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Meiosis is essential for generating genetic diversity and sexual spores, but the regulation of meiosis and ascosporogenesis is not clear in filamentous fungi, in which dikaryotic and diploid cells formed inside fruiting bodies are not free living and independent of pheromones or pheromone receptors. In this study, Gia1, a non-pheromone GPCR (G protein-coupled receptor) with sexual-specific expression in Fusarium graminearum, is found to be essential for ascosporogenesis. The gia1 mutant was normal in perithecium development, crozier formation, and karyogamy but failed to undergo meiosis, which could be partially rescued by a dominant active mutation in GPA1 and activation of the Gpmk1 pathway. GIA1 orthologs have conserved functions in regulating meiosis and ascosporogenesis in Sordariomycetes. GIA1 has a paralog, GIP1, in F. graminearum and other Hypocreales species which is essential for perithecium formation. GIP1 differed from GIA1 in expression profiles and downstream signaling during sexual reproduction. Whereas the C-terminal tail and IR3 were important for intracellular signaling, the N-terminal region and EL3 of Gia1 were responsible for recognizing its ligand, which is likely a protein enriched in developing perithecia, particularly in the gia1 mutant. Taken together, these results showed that GIA1 encodes a non-pheromone GPCR that regulates the entry into meiosis and ascosporogenesis via the downstream Gpmk1 MAP kinase pathway in F. graminearum and other filamentous ascomycetes.
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Ascomicetos , Fusarium , Triticum/microbiologia , Feromônios/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fusarium/genética , Ascomicetos/genética , Ascomicetos/metabolismo , Meiose/genética , Esporos FúngicosRESUMO
Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.
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Fenômenos Genéticos , Neoplasias , Humanos , Avaliação Pré-Clínica de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
BACKGROUND: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH. METHODS: A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro. RESULTS: Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1ß at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines. CONCLUSION: PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.
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Astrócitos , Fatores de Crescimento Neural , Doenças Neuroinflamatórias , Fator de Transcrição STAT1 , Serpinas , Hemorragia Subaracnóidea , Animais , Masculino , Ratos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Polaridade Celular , Células Cultivadas , Sistema de Sinalização das MAP Quinases , Fatores de Crescimento Neural/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Ratos Sprague-Dawley , Serpinas/metabolismo , Transdução de Sinais , Fator de Transcrição STAT1/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismoRESUMO
Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.
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Degeneração do Disco Intervertebral , Nanopartículas , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Gasderminas , Inflamassomos/metabolismo , Mitocôndrias/metabolismo , Polifenóis/farmacologiaRESUMO
Over the past decade, the use of photocatalysts (PCs) in controlled polymerization has brought new opportunities in sophisticated macromolecular synthesis. However, the selection of PCs in these systems has been typically based on laborious trial-and-error strategies. To tackle this limitation, computer-guided rational design of PCs based on knowledge of structure-property-performance relationships has emerged. These rational strategies provide rapid and economic methodologies for tuning the performance and functionality of a polymerization system, thus providing further opportunities for polymer science. This review provides an overview of PCs employed in photocontrolled polymerization systems and summarizes their progression from early systems to the current state-of-the-art. Background theories on electronic transitions are also introduced to establish the structure-property-performance relationships from a perspective of quantum chemistry. Typical examples for each type of structure-property relationships are then presented to enlighten future design of PCs for photocontrolled polymerization.
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Polímeros , Polimerização , Polímeros/químicaRESUMO
PURPOSE: To compare the clinical outcomes and radiographic outcomes of cortical bone trajectory (CBT) and traditional trajectory (TT) pedicle screw fixation in patients treated with single-level transforaminal lumbar interbody fusion (TLIF). METHODS: This trial included a total of 224 patients with lumbar spine disease who required single-level TLIF surgery. Patients were randomly assigned to the CBT and TT groups at a 1:1 ratio. Demographics and clinical and radiographic data were collected to evaluate the efficacy and safety of CBT and TT screw fixation in TLIF. RESULTS: The baseline characteristic data were similar between the CBT and TT groups. Back and leg pain for both the CBT and TT groups improved significantly from baseline to 24 months postoperatively. The CBT group experienced less pain than the TT group at one week postoperatively. The postoperative radiographic results showed that the accuracy of screw placement was significantly increased in the CBT group compared with the TT group (P < 0.05). The CBT group had a significantly lower rate of FJV than the TT group (P < 0.05). In addition, the rate of fusion and the rate of screw loosening were similar between the CBT and TT groups according to screw loosening criteria. CONCLUSION: This prospective, randomized controlled analysis suggests that clinical outcomes and radiographic characteristics, including fusion rates and caudal screw loosening rates, were comparable between CBT and TT screw fixation. Compared with the TT group, the CBT group showed advantages in the accuracy of screw placement and the FJV rate. CLINICAL TRIALS REGISTRATION: This trial has been registered at the US National Institutes of Health Clinical Trials Registry: NCT03105167.
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Parafusos Pediculares , Fusão Vertebral , Humanos , Parafusos Pediculares/efeitos adversos , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Osso Cortical/diagnóstico por imagem , Osso Cortical/cirurgia , Dor/etiologiaRESUMO
The photocatalyst (PC) zinc tetraphenylporphyrin (ZnTPP) is highly efficient for photoinduced electron/energy transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. However, ZnTPP suffers from poor absorbance of orange light by the so-called Q-band of the absorption spectrum (maximum absorption wavelength λmax = 600 nm, at which molar extinction coefficient εmax = 1.0×104 L/(mol·cm)), hindering photo-curing applications that entail long light penetration paths. Over the past decade, there has not been any competing candidate in terms of efficiency, despite a myriad of efforts in PC design. By theoretical evaluation, here we rationally introduce a peripheral benzo moiety on each of the pyrrole rings of ZnTPP, giving zinc tetraphenyl tetrabenzoporphyrin (ZnTPTBP). This modification not only enlarges the conjugation length of the system, but also alters the a1u occupied π molecular orbital energy level and breaks the accidental degeneracy between the a1u and a2u orbitals, which is responsible for the low absorption intensity of the Q-band. As a consequence, not only is there a pronounced hyperchromic and bathochromic effect (λmax = 655 nm and εmax = 5.2×104 L/(mol·cm)) of the Q-band, but the hyperchromic effect is achieved without increasing the intensity of the less useful, low wavelength absorption peaks of the PC. Remarkably, this strong 655 nm absorption takes advantage of deep-red (650-700 nm) light, a major component of solar light exhibiting good atmosphere penetration, exploited by the natural PC chlorophyll a as well. Compared with ZnTPP, ZnTPTBP displayed a 49% increase in PET-RAFT polymerization rate with good control, marking a significant leap in the area of photo-controlled polymerization.
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Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the bloodâbrain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the bloodâbrain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.
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Piroptose , Traumatismos da Medula Espinal , Camundongos , Animais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Lisossomos/metabolismo , Fosfolipases A2 Citosólicas/metabolismoRESUMO
Spinal cord injury (SCI) is a serious injury that can lead to irreversible motor dysfunction. Due to its complicated pathogenic mechanism, there are no effective drug treatments. Piperine, a natural active alkaloid extracted from black pepper, has been reported to influence neurogenesis and exert a neuroprotective effect in traumatic brain injury. The aim of this study was to investigate the therapeutic effect of piperine in an SCI model. SCI was induced in mice by clamping the spinal cord with a vascular clip for 1 min. Before SCI and every 2 days post-SCI, evaluations using the Basso mouse scale and inclined plane tests were performed. On day 28 after SCI, footprint analyses, and HE/Masson staining of tissues were performed. On a postoperative Day 3, the spinal cord was harvested to assess the levels of pyroptosis, reactive oxygen species (ROS), inflammation, and autophagy. Piperine enhanced functional recovery after SCI. Additionally, piperine reduced inflammation, oxidative stress, pyroptosis, and activated autophagy. However, the effects of piperine on functional recovery after SCI were reversed by autophagy inhibition. The study demonstrated that piperine facilitated functional recovery after SCI by inhibiting inflammatory, oxidative stress, and pyroptosis, mediated by the activation of autophagy.
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Alcaloides , Traumatismos da Medula Espinal , Camundongos , Animais , Piroptose , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Medula Espinal , Inflamação/tratamento farmacológico , Inflamação/patologia , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Estresse Oxidativo , AutofagiaRESUMO
The rapid urbanization and industrialization in China have led to an urgent dilemma for controlling urban air pollution, including the intensified emission of gasoline vapor into the atmosphere. Herein, we selected highland barley straw as a raw material and KOH and tetramethylammonium hydroxide (TMAOH) as activators to synthesize nitrogen-doped layered porous carbon (K-thAC) by a three-step activation method. The obtained K-thAC materials had a high specific surface area, reaching 3119 m2/g. Dynamic adsorption experiments demonstrated a superior adsorption capacity of up to 501 mg/g (K-thAC-25) for gasoline vapor compared with other documented carbon adsorbents. Moreover, adjusting the ratio of raw materials with a series of active ingredients could further improve the pore properties of the obtained K-thACs and their adsorption performance for gasoline vapor. Furthermore, the K-thAC materials were also characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), synchronous thermogravimetry (STA), X-ray powder diffraction (XRD), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and nitrogen adsorption tests. This study synthesized a novel plant-based material to treat gasoline vapor pollution efficiently.
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Metal naphthalocyanines (MNcs) were demonstrated to be efficient photocatalysts to activate photoinduced electron-transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, enabling well-controlled polymerization of (meth)acrylates under near-infrared (λ = 780 nm) light. Owing to their lower redox potential compared to previously explored photocatalysts, the activation of trithiocarbonate RAFT agents exhibited a unique selectivity that was dependent on the nature of the R group. Specifically, MNcs were capable in activating tertiary R group trithiocarbonates, whereas no activation of the trithiocarbonate possessing a secondary R group was observed. The combination of density functional theory calculations and experimental studies have revealed new mechanistic insights into the factors governing a PET-RAFT mechanism and explained this unique selectivity of MNcs toward tertiary carbon trithiocarbonates. Interestingly, by increasing the reaction temperature moderately (i.e., â¼15 °C), the energy barrier prohibiting the photoactivation of the trithiocarbonate with a secondary R group was overcome, enabling their successful activation.
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Clarifying the evolutionary processes underlying species diversification and adaptation is a key focus of evolutionary biology. Begonia (Begoniaceae) is one of the most species-rich angiosperm genera with c. 2000 species, most of which are shade-adapted. Here, we present chromosome-scale genome assemblies for four species of Begonia (B. loranthoides, B. masoniana, B. darthvaderiana and B. peltatifolia), and whole genome shotgun data for an additional 74 Begonia representatives to investigate lineage evolution and shade adaptation of the genus. The four genome assemblies range in size from 331.75 Mb (B. peltatifolia) to 799.83 Mb (B. masoniana), and harbor 22 059-23 444 protein-coding genes. Synteny analysis revealed a lineage-specific whole-genome duplication (WGD) that occurred just before the diversification of Begonia. Functional enrichment of gene families retained after WGD highlights the significance of modified carbohydrate metabolism and photosynthesis possibly linked to shade adaptation in the genus, which is further supported by expansions of gene families involved in light perception and harvesting. Phylogenomic reconstructions and genomics studies indicate that genomic introgression has also played a role in the evolution of Begonia. Overall, this study provides valuable genomic resources for Begonia and suggests potential drivers underlying the diversity and adaptive evolution of this mega-diverse clade.
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Begoniaceae , Begoniaceae/genética , Evolução Molecular , Genoma , Filogenia , Sintenia/genéticaRESUMO
First-order nonadiabatic coupling (NAC) matrix elements (fo-NACMEs) are the basic quantities in theoretical descriptions of electronically nonadiabatic processes that are ubiquitous in molecular physics and chemistry. Given the large size of systems of chemical interests, time-dependent density functional theory (TDDFT) is usually the first choice of methods. However, the lack of many-electron wave functions in TDDFT renders the formulation of NAC-TDDFT for fo-NACMEs conceptually difficult. Because of this, various variants of NAC-TDDFT have been proposed in the literature from different standing points, including the Hellmann-Feynman-like expression and auxiliary/pseudo-wave function (AWF)-, equation-of-motion (EOM)-, and time-dependent perturbation theory (TDPT)-based formulations. Based on critical analyses, the following conclusions are made here: (1) The Hellmann-Feynman-like expression, which is rooted in exact wave function theory, is hardly useful due to huge demand on basis sets. (2) Although most popular, the AWF variants of NAC-TDDFT are not theoretically founded and become ambiguous particularly for the fo-NACMEs between two excited states, although they do agree with the EOM and TDPT variants under the Tamm-Dancoff approximation. (3) The TDPT variant of NAC-TDDFT is theoretically most rigorous but suffers from numerical instabilities on the one hand and does not differ to a significant extent from the EOM variant on the other hand. (4) As such, the EOM variant of NAC-TDDFT for the fo-NACMEs between the ground and excited states and between two excited states is solely the right choice in practice. These formal analyses are fully supported by numerical experimentations, taking azulene as a showcase. The proper implementation of the EOM variant of NAC-TDDFT is also highlighted, showing that the fo-NACMEs between the ground and excited states and between two excited states are computationally very much the same as the analytic energy gradients of DFT and TDDFT, respectively. Possible future developments of the EOM variant of NAC-TDDFT are also highlighted. Its extensions to spin-adapted open-shell TDDFT and proper treatment of spin-orbit couplings (which are another source of force for electronically nonadiabatic processes) are particularly warranted in the near future.
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Random-pattern skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery; however, ischemia and subsequent ischemia-reperfusion injury lead to flap necrosis and are major complications. Exenatide, a glucagon-like peptide-1 analog, exerts therapeutic benefits for diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. Furthermore, Exenatide is a known activator of autophagy, which is a complex process of subcellular degradation that may enhance the viability of random skin flaps. In this study, we explored whether exenatide can improve skin flap survival. Our results showed that exenatide augments autophagy, increases flap viability, enhances angiogenesis, reduces oxidative stress, and alleviates pyroptosis. Coadministration of exenatide with 3-methyladenine and chloroquine, potent inhibitors of autophagy, reversed the beneficial effects, suggesting that the therapeutic benefits of exenatide for skin flaps are due largely to autophagy activation. Mechanistically, we identified that exenatide enhanced activation and nuclear translocation of TFE3, which leads to autophagy activation. Furthermore, we found that exenatide activates the AMPK-SKP2-CARM1 and AMPK-mTOR signaling pathways, which likely lead to exenatide's effects on activating TFE3. Overall, our findings suggest that exenatide may be a potent therapy to prevent flap necrosis, and we also reveal novel mechanistic insight into exenatide's effect on flap survival.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Exenatida/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pele , Pele/irrigação sanguínea , Adenina/análogos & derivados , Adenina/farmacologia , Adenilato Quinase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação para Baixo/efeitos dos fármacos , Edema/patologia , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/metabolismo , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
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Inflamação/prevenção & controle , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Triterpenos/uso terapêutico , Idoso , Animais , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação/complicações , Interleucina-1beta/efeitos adversos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Triterpenos/química , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The production of cereal crops is frequently affected by diseases caused by Fusarium graminearum and Magnaporthe oryzae, two devastating fungal pathogens. To improve crop resistance, many studies have focused on understanding the mechanisms of host defense against these two fungi individually. However, our knowledge of the common and different host defenses against these pathogens is very limited. RESULTS: In this study, we employed Brachypodium distachyon as a model for cereal crops and performed comparative transcriptomics to study the dynamics of host gene expression at different infection stages. We found that infection with either F. graminearum or M. oryzae triggered massive transcriptomic reprogramming in the diseased tissues. Numerous defense-related genes were induced with dynamic changes during the time course of infection, including genes that function in pattern detection, MAPK cascade, phytohormone signaling, transcription, protein degradation, and secondary metabolism. In particular, the expression of jasmonic acid signaling genes and proteasome component genes were likely specifically inhibited or manipulated upon infection by F. graminearum. CONCLUSIONS: Our analysis showed that, although the affected host pathways are similar, their expression programs and regulations are distinct during infection by F. graminearum and M. oryzae. The results provide valuable insight into the interactions between B. distachyon and two important cereal pathogens.
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Ascomicetos/fisiologia , Brachypodium/genética , Brachypodium/microbiologia , Fusarium/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Mapas de Interação de Proteínas/genéticaRESUMO
BACKGROUND: It is challenging to proceed thoracoscopic anatomic resection when encountering severe pleural adhesion or calcified peribronchial lymphadenopathy. Compared with multiple-port video-assisted thoracoscopic surgery (MP-VATS), how to overcome these challenges in single-port (SP-) VATS is still an intractable problem. In the present study, we reported the surgical results of chronic inflammatory lung disease and shared some useful SP-VATS techniques. METHODS: We retrospectively assessed the surgical results of chronic inflammatory lung disease, primarily bronchiectasis, and mycobacterial infection, at our institution between 2010 and 2018. The patients who underwent SP-VATS anatomic resection were compared with those who underwent MP-VATS procedures. We analyzed the baseline characteristics, perioperative data, and postoperative outcomes, and illustrated four special techniques depending on the situation: flexible hook electrocautery, hilum-first technique, application of Satinsky vascular clamp, and staged closure of bronchial stump method. RESULTS: We classified 170 consecutive patients undergoing thoracoscopic anatomic resection into SP and MP groups, which had significant between-group differences in operation time and overall complication rate (P = 0.037 and 0.018, respectively). Compared to the MP-VATS group, the operation time of SP-VATS was shorter, and the conversion rate of SP-VATS was relatively lower (3.1% vs. 10.5%, P = 0.135). The most common complication was prolonged air leakage (SP-VATS, 10.8%; MP-VATS, 2.9%, P = 0.045). CONCLUSIONS: For chronic inflammatory lung disease, certain surgical techniques render SP-VATS anatomic resection feasible and safe with a lower conversion rate.
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Pneumopatias , Neoplasias Pulmonares , Humanos , Pneumopatias/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Estudos Retrospectivos , Cirurgia Torácica VídeoassistidaRESUMO
The number of young people living in the margins of society reflects one of the most pressing social inequities of our time. Opportunity youth often face many complex challenges perpetrated by a range of systemic issues. These trajectories can be positively disrupted by surrounding youth with a cohesive web of relational and instrumental supports and spaces where their strengths and potential are seen. Opportunity Reboot, a technical assistance and program enhancement model, was developed to leverage the existing capacity and strengths of community programs to more effectively create pathways to school, career, and life success for opportunity youth. The impact of Opportunity Reboot was tested using a single-group, non-experimental design and a quasi-experimental design with propensity score matching. Findings established associations between opportunity youths' experiences of three core Opportunity Reboot features and growth in select positive identity, social-emotional competencies, and skills for systems navigation outcomes. Opportunity Reboot youth were also more likely, on average, than comparison youth to be employed in the four quarters after endline data collection; this finding was even stronger when comparing youth of color in the Opportunity Reboot and comparison groups. This evaluation strengthens the evidence that program enhancement models like Opportunity Reboot hold promise for positively disrupting the lives of opportunity youth.
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Instituições Acadêmicas , Habilidades Sociais , Adolescente , HumanosRESUMO
Covalent organic frameworks (COFs) with improved stability and extended π-conjugation structure are highly desirable. Here, two imine-linked COFs were converted into ultrastable and π-conjugated fused-aromatic thieno[3,2-c]pyridine-linked COFs (B-COF-2 and T-COF-2). The successful conversion was confirmed by infrared and solid-state 13C NMR spectroscopies. Furthermore, the structures of thieno[3,2-c]pyridine-linked COFs were evaluated by TEM and PXRD. It is noted that a slight difference in the structure leads to totally different photoactivity. The fully π-conjugated T-COF-2 containing triazine as the core exhibited an excellent photocatalytic NADH regeneration yield of 74% in 10 min.
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A laser-diode-based white lighting module is fabricated via spectral component optimization, which can achieve both high luminous flux and high color rendering index (CRI). In this work, the laser module is constituted by blue laser diodes (LDs) which excite YAG:Ce-Al2O3 and red LDs that can compensate for the lack of red spectrum to improve the CRI of the light source. To fulfill the requirements of flexibility and compactness of light source, the blue and red LDs beams are combined by optical fiber coupling. A simulation framework is employed to optimize the dominant wavelength of red LDs and the power ratio of red to blue LDs. According to the results of the integrating sphere, high luminous flux of 1102 lm and high CRI of 77.8 are achieved simultaneously, which is consistent with the simulation results. The tunable correlated color temperature (CCT) varying from 4000 K to 2800 K and high angular color uniformity (ACU) can be obtained.