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In this study, we synthesized and employed an ionic gel-functionalized silica stationary phase for high-performance liquid chromatography. The successful fabrication of the stationary phase was confirmed through attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), zeta-potential measurements, and elemental analysis (EA). Comparative performance evaluation against a commercial column demonstrated the prepared column's effectiveness in the mixed mode of reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), and ion chromatography (IC). Moreover, the stationary phase exhibited exceptional retention repeatability in per aqueous liquid chromatography, showcasing its potential as an environmentally friendly analytical method. Mechanistic investigations unveiled multiple solute-stationary phase interactions, including π-π interactions, hydrogen bonding, and ion exchange. Finally, we applied the developed stationary phase for the precise detection of preservatives in carbonated beverages and jelly, achieving high levels of accuracy and recovery rates.
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The bottom contact in perovskite solar cells (PSCs) is easy to cause deep trap states and severe instability issues, especially under maximum power point tracking (MPPT). In this study, sodium gluconate (SG) is employed to disperse tin oxide (SnO2) nanoparticles (NPs) and regulate the interface contact at the buried interface. The SG-SnO2 electron transfer layer (ETL) enabled the deposition of pinhole-free perovskite films in ambient air and improved interface contact by bridging effect. SG-SnO2 PSCs achieved an impressive power conversion efficiency (PCE) of 25.34% (certified as 25.17%) with a high open-circuit voltage (VOC) exceeding 1.19 V. The VOC loss is less than 0.34 V relative to the 1.53 eV bandgap, and the fill factor (FF) loss is only 2.02% due to the improved contact. The SG-SnO2 PSCs retained around 90% of their initial PCEs after 1000 h operation (T90 = 1000 h), higher than T80 = 1000 h for the control SnO2 PSC. Microstructure analysis revealed that light-induced degradation primarily occurred at the buried holes and grain boundaries and highlighted the importance of bottom-contact engineering.
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Goosecoid (GSC), translated from a homeobox gene, is a protein that participates in metastasis of various cancers. Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies associated with a poor diagnosis and prognosis. To develop new treatment target or biomarker for PAAD, this study intended to assess the effects and the molecular mechanism of GSC on PAAD metastasis. The expressive discrepancy of GSC in PAAD and normal tissues/cells was compared by both the quantitative PCR and western blot. The effects of GSC silencing and GSC over-expression on PAAD cells and TGF-ß signaling were proved by wound-healing assay, cell counting kit-8, Transwell assay and western blot. From the results, GSC mRNA and protein levels were enriched in PAAD cancer tissues and cells. GSC silencing prohibited metastasis of PAAD cells including the ability to invade, migrate and epithelial-mesenchymal transition (EMT), whereas GSC upregulation stimulated these cells behaviors above. GSC silencing reversed the effects on cellular processes induced by activation of the TGF-ß pathway. Furthermore, silencing of GSC postponed tumor growth in xenograft model. In summary, GSC was abundantly expressed in PAAD, which activated the TGF-ß pathway to enhance cell metastasis and tumor development.
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Adenocarcinoma , Transición Epitelial-Mesenquimal , Metástasis de la Neoplasia , Neoplasias Pancreáticas , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Humanos , Ratones , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Péptidos y Proteínas de Señalización Intercelular , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the gene encoding the galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme. Children with MPS IVA usually develop pectus carinatum, genu valgum, and multiple skeletal abnormalities. AIM: To establish a patient-derived induced pluripotent stem cell (iPSC) disease model to investigate the effects of two GALNS missense mutations. METHODS: The medical history and clinical manifestations of a patient with MPS IVA were first inspected. The effects of the identified GALNS mutations were predicted through bioinformatic analysis. iPSCs were then generated by using Sendai virus to introduce Yamanaka reprogramming factors to urinary cells isolated from the patient. The pluripotency, karyotypic integrity, genetic mutations, and differentiation ability of the iPSCs were tested. The effects of the GALNS mutations were further experimentally characterized using patient-derived cells. RESULTS: The patient exhibited a typical MPS IVA phenotype. Enzyme replacement therapy could not correct her skeletal abnormalities. GALNS c.485C>A (p.S162Y) and c.494G>T (p.C165F) mutations, inherited from her father and mother respectively, were identified in the patient. These two mutations were predicted to disturb the hydrophobic core of the GALNS catalytic domain. Patient-derived iPSCs were successfully generated, and further characterization indicated that the two missense mutations significantly diminished GALNS activity without affecting its amount at both the RNA and protein levels. CONCLUSIONS: We established a novel clinically relevant MPS IVA disease model that will be useful not only for investigating the pathogenic mechanisms of MPS IVA variants but also for drug screening and preclinical evaluation of novel therapies.
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Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive 'smart' dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a 'smart' drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.
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Cesium lead triiodide (CsPbI3) perovskites have garnered significant attention owing to their suitable bandgap for tandem silicon substrates and excellent chemical stability. However, γ-CsPbI3 prepared via low-temperature co-evaporation is limited by a narrow black phase processing window and random crystal orientation, hindering its optoelectronic performance and industrial applications. This study introduced trace amounts of methylammonium iodide (MAI) into the co-evaporation system, enhancing the crystallization process, promoting columnar grain growth, and stabilizing the γ-phase perovskite, resulting in films with improved structural integrity and reduced defect density. The optimal Pb/Cs ratio for achieving the best photoelectric performance shifted from 1:1 to 1.1:1 in the presence of MAI. Additionally, the incorporation of MAI allowed for more efficient longitudinal carrier transport, as evidenced by the enhanced photoluminescence (PL) intensity. The bandgap of CsPbI3 remained approximately at 1.7 eV before the δ-phase transition, ensuring suitability for photovoltaic applications. Ultimately, a photovoltaic device with 12% efficiency is achieved in the p-i-n structure without additional post-annealing of the CsPbI3 perovskite films, demonstrating the practical benefits of MAI incorporation.
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PURPOSE: The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis. METHOD: The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy. RESULT: A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis. CONCLUSION: Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.
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In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.
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Oxidación-Reducción , Urato Oxidasa , Ácido Úrico , Especificidad por Sustrato , Urato Oxidasa/química , Urato Oxidasa/metabolismo , Ácido Úrico/química , Ácido Úrico/metabolismo , Ácido Úrico/orina , Ligandos , Humanos , Níquel/química , Níquel/metabolismo , Sitios de Unión , Dominio Catalítico , Catálisis , Modelos Moleculares , Espectroscopía de Absorción de Rayos XRESUMEN
Sterigmatocystins and aflatoxins are a group of mycotoxins mainly isolated from fungi of the genera Aspergillus. Since the discovery of sterigmatocystins in 1954 and aflatoxins in 1961, many scholars have conducted a series of studies on their structural identification, synthesis and biological activities. Studies have shown that sterigmatocystins and aflatoxins have a wide range of biological activities such as antitumour, antibacterial, anti-inflammatory, antiplasmodial, etc. The sterigmatocystins and aflatoxins had been shown to be hepatotoxic and nephrotoxic in animals. This review attempts to give a comprehensive summary of progress on the chemical structural features, synthesis, and bioactivity of sterigmatocystins and aflatoxins reported from 1954 to April 2024. A total of 72 sterigmatocystins and 20 aflatoxins are presented in this review. This paper reviews the chemical diversity and potential activity and toxicity of sterigmatocystins and aflatoxins, enhances the understanding of sterigmatocystins and aflatoxins that adversely affect humans and animals, and provides ideas for their prevention, research and development.
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Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.
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Diferenciación Celular , Células Endoteliales , Células Madre Pluripotentes Inducidas , Hígado , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/citología , Hígado/metabolismo , Hígado/citología , Análisis de la Célula Individual/métodos , Células Cultivadas , Biomarcadores/metabolismo , Lipoproteínas LDL/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Myricetin (1), Quercetin (2), Kaempferol (3) and Kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO-LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV-vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p-π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator-activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased.
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BACKGROUND: The importance of building ventilation to protect health has been more widely recognized since the COVID-19 pandemic. Outdoor air ventilation in buildings dilutes indoor-generated air pollutants (including bioaerosols) and reduces resulting occupant exposures. Many countries and organizations have advisory guidelines or mandatory standards for minimum ventilation rates (VRs) to maintain indoor air quality (IAQ). Because directly measuring VRs is often difficult, many IAQ guidelines instead specify indoor concentration limits for carbon dioxide (CO2), using CO2 exhaled by building occupants as an indicator of VR. Although indoor CO2 guidelines are common, the evidence basis for the various CO2 limits has not been clear. OBJECTIVE: To review current indoor CO2 guidelines worldwide and the supportive evidence provided. METHODS: We identified worldwide CO2-based guidelines for IAQ or ventilation, along with any supportive evidence provided. We excluded occupational guidelines for CO2 levels ≥5000 ppm. RESULTS: Among 43 guidelines identified, 35 set single CO2 concentration limits and eight set multi-tiered limits; 16 mentioned no specific human effect to be controlled, 19 specified only odor dissatisfaction, five specified non-infectious health effects, and three specified airborne infectious disease transmission. The most common indoor CO2 limit was 1000 ppm. Thirteen guidelines specified maximum CO2 limits as extended time-weighted averages, none with evidence linking averaged limits to occupant effects. Of only 18 guidelines citing evidence to support limits set, we found this evidence persuasive for eight. Among these eight guidelines, seven set limits to control odor perception. One provided 17 scientifically-based CO2 limits, for specific example space uses and occupancies, to control long-range COVID-19 transmission indoors. IMPACT: Many current indoor carbon dioxide (CO2) guidelines for indoor air quality specified no adverse effects intended for control. Odor dissatisfaction was the effect mentioned most frequently, few mentioned health, and three mentioned control of infectious disease. Only one CO2 guideline was developed from scientific models to control airborne transmission of COVID-19. Most guidelines provided no supportive evidence for specified limits; few provided persuasive evidence. No scientific basis is apparent for setting one CO2 limit for IAQ across all buildings, setting a CO2 limit for IAQ as an extended time-weighted average, or using any arbitrary one-time CO2 measurement to verify a desired VR.
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Contaminación del Aire Interior , COVID-19 , Dióxido de Carbono , Guías como Asunto , SARS-CoV-2 , Ventilación , Contaminación del Aire Interior/análisis , Humanos , Dióxido de Carbono/análisis , Ventilación/normas , COVID-19/prevención & control , COVID-19/transmisión , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/normasRESUMEN
Unlike sedentary plant-parasitic nematodes, migratory plant endoparasitic nematodes (MPENs) are unable to establish permanent feeding sites, and all developmental stages (except eggs) can invade and feed on plant tissues and can be easily overlooked because of the unspecific symptoms. They cause numerous economic losses in agriculture, forestry, and horticulture. In order to understand the pathogenetic mechanism of MPENs, here we describe research on functions and host targets focused on currently identified effectors from six MPENs, namely Radopholus similis, Pratylenchus spp., Ditylenchus destructor, Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Hirschmanniella oryzae. This information will provide valuable insights into understanding MPEN effectors and for future fostering advancements in plant protection.
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Interacciones Huésped-Parásitos , Enfermedades de las Plantas , Plantas , Animales , Enfermedades de las Plantas/parasitología , Plantas/parasitología , Nematodos/patogenicidad , Proteínas del Helminto/metabolismoRESUMEN
Dye-sensitized solar cells (DSSCs), quantum dot-sensitized solar cells (QDSSCs) and perovskite solar cells (PSCs) have attracted wide attention. DSSCs, QDSSCs and PSCs can be prepared by liquid phase or solid phase, which causes a certain range of interface micro-mass changes during preparation. In addition, the photoelectric conversion process occurring inside the device also inevitably causes interface micro-mass changes. Interpretation of these interface micro-mass changes can help to optimize the cell structure, improve the stability and performance repeatability of the device, as well as directly or indirectly infer, track and predict the internal photoelectric conversion mechanism of the device. Quartz crystal microbalance (QCM) is a powerful tool for studying surface mass changes, extending this technology to the fields of solar cells to directly obtain interface micro-mass changes, which makes the research more in-depth and opens up a new perspective for explaining the basic principles of solar cells. This review summarizes the research progress of QCM application in DSSCs, QDSSCs and PSCs in recent years, and explores the challenges and new opportunities of QCM application in new solar cells in the future.
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Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti3C2Tx MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti3C2Tx-APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m-2 h-1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm2) evaporator, and the evaporation rate is further increased to 1.672 kg m-2 h-1 for a small-area (2 × 2 cm2) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h-1/$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene.
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Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.
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Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.
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Autofagia Mediada por Chaperones , Glucógeno Sintasa Quinasa 3 beta , Inflamación , Proteína 2 de la Membrana Asociada a los Lisosomas , Células Madre Mesenquimatosas , Osteogénesis , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , beta Catenina , Animales , Osteogénesis/fisiología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , beta Catenina/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Inflamación/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Transducción de Señal , Masculino , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Diferenciación Celular , Osteoclastos/metabolismoRESUMEN
The salt metathesis of a boryl-ethynyl lithium salt {[(HCDipN)2]B-CC-Li} with a monochlorosilylene [LSi(:)Cl; L = PhC(NtBu)2] produced an isolable boryl-ethynyl silylene {1; [(HCDipN)2]B-CîC-Si(L)}. The Si(II) center in 1 possesses a nonbonding lone pair and forms a covalent bond with the ethynyl group. The characterization of 1 was carried out by multinuclear NMR spectroscopy, single-crystal X-ray structure analysis and DFT calculations. Additionally, a reactivity study of 1 was conducted towards oxygen-containing and aryl C-F substrates.
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Sepsis is a systemic inflammatory response syndrome caused by trauma or infection, which can lead to multiple organ dysfunction. In severe cases, sepsis can also progress to septic shock and even death. Effective treatments for sepsis are still under development. This study aimed to determine if targeting the PI3K/Akt signaling with CAL-101, a PI3K p110δ inhibitor, could alleviate lipopolysaccharide (LPS)-induced sepsis and contribute to immune tolerance. Our findings indicated that CAL-101 treatment improved survival rates and alleviated the progression of LPS-induced sepsis. Compared to antibiotics, CAL-101 not only restored the Th17/regulatory T cells (Treg) balance but also enhanced Treg cell function. Additionally, CAL-101 promoted type 2 macrophage (M2) polarization, inhibited TNF-α secretion, and increased IL-10 secretion. Moreover, CAL-101 treatment reduced pyroptosis in peritoneal macrophages by inhibiting caspase-1/gasdermin D (GSDMD) activation. This study provides a mechanistic basis for future clinical exploration of targeted therapeutics and immunomodulatory strategies in the treatment of sepsis.
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Fosfatidilinositol 3-Quinasa Clase I , Ratones Endogámicos C57BL , Piroptosis , Sepsis , Linfocitos T Reguladores , Células Th17 , Animales , Ratones , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Piroptosis/efectos de los fármacos , Sepsis/inmunología , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/inmunología , Células Th17/efectos de los fármacosRESUMEN
Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss ( LSM ), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.