrogen (TN) removal of the MBfR under all operational conditions studied in this work, thus lifting the concern about applying AD-produced biogas to power up anammox/n-DAMO in the MBfR. However, the presence of H2S in the influent would either compromise the treatment performance of the granular bioreactor at a relatively high influent NH4+-N/NO2--N ratio (e.g., >1.0) or lead to increased energy demand associated with TN removal at a relatively low influent NH4+-N/NO2--N ratio (e.g., <0.7). Such a negative effect of the influent H2S could not be attenuated by regulating the hydraulic residence time and should therefore be avoided when applying the granular bioreactor to perform anammox/n-DAMO in practice.
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Reactores Biológicos , Sulfuro de Hidrógeno , Metano , Nitratos , Nitritos , Oxidación-Reducción , Sulfuro de Hidrógeno/metabolismo , Anaerobiosis , Metano/metabolismo , Nitratos/metabolismo , Eliminación de Residuos Líquidos/métodos , Nitrógeno/metabolismo , Aguas Residuales/químicaRESUMEN
The taxonomic classification of Picea meyeri and P. mongolica has long been controversial. To investigate the genetic relatedness, evolutionary history, and population history dynamics of these species, genotyping-by-sequencing (GBS) technology was utilized to acquire whole-genome single nucleotide polymorphism (SNP) markers, which were subsequently used to assess population structure, population dynamics, and adaptive differentiation. Phylogenetic and population structural analyses at the genomic level indicated that although the ancestor of P. mongolica was a hybrid of P. meyeri and P. koraiensis, P. mongolica is an independent Picea species. Additionally, P. mongolica is more closely related to P. meyeri than to P. koraiensis, which is consistent with its geographic distribution. There were up to eight instances of interspecific and intraspecific gene flow between P. meyeri and P. mongolica. The P. meyeri and P. mongolica effective population sizes generally decreased, and Maxent modeling revealed that from the Last Glacial Maximum (LGM) to the present, their habitat areas decreased initially and then increased. However, under future climate scenarios, the habitat areas of both species were projected to decrease, especially under high-emission scenarios, which would place P. mongolica at risk of extinction and in urgent need of protection. Local adaptation has promoted differentiation between P. meyeri and P. mongolica. Genotypeâenvironment association analysis revealed 96,543 SNPs associated with environmental factors, mainly related to plant adaptations to moisture and temperature. Selective sweeps revealed that the selected genes among P. meyeri, P. mongolica and P. koraiensis are primarily associated in vascular plants with flowering, fruit development, and stress resistance. This research enhances our understanding of Picea species classification and provides a basis for future genetic improvement and species conservation efforts.
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Genoma de Planta , Picea , Polimorfismo de Nucleótido Simple , Dinámica Poblacional , Picea/genética , Filogenia , Flujo Génico , Adaptación Fisiológica/genética , EcosistemaRESUMEN
An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20â°C to 37â°C (optimum 30â°C). The major cellular fatty acids were C14â:â0, C16â:â1ω7c/C16â:â1ω6c and C16â:â1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64â% 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5â%, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.
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Methylococcaceae , Methylomonas , Metano , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , Ácidos Grasos/química , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Bacterias , Methylococcaceae/genética , Oxidación-ReducciónRESUMEN
Aerobic methanotrophs establish a symbiotic association with denitrifiers to facilitate the process of aerobic methane oxidation coupled with denitrification (AME-D). However, the symbiosis has been frequently observed in hypoxic conditions continuing to pose an enigma. The present study has firstly characterized an electrically induced symbiosis primarily governed by Methylosarcina and Hyphomicrobium for the AME-D process in a hypoxic niche caused by Comammox Nitrospira. The kinetic analysis revealed that Comammox Nitrospira exhibited a higher apparent oxygen affinity compared to Methylosarcina. While the coexistence of comammox and AME-D resulted in an increase in methane oxidation and nitrogen loss rates, from 0.82 ± 0.10 to 1.72 ± 0.09 mmol CH4 d-1 and from 0.59 ± 0.04 to 1.30 ± 0.15 mmol N2 d-1, respectively. Furthermore, the constructed microbial fuel cells demonstrated a pronounced dependence of the biocurrents on AME-D due to oxygen competition, suggesting the involvement of direct interspecies electron transfer in the AME-D process under hypoxic conditions. Metagenomic and metatranscriptomic analysis revealed that Methylosarcina efficiently oxidized methane to formaldehyde, subsequently generating abundant NAD(P)H for nitrate reduction by Hyphomicrobium through the dissimilatory RuMP pathway, leading to CO2 production. This study challenges the conventional understanding of survival mechanism employed by AME-D symbionts, thereby contributing to the characterization responsible for limiting methane emissions and promoting nitrogen removal in hypoxic regions.
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Metano , Nitrógeno , Oxígeno , Simbiosis , Nitrógeno/metabolismo , Metano/metabolismo , Oxígeno/metabolismo , Oxidación-Reducción , DesnitrificaciónRESUMEN
The use of surfactants is crucial for the prevention and control of coal dust pollution in coal mining operation areas, yet there still exist many challenges in the control of coal dust pollution. In this paper, the green biomass-based amino acid surfactant sodium myristoyl glutamate (SMG) and the anionic surfactant sodium α-alkenyl sulfonate (AOS) were selected to investigate the improvement of coal dust wettability by single and binary solutions from the macroscopic and microscopic perspectives. Molecular simulations were used to reveal the microscopic mechanism of the wettability of coal dust by the different solutions. Experimental measurements showed that the contact angle of the AOS + SMG aqueous solution was as low as 13.8° on a coal surface. Coating the coal dust with the AOS + SMG solution reduced the surface tension by 12.02% compared to coating the coal with a single component solution. Additionally, the use of the binary AOS + SMG solution increased the hydrophilic group content in the coating by 11.77% compared to a single component solution, and the linkage between hydrophilic groups was enhanced, which pulls the water molecules to wet the coal dust. These research results should provide a new way to promote more environmentally friendly coal dust pollution control technology.
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Carbón Mineral , Polvo , Tensoactivos , Polvo/análisis , Tensoactivos/química , Aminoácidos/química , Humectabilidad , Alcanosulfonatos/química , Minas de Carbón , Contaminación Ambiental/prevención & controlRESUMEN
'Candidatus Methanoperedens nitroreducens' is an archaeal methanotroph with global importance that links carbon and nitrogen cycles and great potential for sustainable operation of wastewater treatment. It has been reported to mediate the anaerobic oxidation of methane through a reverse methanogenesis pathway while reducing nitrate to nitrite. Here, we demonstrate that 'Ca. M. nitroreducens' reduces ferric iron forming ammonium (23.1 %) and nitrous oxide (N2O, 46.5 %) from nitrate. These results are supported with the upregulation of genes coding for proteins responsible for dissimilatory nitrate reduction to ammonium (nrfA), N2O formation (norV, cyt P460), and multiple multiheme c-type cytochromes for ferric iron reduction. Concomitantly, an increase in the N2O-reducing SJA-28 lineage and a decrease in the nitrite-reducing 'Candidatus Methylomirabilis oxyfera' are consistent with the changes in 'Ca. M. nitroreducens' end products. These findings demonstrate the highly flexible physiology of 'Ca. M. nitroreducens' in anaerobic ecosystems with diverse electron acceptor conditions, and further reveals its roles in linking methane oxidation to global biogeochemical cycles. 'Ca. M. nitroreducens' could significantly affect the bioavailability of nitrogen sources as well as the emission of greenhouse gas in natural ecosystems and wastewater treatment plants.
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Compuestos de Amonio , Metano , Nitratos , Óxido Nitroso , Oxidación-Reducción , Metano/metabolismo , Óxido Nitroso/metabolismo , Compuestos de Amonio/metabolismo , Anaerobiosis , Nitratos/metabolismo , Compuestos Férricos/metabolismoRESUMEN
The increasing level of mechanization in coal mining means more dust and gas are generated during excavation operations in tunnels. The high concentrations of dust and gas severely affect production efficiency and the physical and mental health of workers. Here, Ansys Fluent simulations were performed to derive the spatiotemporal evolution of coupled airflow-dust-gas diffusion in a low-gas excavation face. The aim was to optimize pollution control by determining the optimal duct distance, L, from the working face in the excavation tunnel. Our results showed that the airflow field affects the coupled diffusion and transport of dust and gas. According to a comparison of the effects of different duct distances from the working face, when L = 6 m, the average dust concentration in the tunnel is low (257.6 mg/m3), and the average gas concentration in the tunnel is 0.28 %, which does not exceed the safety limit. Accordingly, the optimal distance of the duct for pollution control is 6 m. The results of field measurements supported the validity of the simulation. Our findings can be used to improve the air quality in tunnels, thereby keeping miners safe and the working area clean.
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We report a case of skin dilator combined with titanium mesh to repair scalp and skull defects. An 18-year-old male with a scalp defect and skull necrosis due to high-voltage electrical burns was admitted to our hospital. In the first stage, the wound was debrided, antibiotics were applied to control the infection, and two skin dilators were embedded under the scalp after debridement. In the second stage, necrotic skull material was removed, the skull defect was repaired using titanium mesh, and the scalp defect was repaired by transferring expanded flaps. The patient was followed up for 6 months, recovering well and achieving a satisfactory head shape.
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Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Infarto del Miocardio , Ratas , Animales , Infarto del Miocardio/patología , Células Madre/patología , Esferoides Celulares/patología , Cicatrización de HeridasRESUMEN
This study aimed to probe the bioavailability of myofibrillar protein (MP) gels in mice as affected by incorporating anionic xanthan (XMP) and sodium alginate (SMP)/cationic chitosan (CSMP)/neutral curdlan (CMP) and konjac (KMP), respectively. The results showed that the numbers of peptides absorbed were obviously higher in anionic XMP and SMP groups (88 and 126, respectively) than in the cationic CSMP (51) group. The contents of free amino acids absorbed in SMP and XMP were significantly greater than that in CSMP and CMP groups (P < 0.05). Furthermore, the antioxidant capacity of bioactive compounds absorbed in the SMP group was higher than those in the other groups (P < 0.05), and the expression of tight junction protein (Occludin and ZO-1) was up-regulated in SMP group. The low contents of free ammonia, indole and p-cresol were observed in the anionic XMP, SMP and neutral KMP groups, compared to CSMP group. This work highlights the benefits of anionic polysaccharides (sodium alginate and xanthan) in developing low-fat meat products with high MP bioavailability.
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Carne de Cerdo , Carne Roja , Porcinos , Animales , Ratones , Disponibilidad Biológica , Polisacáridos/química , Alginatos , Geles/químicaAsunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Actinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genéticaRESUMEN
Immunotherapy has achieved prominent clinical efficacy in combating cancer and has recently become a mainstream treatment strategy. However, achieving broad efficacy with a single modality is challenging, and the heterogeneity of the tumor microenvironment (TME) restricts the accuracy and effectiveness of immunotherapy strategies for tumors. Herein, a TME-responsive targeted nanoparticle to enhance antitumor immunity and reverse immune escape by codelivering interleukin-12 (IL-12) expressing gene and colony-stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (PLX) is presented. The introduction of disulfide bonds and cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) peptides conferred reduction reactivity and tumor targeting to the nanoparticles, respectively. It is hypothesized that activating host immunity by the local expression of IL-12, while modulating the tumor-associated macrophages (TAM) function through blocking CSF-1/CSF-1R signaling, could constitute a feasible approach for cancer immunotherapy. The fabricated functional nanoparticle successfully ameliorated the TME by stimulating the proliferation and activation of T lymphocytes, promoting the repolarization of TAMs, reducing myeloid-derived suppressor cells (MDSCs), and promoting the maturation of dendritic cells (DC) as well as the secretion of antitumor cytokines, which efficiently suppressed tumor growth and metastasis. Finally, substantial changes in the TME were deciphered by single-cell analysis including infiltration of different cells, transcriptional states, secretory signaling and cell-cell communications. These findings provide a promising combinatorial immunotherapy strategy through immunomodulatory nanoparticles.
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Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Inmunoterapia , Macrófagos/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Interleucina-12/metabolismo , Nanopartículas/química , Línea Celular TumoralRESUMEN
Usnic acid has a variety of biological activities, and has been widely studied in the fields of antibacterial, immune stimulation, antiviral, antifungal, anti-inflammatory and antiparasitic. Based on this, usnic acid is used as the lead compound for structural modification. In order to enhance the biological activity and solubility of usnic acid, scholars have carried out a large number of structural modifications, and found some usnic acid derivatives to be of more potential research value. In this paper, the structural modification, biological activity and structure-activity relationship of usnic acid were reviewed to provide reference for the development of usnic acid derivatives.